#GENE	HGNC ID	ENTREZ GENE ID	CONDITION	INHERITANCE	AGE GROUP	ALLELIC CONDITIONS	MANIFESTATION CATEGORIES	INTERVENTION CATEGORIES	COMMENTS	INTERVENTION/RATIONALE	REFERENCES
A2M	7	2	Alpha-2-macroglobulin deficiency	AD	N/A	N/A	General	General	Variants have been implicated in pulmonary disease, but the evidence appears mixed	The clinical consequences of variants are unclear	94459; 2475424; 1370808 
A4GALT	18149	53947	Blood group, P system	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	10993874
AAAS	13666	8086	Achalasia-addisonianism-alacrimia syndrome	AR	Pediatric		Dermatologic; Endocrine; Gastrointestinal; Neurologic; Ophthalmologic	Endocrine		Surveillance and treatment/preventive measures (with substitution therapy) to avoid sequelae of adrenal insufficiency, including adrenal crisis , may be beneficial	78049; 6243664; 3565479; 1537368; 8006362; 7895750; 8757578; 11062474; 11159947; 11914417; 12429595; 12752575; 16264411; 16938764; 8628786; 19172511; 18172684; 20051279; 20200814; 20499090; 20447142; 21565631 
AAGAB	25662	79719	Keratoderma, palmoplantar, punctate type IA	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23000146; 23064416
AARS	20	16	Charcot-Marie-Tooth disease, axonal, type 2N	AD	N/A	N/A	Audiologic/Otolaryngologic; Neurologic	General	The condition can include hearing loss, which is described as postlingual	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20045102; 22206013; 22009580; 22573628
AARS2	21022	57505	Leukoencephalopathy, progressive, with ovarian failure	AR	Pediatric	Allelic with Combined oxidative phosphorylation deficiency 8 (AR)	Biochemical; Cardiovascular; Endocrine; Musculoskeletal; Neurologic; Obstetric	Obstetric		Females with may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desired	21549344; 24808023; 25058219
AASS	17366	10157	Hyperlysinemia	AR	N/A	N/A	Biochemical	General	Other than increased serum lysine, the evidence of a common phenotype is unclear, and there does not appear to be evidence that measures such as protein restriction or other metabolic treatments are effective	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14209691; 5796356; 5557172; 934735; 10775527; 23570448
ABAT	23	18	GABA-transaminase deficiency	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6148708; 4020531; 10407778
ABCA1	29	19	ABCA1 deficiency; Tangier disease; HDL deficiency, type 2	AR	Pediatric	Allelic with Familial hypoalphalipoproteinemia (AD)	Cardiovascular; Neurologic; Ophthalmologic	Cardiovascular	Familial hypoalphalipoproteinemia (HDL deficiency, type 2) may involve increased risk of cardiovascular disease	Early cardiovascular events are common (eg, myocardial infarctions due to atherosclerosis), and while specific medical therapy is not currently available, preventive measures to decrease additional contributory atherosclerotic risk factors, as well as surveillance to allow early diagnosis and treatment of cardiovascular manifestations, may be beneficial	14162531; 5831900; 4165386; 4165172; 198431; 190272; 194920; 195100; 75948; 7406376; 4082916; 3677505; 3799433; 3314502; 8432861; 7627690; 10431237; 10431236; 10525055; 9888879; 10533863; 16343506; 10535983;  10431238; 11086027; 11476965; 12084722; 12111371; 12111381; 12702168; 14742612; 16343506; 18955690; 19723515; 22179783; 22913675; 23430904
ABCA12	14637	26154	Ichthyosis, harlequin; Ichthyosis, lamellar, type 2	AR 	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8204475; 12208260; 12915478; 16007253; 15756637; 16902423; 21339420; 21729033; 22257947 
ABCA3	33	21	Surfactant metabolism dysfunction, pulmonary, 3; Interstitial lung disease	AD/AR	Pediatric		Pulmonary	Pulmonary		Individuals may present in infancy with severe respiratory insufficiency (a presentation in early childhood ascribed to a heterozygous mutation has also beeen described), and diagnosis has important therapeutic implications, as BMT can be effective; Lung transplant may be beneficial in some individuals	15044640; 15976379; 15819986; 15985750; 17719949; 22337229; 22304854; 23166334  
ABCA4	34	24	Cone-rod dystrophy 3; Retinitis pigmentosa 19; Stargardt disease 1; Retinal dystrophy, early-onset severe; Fundus flavimaculatus	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9054934; 9466990; 9425888; 9781034; 10442900; 10874631; 10396622; 11818392; 12515255; 12796258; 16896346; 16682602; 11385708; 21510770; 21786275; 22229821; 22312191; 22328824; 22395892; 22661473; 22863181; 23096905 
ABCB1	40	5243	Colchicine metabolism, association with	AD	Pediatric		General	Pharmacogenomic		Selection and dosing of medications (eg,colchicine) may be affected by the presence of variants	7188928; 7129432; 17259950; 18973929; 21851199
ABCB11	42	8647	Cholestasis, progressive familial intrahepatic 2	AD/AR	Pediatric	Allelic with Cholestasis, benign recurrent intrahepatic, 2 (AR)	Gastrointestinal; Oncologic	Gastrointestinal; Oncologic	The condition may involve multiple interacting variants	In severe forms, specific nutritional care may be beneficial (eg, including specific vitamin E supplementation); Individuals are at high risk for hepatocellular carcinoma early in life, and surveillance and early treatment may be beneficial; Recurrence after liver transplant may benefit from immunosuppresive treatment; Liver transplant may be indicated	9806540; 10579978; 15300568; 16039748; 16871584; 20301474; 19797282; 21055686; 21766090; 21219577; 22675952 
ABCB4	45	5244	Cholestasis, progressive familial intrahepatic 3; Low phospholipid-associated cholelithiasis 1;  Cholestasis, oral contraceptives induced; Cholestasis, familial intrahepatic, of pregnancy; Gallbladder disease 1	AD/AR	Pediatric		Gastrointestinal	Gastrointestinal; Obstetric; Pharmacogenomic	Heterozygous mutations reported in Cholestasis, progressive familial intrahepatic 3 are associated with other related conditions such as Intrahepatic cholestasis of pregnancy	Medical treatment (eg, with ursodeoxycholine) may be beneficial, though in some forms, liver transplantation has been described as necessary; Medications (eg, OCPs) may lead to adverse reactions; In pregnancy, the condition can cause severe sequelae (including death) in the fetus, as well as adverse maternal health outcomes, and precautions, including early delivery, may be beneficial	8666348; 9049190; 9419367; 9923886; 10767346; 11313315; 11313316; 15203080; 17726488; 17414143; 18482588; 19584064; 20887599; 20537830; 21310683; 21119540; 21989363
ABCB6	47	10058	Blood group, Langereis system	BG	Pediatric	Allelic with Dyschromatosis universalis hereditaria (AD); Familial pseudohyperkalemia (AD); Microphthalmia, isolated, with coloboma 7 (AD)	Dermatologic; Hematologic; Ophthalmologic	General; Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion); In Microphthalmia, isolated, with coloboma 7, genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5790273; 22246506; 22226084; 23180570; 23519333
ABCB7	48	22	Anemia, sideroblastic, and spinocerebellar ataxia	XL	N/A	N/A	Hematologic; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4045952; 10196363; 20301496; 22398176 
ABCC11	14639	85320	Apocrine gland secretion, variation in	AR	N/A	N/A	Dermatologic	General		The clinical relevance is unclear	16444273; 19710689
ABCC2	53	1244	Dubin-Johnson syndrome	AD/AR	N/A	N/A	Gastrointestinal	General	Heterozygotes may display manifestations; The presence of variants may have pharmacogenomic implications	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13193360; 5926936; 5532959; 520367; 2035335; 8621134; 9425227; 16952291; 16863439; 16549534; 19881259; 21044052; 22955427; 23007012; 23069858; 23115734 
ABCC6	57	368	Pseudoxanthoma elasticum	AD/AR/Digenic	Pediatric	Allelic with Generalized calcification of infancy, 2 (AR)	Cardiovascular; Dermatologic; Hematologic; Ophthalmologic	Cardiovascular; Hematologic; Ophthalmologic	In "recessive" forms, heterozygotes may have mild manifestations; Digenic inheritance (with GGCX) has been reported	Preventive measures (eg, weight control, avoidance of smoking, and medical management of hypertension and hypercholesterolemia) related to cardiovascular risk factors may be beneficial by decreasing contributory factors related to atherosclerosis; Awareness may allow surveillance for and early detection and treatment of  cardiovascular (eg, surgical interventions related to vascular disease) and hematologic manifestations (eg, interventions related to GI bleeding); Standard treatment for macular degeneration (including intraocular injection of anti-angiogenic drugs) may be beneficial, and awareness of ophthalmologic aspects may allow early detection and treatment; Circumstances such as contact sports and the use of medications that increase the risk of GI bleeding should be avoided	14068068; 3652487; 3342167; 2012127; 1600795; 8413390; 10619263; 10835643; 10835642; 10811882; 11209132; 15098239; 16086317; 18157818; 18800149; 19298904;  20034067; 20075945; 20301292; 21210805; 21386758; 21671388; 22209248; 23675997; 23746223; 23935882; 23968982; 23978319; 24008425
ABCC8	59	6833	Diabetes mellitus, transient neonatal, 2; Diabetes, permanent neonatal; Hyperinsulinemic hypoglycemia, familial, 1; Hypoglycemia, leucine-induced	AD/AR	Pediatric		Endocrine	Endocrine	Hyperinsulinemic hypoglycemia, familial, 1 inheritance may involve imprinting	Prompt treatment (eg, of ketoacidosis and dehydration) can avoid morbidity; Individuals with neonatal diabetes mellitus may respond well to sulfonylurea treatment; Non-neonatally affected individuals may respond to diazoxide; Individuals with leucine-induced hypoglycemia may have episodes triggered by high-protein (high leucine)  feedings, and may respond to diazoxide	7847376; 7716548; 923011; 8751851; 9727845; 10426386; 10322395; 11808881; 10334322; 1018078; 12559865; 12941782; 15356046; 15579781; 16885549; 16882742; 16613899; 8596924; 19254908; 20301620; 21716120; 23273570
ABCC9	60	10060	Cardiomyopathy, dilated, 10; Atrial fibrillation, familial 12; Cantu syndrome	AD	Pediatric		Cardiovascular; Dermatologic; Musculoskeletal	Cardiovascular	Though manifestations have been described in adults, surveillance and interventions should likely begin in the pediatric period	Surveillance for related cardiac complications, which have been reported to include cardiomyopathy and arrhythmias, may allow early medical intervention, decreasing  morbidity and mortality; Cantu syndrome, which may be clinically recognizable,  can include cardiovascular malformations that would benefit from surveillance/intervention similar to other ABCC9-related disorders	15034580; 16563363; 17245405; 22610116; 22608503 
ABCD1	61	215	Adrenoleukodystrophy	XL	Pediatric		Biochemical; Endocrine; Neurologic	Biochemical		For individuals with adrenal insufficiency, corticosteroid treatment is indicated; In asymptomatic individuals with ALD, treatment with "Lorenzo's oil" (oleic and erucic acids) may be beneficial in combination with dietary measures, though the benefit of such treatment in other affected individuals, such as symptomatic individuals, may not warrant such treatment ; BMT/HSCT has been reported as effective if performed early	169765; 61263; 965973; 200861; 200862; 218453; 7438498; 7436359; 6299222; 7202134; 6280106; 6387532; 2682348; 2309698; 7904210; 8094785; 8338333; 8441467; 7849723; 8040304; 7581394; 7825602; 8566952; 8636252; 9062496; 9183487; 10073906; 9894883; 11748843; 11085690;  11204280; 11916318; 11220738; 12210797; 12486501; 12913200; 15073029; 15812458; 16240348; 15668429; 16305618; 16380594; 16009761; 16313334; 17372139; 17353371; 18759549; 19892975; 20301491 
ABCD3	67	5825	Zellweger syndrome	AR	N/A	N/A	Biochemical; Craniofacial; Neurologic	General	The pathogenesis of variants are considered unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1301993; 9199576; 10447258; 17092750 
ABCD4	68	5826	Methylmalonic aciduria and homocystinuria, cblJ type	AR	Pediatric		Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Neurologic	Allergy/Immunology/Infectious; Biochemical; Cardiovascular		Administration of hydroxocobalamin/methylcobalamin has been described as beneficial; Due to infectious risks, administration of G-CSF has been described, and early and aggressive treatment of infections may be benefiical; Surveillance for cardiovascular manifestations may allow early management	22922874; 23141461 
ABCG2	74	9429	Blood group, junior system	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	567888; 18522708; 20890084; 22246505; 22246507
ABCG5	13886	64240	Sitosterolemia	AR	Pediatric		Biochemical; Cardiovascular; Hematologic	Biochemical; Cardiovascular		In some individuals, medical (eg, with bile acid resins/lipid-lowering agents) and dietary (eg, with cholesterol and plant fat restriction) treatment may be beneficial for some parameters, and may, along with preventive measures related to cardiovascular manifestations, reduce morbidity and mortality 	11099417; 11138003; 12840092; 16029460; 16472606; 17018391; 17785700; 17976197; 19111681; 20521169; 20543520; 20719861; 21576934; 24166850
ABCG8	13887	64241	Sitosterolemia	AR	Pediatric		Biochemical; Cardiovascular; Hematologic	Biochemical; Cardiovascular		In some individuals, medical (eg, with bile acid resins/lipid-lowering agents) and dietary (eg, with cholesterol and plant fat restriction) treatment may be beneficial for some parameters, and may, along with preventive measures related to cardiovascular manifestations, reduce morbidity and mortality 	11099417; 12840092; 16029460;  15996216
ABHD12	15868	26090	Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract	AR	N/A	N/A	Audiologic/Otolaryngologic; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19005174; 20797687; 22938382 
ABHD5	21396	51099	Chanarin-Dorfman syndrome	AR	N/A	N/A	Biochemical; Dermatologic	General	Manifestations can include severe hepatic sequelae	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10712205; 11590543; 21757733; 22245374; 22373837 
ABO	79	28	Blood group, ABO system	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	4014172; 2647864; 2333095; 1303212; 1572640; 8075282; 7772867; 9099833; 11520811; 12014997; 12829588; 17959777 
ACAD8	87	27034	Isobutyryl-CoA dehydrogenase deficiency	AR	Pediatric		Biochemical; Cardiovascular; Hematologic; Musculoskeletal; Neurologic	Biochemical		Metabolic precautions may be beneficial to prevent and treat acute decompensation; Medical treatment (eg, with oral L-carnitine) has been reported as allowing growth catch-up and normalization of cardiac status	9889013; 12359132; 17304052; 16857760; 17924841; 21290185; 22241096 
ACAD9	21497	28976	Acyl-CoA dehydrogenase family, member 9, deficiency of	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	Biochemical		Individuals may present early in life with findings including neurologic abnormalities, cardiomyopathy, and lactic acidosis, and early institution of medical treatment (eg, with riboflavin) has been reported as leading to marked decreases in morbidity/mortality	17564966; 21057504; 20929961 
ACADM	89	34	Acyl-CoA dehydrogenase, medium chain, deficiency of	AR	Pediatric		Biochemical; Musculoskeletal; Neurologic	Biochemical		Dietary treatment (eg, with frequent feedings in infancy, and low-fat diet for toddlers, as well as bedtime administration of uncooked cornstarch to avoid overnight hypoglycemia); In order to avoid/treat catabolism, simple oral (or IV if necessary) carbohydrates can be effective; Fasting should be avoided, as should infant formulas whose primary fat source is medium-chain triglycerides	947635; 6402754; 6857268; 6646897; 3462713; 3944676; 3822638; 2502671; 2393404; 1361190; 8120710; 7603790; 9158144; 11349232; 11524729; 11409868; 15915086; 15832312; 19780764; 20923556; 20434380; 21239873; 20301597; 23574375
ACADS	90	35	Acyl-CoA dehydrogenase, short-chain, deficiency of	AR	Pediatric		Biochemical;Musculoskeletal; Neurologic	Biochemical		Clinical manifestations range from infantile acute acidosis and muscle weakness to chronic adult myopathy, and in the infantile forms, medical/dietary therapy (eg,  IV glucose/carnitine in the initial phase, and low-fat, diet with MCT oil and carnitine and riboflavin, as well as  avoidance of fasting) can be effective	3571488; 3335634; 2808706; 7776094; 9266373; 9499414; 9578969; 9932958; 11134486; 11524729; 18523805; 18054510; 20376488; 20429031; 21325261; 21500142 
ACADSB	91	36	2-methylbutyryl-CoA dehydrogenase deficiency	AR	N/A	N/A	Biochemical	General		The clinical relevance of the condition is unclear, though some have stated that special attention may be necessary in situations involving potential metabolic decompensation	10832746; 12837870; 16317551; 17883863; 17945527; 20547083; 21290185 
ACADVL	92	37	Acyl-CoA dehydrogenase, very long chain, deficiency of	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Renal	Biochemical; Cardiovascular; Musculoskeletal; Renal		There are multiple forms of VLCAD deficiency, and interventions depend on the form (typical medical/dietary therapy includes IV glucose/carnitine in initial phases, as well as low-fat, diet with MCT oil and carnitine, and avoidance of fasting); In the severe, early-onset form, medical treatment of cardiomyopathy may be beneficial; In thechildhood onset form, treatment of hypoketotic hypoglycemia may be beneficial; In the adult-onset, myopathic form, preventive measures related to with irhabdomyolysis, and myoglobinuria after exercise or fasting may be beneficial	4022672; 2059253; 2000272; 1527994; 8422439; 8356011; 8145917; 7668252; 7769092; 7479827; 8739959; 8554073; 9709714; 9877038; 9546340; 9973285; 10077518; 10790204; 11158518; 11524729; 15210884; 17636072; 19327992; 19208414; 19399638; 19452263; 21531094; 21814341; 22847164; 23480858
ACAN	319	176	Spondyloepimetaphyseal dysplasia, aggrecan type; Spondyloepiphyseal dysplasia, Kimberley type; Osteochondritis dissecans, short stature, and early-onset osteoarthritis 	AD/AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14353963; 14216462; 7331787; 3968094; 1978986; 16080123; 18226555; 19110214; 20137779
ACAT1	93	38	3-oxothiolase deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		Individuals typically present with hypoglycemic or hyperglycemic ketoacidosis due to fasting, illnesses, and dietary changes (eg, increased protein), which can result in severe neurologic sequelae or death, and diagnosis can allow dietary and medical management (eg, protein restriction and l-carnitine supplementation) to avoid acute crises and subsequent sequelae	4143539; 4690360; 4812006; 8103405; 8103405; 9700610; 15877211; 17236799; 18511318; 16950638; 20046049; 20157782; 21669895; 23430882; 23920042; 23958592
ACE	2707	1636	Renal tubular dysgenesis; ACE serum levels	AD/AR	N/A	N/A	Renal	General		The clinical applicability of ACE levels is unclear; For Renal tubular dysgenesis, genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2989970; 1976655; 1328889; 1386652; 8131299; 7909524; 8208911; 8314010; 8675669; 7593601; 9120002; 11076943; 11551873; 11956052; 12666117; 15381116; 15531537; 15277638; 16116425
ACHE	108	43	Blood group, Yt system	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	8488842
ACKR1	4035	2532	Blood group, Duffy system	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	6386656; 8248172; 7663520; 7669660; 7705836; 8547665; 9886340; 9746760; 9731074; 10073905; 10570183; 20932074
ACO2	118	50	Infantile cerebellar-retinal degeneration	AR	N/A	N/A	Neurologic; Ophthalmologic 	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22405087
ACOX1	119	51	Peroxisomal acyl-CoA oxidase deficiency	AR	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Craniofacial; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2894756; 8040306; 8279468; 11815777; 17458872; 18536048
ACP5	124	54	Spondyloenchondrodysplasia with immune dysregulation	AR	Pediatric		Allergy/Immunology/Infectious; Endocrine; Musculoskeletal; Neurologic	Allergy/Immunology/Infectious	Clinically recognizable non-immune features may not be recognized early; The condition can affect multiple organ systems for which early knowledge of disease could be beneficial, including infectious and autoimmune sequelae	Individuals may have immune deficiency, and a variety of infections have been reported, including pneunomia, upper respiratory infections, and severe varicella infections, and thus antiinfectious prophylaxis and  early and aggressive treatment of infections may be beneficial; Individuals may also have a variety of autoimmune manifestations, including hypothyroidism, and treatment may be beneficial	12786759; 17497723; 17163538; 18924170; 21217755; 21217752
ACSF3	27288	197322	Combined malonic and methylmalonic aciduria	AR	Pediatric		Biochemical; Neurologic	Biochemical		Although the optimal treatment (as well as the requirement thereof) is currently unclear, low-protein diet may be beneficial, and general management similar to that in methylmalonic acidemia may be beneficial	9700595; 21785126; 21841779
ACSL4	3571	2182	Mental retardation, X-linked 63	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10854107; 11889465; 12525535
ACTA1	129	58	Myopathy, congenital, with fiber-type disproportion 1; Myopathy, nemaline 3; Myopathy, nemaline, with stiffness and hypertonia	AD/AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9185179; 10508519; 11333380; 15520409; 15468086; 16427282; 19553116; 22442437
ACTA2	130	59	Moyamoya disease; Multisystemic smooth muscle dysfunction syndrome; Aortic aneurysm, familial thoracic 6	AD	Pediatric		Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	Cardiovascular		Surveillance for cardiovascular complications (eg, aortic aneurysm), as well as related preventive measures to help control contributory factors may reduce morbidity and mortality by allowing early diagnosis and treatment; There has been a reported increased risk of aortic dissection with minimal aortic dilatation during the pregnancies of affected women	17994018; 19409525; 22051261; 22302747; 24243736
ACTB	132	60	Dystonia, juvenile-onset; Baraitser-Winter syndrome 2	AD	N/A	N/A	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic 	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3351890; 12325076; 16685646; 22366783; 23649928
ACTC1	143	70	Cardiomyopathy, dilated , 1R; Cardiomyopathy, familial hypertrophic 11; Cardiomyopathy, restrictive; Left ventricular noncompaction; Atrial septal defect 5	AD	Pediatric		Cardiovascular	Cardiovascular	Different ACTC1-related disorders have been associated with pediatric or adult-onset disease, but surveillance beginning in the pediatric period may be beneficial	Surveillance (including with electrocardiogram and echocardiogram), preventive measures, and medical management of cardiomyopathies may be helpful to help decrease morbidity and mortality	9563954; 10330430; 10966831; 6267253; 17611253; 18467357; 18506004; 17947298; 20301486; 20301725; 21239446 
ACTG1	144	71	Deafness, autosomal dominant 20; Baraitser-Winter syndrome 2	AD	N/A	N/A	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	General	Baraitser-Winter syndrome 2 condition can include hearing impairment as well as multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5654493; 3351890; 12519370; 14684684; 13680526; 16773128; 19477959; 22366783
ACTG2	145	72	Megacystis-microcolon-intestinal hypoperistalsis syndrome; Visceral myopathy	AD	Pediatric		Gastrointestinal; Genitourinary; Neurologic	Gastrointestinal		Individuals with Visceral myopathy have been described as presenting with findings including chronic intestinal pseudo-obstruction and related abdominal signs and symptoms, and genetic knowledge may help avoid unnecessary surgery (medical management has been described as at least partially effective in some individuals); Individuals with Megacystis-microcolon-intestinal hypoperistalsis syndrome have been reported as requiring TPN and urinary catheterization)	19098683; 24676022; 24777424
ACTN1	163	87	Bleeding disorder, platelet-type, 15	AD	N/A	N/A	Hematologic	General	Individuals have been described with no or mild bleeding tendency, and it is unclear that genetic diagnosis would enable interventions or differences in management	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23434115
ACTN2	164	88	Cardiomyopathy, dilated, 1AA; Cardiomyopathy, hypertrophic	AD	Pediatric		Cardiovascular	Cardiovascular	There is a paucity of functional data demonstrating causation	Preventive measures and medical management of cardiomyopathy may be helpful to help decrease morbidity and mortality	14567970; 20301486; 20022194; 20301725
ACTN4	166	81	Focal segmental glomerulosclerosis 1	AD	N/A	N/A	Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10700177; 15208719; 19142020; 19357256; 19666657
ACVR1	171	90	Fibrodysplasia ossificans progressiva	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8758048; 17077940; 16642017; 17351709; 18830232; 19330033
ACVR2B	174	93	Heterotaxy, visceral, 4, autosomal	AD	N/A	N/A	Cardiovascular; Gastrointestinal; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9916847
ACVRL1	175	94	Hereditary hemorrhagic telangiectasia, type 2	AD	Pediatric		Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Pulmonary	Cardiovascular; Gastrointestinal; Hematologic; Obstetric; Pharmacogenomic; Pulmonary		There are a number of surveillance/preventive/treatment based measures; These include: epistaxis treatment with humidification, lubricants, hormone therapy, anti-fibrinolytic agents, ablation, surgery, etc.; GI bleeding: iron replacement, hormonal or anti-fibrinolytic medication, surgery, etc.; Pulmonary AVM: catheter occlusion, and preventive measures such as antibiotic prophylaxis; symptomatic cerebral AVMs: surgery/embolotherapy, etc;  Severe hepatic AVMs: liver transplantation if medical management fails; Specific pregnancy-related screening may be indicated; Anemia: Iron replacement or transfusion; Avoidance of certain activities and use of anticoagulant and anti-inflammatory agents (including aspirin) in the case of significant bleeding; For PAH, medical therapy (eg, prostanoids, endothelin receptor antagonists, etc.) may be beneficial, but lung transplantation may be indicated	5037289; 3186989; 8640225; 10946360; 9354504; 11170071; 11484689; 14684682; 16470787; 16155196; 6542389; 17786384; 18498373; 18831062; 18312453; 19439755; 20056902; 20301525
ACY1	177	95	Aminoacylase 1 deficiency	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16274666; 16465618; 17562838; 20480396; 24117009
ADA	186	100	Severe combined immunodeficiency due to adenosine deaminase deficiency	AR	Pediatric		Allergy/Immunology/Infectious; Oncologic	Allergy/Immunology/Infectious; Oncologic	Variants may also contribute to Partial ADA deficiency; Gene therapy may be available, though largely on an experimental basis	Enzyme treatment (with PEG-ADA) is beneficial; Antiinfectious prophylaxis and early and aggressive treatment of infections are indicated; BMT has been described in many individuals; Surveillance for certain neoplasms may be beneficial	4117384; 46025; 1089883; 978319; 18618; 980079; 477037; 38963; 7436484; 6863546; 3781559; 3946419; 3007108; 3475710; 3807953; 3260944; 2783588; 2166947; 8227344; 8099155; 8051429; 1974554; 8023852; 8120281; 9108404; 10021471; 12089448; 14499267; 16905365; 19638621; 21725047; 21865538; 22153773; 22348551; 22447032; 22791287; 22805442; 22968453; 23118212; 23895897
ADAM10	188	102	Reticulate acropigmentation of Kitamura	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23666529
ADAM17	195	6868	Inflammatory skin and bowel disease, neonatal 1	AR	Pediatric		Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal	Allergy/Immunology/Infectious; Cardiovascular		Antiinfectious prophylaxis and  early and aggressive treatment of infections may be beneficial; Individuals may also have cardiovascular manifestations, and surveillance may allow beneficial interventions	22010916
ADAM9	216	8754	Cone-rod dystrophy 9	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11581183; 19409519
ADAMTS10	13201	81794	Weill-Marchesani syndrome 1	AR	Pediatric		Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	Cardiovascular; Ophthalmologic		Individuals can have cardiac anomalies, including long QTc, and awareness may allow for preventive/medical management, which may decrease morbidity and mortality; As the condition can include glaucoma, surveillance can allow early interventions that may potentially be beneficial related to preservation of visual status	11941487; 14598350; 15368195; 17663475
ADAMTS13	1366	11093	Thrombotic thrombocytopenic purpura, familial; Schulman-Upshaw syndrome	AR	Pediatric		Hematologic; Neurologic; Renal	Hematologic; Obstetric		Administration of plasma can be beneficial; Specific treatment in pregnancy may be beneficial	14443744; 651994; 7290149; 11530798; 11586351; 12181489; 12576319; 12637323; 19055667
ADAMTS17	17109	170691	Weill-Marchesani-like syndrome	AR	Pediatric		Musculoskeletal; Ophthalmologic	Ophthalmologic; Pharmacogenomic		Individuals may be at risk of glaucoma, and surveillance may allow early management and preventive measures; Agents that may contribute to glaucoma should be avoided	19836009; 20375329; 22486325 
ADAMTS18	17110	170692	Knobloch syndrome 2; Microcornea, myopic chorioretinal atrophy, and telecanthus; Retinal dystrophy, early onset, autosomal recessive	AR	N/A	N/A	Craniofacial; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21862674; 22686506; 23356391; 23818446
ADAMTS2	218	9509	Ehlers-Danlos syndrome, type VII	AR	Pediatric		Craniofacial; Dermatologic; Musculoskeletal; Obstetric	Obstetric		Individuals may  be prone to injuries (especially during delivery, as multiple congenital skull fractures and intracranial hemorrhage have been reported), and knowledge may allow delivery-based interventions to decrease related morbidity and mortality	1303238; 8215497; 7735500; 10417273; 15373769; 15389701; 18973246
ADAMTSL2	14631	9719	Geleophysic dysplasia 1	AR	Pediatric		Biochemical; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal 	Cardiovascular		The disorder may frequently be clinically recognizable, but individuals can have cardiovascular manifestations such as progressive cardiac valve thickening necessitating surgical interventions very early in childhood, and early diagnosis may be beneficial to allow early treatment	18677313; 21415077; 21683322; 20301776
ADAMTSL4	19706	54507	Ectopia lentis, isolated, autosomal recessive	AR	Pediatric		Ophthalmologic	Ophthalmologic; Pharmacogenomic		Although management related to some manifestations may be made through clinical observations (eg, related to amblyopia), surveillance related to intraocular pressure monitoring may be beneficial to allow prompt interventions; preventive measures (eg, related to contact sports) may be beneficial; Agents that may contribute to glaucoma should be avoided	2377351; 19200529; 20702823; 21051722; 22736615; 2338190
ADAR	225	103	Dyschromatosis symmetrica hereditaria; Aicardi-Goutieres syndrome 6	AD/AR	N/A	N/A	Dermatologic; Hematologic; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12916015; 12713580; 23001123; 24262145; 25243380
ADCK3	16812	56997	Coenzyme Q10 deficiency; Progressive cerebellar ataxia and atrophy; Spinocerebellar ataxia 9	AR	Pediatric		Biochemical; Neurologic	Biochemical		Treatment with coenzyme Q10 may have some benefit in some individuals, though some features may not be affected, and some invidiuals may not derive benefit	12682339; 15326254; 18319074; 18319072; 20580948; 22036850; 22231380 
ADCK4	19041	79934	Nephrotic syndrome, type 9	AR	Pediatric		Renal	Biochemical		The condition manifests as steroid-resistant nephrotic syndrome, with focal segmental glomerulosclerosis, and treatment with coenzyme Q10 has been described as beneficial	24270420
ADCY1	232	107	Deafness, autosomal dominant 44	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	15583425; 24482543
ADCY5	236	111	Dyskinesia, familial, with facial myokymia	AD	Adult		Cardiovascular; Neurologic	Cardiovascular		In addition to neurologic manifestations, individuals have been described with dilated cardiomyopathy and congestive heart failure, and awareness may allow surveillance (eg, with echocardiography), and early management	11310626; 22782511; 24700542
ADK	257	132	Hypermethioninemia due to adenosine kinase deficiency	AD	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Gastrointestinal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21963049
ADNP	15766	23394	Mental retardation, autosomal dominant 28	AD	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24531329
ADRA2C	283	152	Beta-blocker response, association with	AD	Pediatric		General	Pharmacogenomic		The presence of variants may influence medication choice (eg, in congestive heart failure)	17496726
ADRB1	285	153	Beta-blocker response, association with	AD	Pediatric		General	Pharmacogenomic		The presence of variants may influence medication choice (eg, in congestive heart failure)	10212248; 12197595; 12374873; 16844790; 17496726
ADRB2	286	154	Beta-2-adrenoreceptor agonist, reduced response to	AD	Pediatric		General	Pharmacogenomic		Selection of medications (eg, in asthma treatment) may be influenced by the presence of certain variants	8383511; 7706471; 9399966; 11306963; 11739457; 12030897; 12571262; 15284533; 15500895; 15867853; 16596417
ADSL	291	158	Adenylosuccinase deficiency	AR	N/A	N/A	Biochemical; Neurologic	General	As with many disorders involving seizures, appropriate interventions may be beneficial (eg, ketogenic diet has been reported as beneficial)	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6150139; 3234432; 1405483; 1302001; 9266401; 9266351; 10090474; 10888601; 11042421; 12070256; 12833398; 17188615; 18524658; 18649008; 18830228; 20177786; 20933180; 22883297; 23055421; 23504561
AFF2	3776	2334	Premature ovarian failure	XL	Pediatric	Allelic with Mental retardation, X-linked, FRAXE type (XL)	Endocrine; Neurologic; Obstetric	Obstetric	Deletions involving the gene have been described in affected individuals	Genetic knowledge might be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency	8334699; 8023854; 7536393; 7783162; 8673085; 8651274; 9341861; 9475603; 10528856; 12605436; 19136466; 21739600
AFG3L2	315	10939	Spinocerebellar ataxia 28; Ataxia, spastic, 5, autosomal recessive	AD/AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16251216; 20725928; 20208537
AFP	317	174	AFP deficiency, congenital; Hereditary persistence of AFP	AD/AR	N/A	N/A	General	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1690155; 1379776; 7684942; 15280901; 18854864
AGA	318	175	Aspartylglucosaminuria	AR	N/A	N/A	Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; BMT has been described, but did not appear to be overall beneficial	4173687; 5512217; 6796777; 6883788; 3228136; 1904874; 1722323; 1703489; 1765378; 1756604; 1301945; 8405810; 8064811; 9427148; 9627765; 10353787; 11174635; 11796409; 12022293; 12366426; 15127757; 16218917; 23271757
AGBL1	26504	123624	Corneal dystrophy, Fuchs endothelial, 8	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; BMT has been described, but did not appear to be overall beneficial	24094747
AGK	21869	55750	Sengers syndrome	AR	Pediatric	Allelic with Cataract 38 (AR)	Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	Biochemical; Cardiovascular		Individuals can have cardiomyopathy, and early diagnosis may benefit medical management; Avoidance of factors that may precipitate lactic acidosis may be beneficial	1168700; 3789054; 3560758; 3337009; 15168109; 16736096; 22415731; 22277967; 22284826; 23266196 
AGL	321	178	Glycogen storage disease III	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	Biochemical; Pharmacogenomic		Dietary measures (eg, high-protein diet with frequent feeding, including cornstarch) to maintain glucose levels is beneficial; Certain medications should be avoided or used with caution; Experimental treatment (eg, with synthetic ketone bodies) has been described as additionally beneficial; Liver transplantation has been described	5235982; 5285455; 288318; 6572629; 2792130; 2295969; 1293383; 1632441; 8253364; 8273986; 8755644; 8990006; 10472540; 10982190; 10655153; 11977176; 17047887; 18541889; 18924225; 19834502; 21073127; 21857385; 22138524; 22089644; 23207808; 23430490; 23649758; 23688858
AGPAT2	325	10555	Lipodystrophy, congenital generalized, type 1	AR	Pediatric		Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal	Cardiovascular; Endocrine; Gastrointestinal		Dietary measures (eg, restriction of fat intake to 20-30% of total dietary energy) and medications (eg, leptin, though availability may be limited)  may be beneficial; Surveillance for manifestations, including diabetes and cardiac and hepatic manifestations, may allow early diagnosis and treatment	8783769; 11967537; 14602785; 14557463; 15181077; 17671040; 17118991; 19278620; 20301391 
AGPS	327	8540	Rhizomelic chondrodysplasia punctata, type 3	AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7807941; 9553082; 21990100
AGRN	329	375790	Myasthenia, limb-girdle, familial	AR	Pediatric		Musculoskeletal; Neurologic	Musculoskeletal; Neurologic; Pharmacogenomic		Ephedrine treatment has been reported as effective in affected inviduals; Medical treatment with acetylcholine esterase inhibitors and/or potassium channel blocker 3,4-diaminopyridine may be beneficial in many individuals; In infancy, the use of apnea monitors may be indicated; Agents that affect neuromuscular transmission and exacerbate myasthenic manifestations should be avoided 	19631309;  20301347; 22205389; 22678886
AGT	333	183	Renal tubular dysgenesis	AR	N/A	N/A	Renal	Renal		Treatment with fresh frozen plasma in the neonatal period has been reported as effective in terms of maintaing blood pressure and allowing survival	1394429; 8348146; 8513325; 8132767; 7649545; 9120024; 9120002; 9259580; 9421481; 10585456; 11829142; 11731937; 15023884; 16116425; 17047091; 17036344; 20978123; 22685354 
AGTR1	336	185	Renal tubular dysgenesis	AR	N/A	N/A	Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8021009; 16116425; 17668390
AGTR2	338	186	Mental retardation, X-linked 88	XL	N/A	N/A	Neurologic	General	The evidence of mutations as being related to disease causation has been questioned due to subsequent population-based studies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12089445; 12746399; 14598163; 14722754; 16463274; 22269148; 23871722
AGXT	341	189	Hyperoxaluria, primary, type 1	AR	Pediatric		Biochemical; Cardiovascular; Renal	Biochemical; Cardiovascular; Renal		Fluid intake and medical management (eg, pyridoxine in those who are pyridoxine responsive, potassium/sodium citrate or neutral orthophosphate) can be beneficial to reduce calcium oxalate supersaturation/biosynthesis and reduce stone formation; Organ transplantation (preemptive liver transplantation or liver/kidney transplantation) may be beneficial; Surveillance for renal and related complications (which can include cardiac dysrhythmias) can be beneficial; Dehydration and excessive intake of oxalate-rich foods should be avoided, as well as certain vitamins and medications	449695; 6472428; 3974685; 2887776; 2797068; 2189732; 7969325;  1703535; 2039493; 1961759; 9604813; 10586179; 10453743; 10485304; 11562405; 8507692; 11688375; 12543880; 15327387; 16247357; 15855742; 15464418; 15840016; 15849466; 15767715; 16810517; 16916735; 17460142; 17495019; 18359396; 18282470; 18337715; 19935811; 19571789; 19225556; 19132372; 19479957; 20733487; 20016466; 20301460; 20490484; 22547750; 22821680; 22956877; 23439734; 23810941; 24012869
AHCY	343	191	Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Neurologic	Biochemical		Dietary restriction (eg, of methionine) and supplementation (eg, of phosphatidylcholine) may be beneficial in some individuals	2380820; 15024124; 20852937; 21732553 
AHDC1	25230	27245	Mental retardation, autosomal dominant 25 (Xia-Gibbs syndrome)	AD	N/A	N/A	Audiologic/Otolaryngologic; Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24791903
AHI1	21575	54806	Joubert syndrome 3	AR	N/A	N/A	Neurologic; Ophthalmologic; Renal	General	The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial	The condition may involve multi-systemic manifestations, including sequelae affecting the renal system, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial	15467982; 15322546; 16155189; 16453322; 20081859; 21937992
AICDA	13203	57379	Immunodeficiency with hyper-IgM, type 2	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals have elevated serum IgM levels and absent IgG, IgA, and IgE, and are thus highly susceptible to severe bacterial infections (eg, bacterial respiratory and GI infections), such that antiinfectious prophylaxis (including with IVIG, which has been reported to be effective) and early and aggressive treatment of infections may be beneficial; Individuals may also have autoimmune and inflammatory manifestions, some of which may benefit from early knowledge and interventions, including hemolytic anemia and immune thrombocytopenia	11007475; 14962793; 15358621; 19575287; 21192628 
AIFM1	8768	9131	Combined oxidative phosphorylation deficiency 6; Cowchock syndrome	XL	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20362274; 22019070; 23217327 
AIMP1	10648	9255	Leukodystrophy, hypomyelinating, 3	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21092922; 21397066; 21397067 
AIP	358	9049	Pituitary adenoma, familial isolated	AD	Pediatric		Endocrine; Oncologic	Endocrine; Oncologic	Multiple tumor types have been described	Surveillance and/or awareness of cancer risk  may allow early diagnosis of pituitary tumors (as well as related manifestations, such as hypertension, hypogonadism, diabetes mellitus, and osteoporosis), which could potentially be beneficial to allow early medical (eg, with somatostatin analogs, growth hormone receptor antagonists, dopamine agonists) or surgical treatment; Surveillance post-treatment may also be beneficial to detect recurrence/new adenomas	7621566; 11158006; 16728643; 17299063; 22319033; 17609395; 17244780; 17360484; 17341560; 18381572; 20570174; 20685857; 19945022; 20506337; 20507346; 21591954; 21753072; 22319033; 22720333; 22612670; 23270713; 23321498; 23674160; 23743763; 24078436
AIPL1	359	23746	Leber congenital amaurosis 4; Retinitis pigmentosa, juvenile, AIPL1-related; Cone-rod dystrophy, AIPL1-related	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10711674; 10615133; 10873396; 21602930; 21900377; 21474771; 22412862
AIRE	360	326	Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia	AD/AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic	Allergy/Immunology/Infectious; Endocrine		Individuals need life-long follow-up, as sequelae may appear later in life; Endocrine findings can include adrenocortical failure and severe hypocalcemia; Infectious complications, such as candiasis, and septicemia, are frequent, and prompt and aggressive treatment of infections may be beneficial	7024719; 3496374; 2348835; 1453436; 9398840; 9398839; 9543115; 9837820; 9717837; 11018166; 11600535; 14557425; 16965330; 17539912; 19758376; 19807739
AK1	361	203	Adenylate kinase deficiency, hemolytic anemia due to	AR	Pediatric		Hematologic; Neurologic 	Hematologic		Individuals present with hemolytic anemia (as well as neurodevelopmental features, at least in some reported individuals), and splenectomy has reported as being effective in treatment of hemolysis	179026; 5546784; 6308059; 2542324; 7947281; 9432020; 17662886 
AK2	362	204	Reticular dysgenesis 	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic		Individuals typically die in early infancy due to severe infections; Early diagnosis allowing HSCT can be effective	13840590; 6132037; 19043416; 19043417
AKAP9	379	10142	Long QT syndrome 11	AD	Pediatric		Cardiovascular	Cardiovascular		In order to prevent sequelae including syncope, cardiac arrest and sudden death prophylactic use of beta blockers in asymptomatic individuals may be beneficial; ICD may be indicated for individuals refractory to beta-blocker treatment or  with history of cardiac arrest; Agents that can contribute to prolonged QT or related dysrhythmias should be avoided, as should activities associated with high stress/intense exertion	10220144; 18093912; 20809527; 21430528; 20301308 
AKR1C2	385	1646	46,XY sex reversal 8	AR	Pediatric		Endocrine; Genitourinary; Oncologic	Genitourinary; Oncologic		Surveillance and/or awareness of cancer risk, and preventive measures may be beneficial to reduce the risk of gonadal tumors	4352099; 21802064
AKR1D1	388	6718	Bile acid synthesis defect, congenital, 2	AR	Pediatric		Gastrointestinal	Gastrointestinal		Early interventions, such as bile replacement therapy, can be beneficial, though liver transplant may be necessary in severe cases 	2897546; 3198770; 2072042; 2248502; 8707100; 12970144; 15030995; 20522910; 23160874
AKT1	391	207	Cowden syndrome 6; Proteus syndrome 	AD	Pediatric		Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Neurologic; Oncologic; Pulmonary	Cardiovascular; Hematologic; Oncologic; Pulmonary	 In Proteus syndrome, mutations may be found on peripheral blood testing, but affected tissue must typically be tested for molecular diagnosis	In Cowden syndrome 5 , individuals have been described with manifestations including breast, renal, and thyroid cancer, and surveillance may allow early detection and management of neoplasms; In Proteus syndrome, individuals may be at risk for a variety of manifestations, some of which may be occult; Surveillance for hematologic/vascular manifestations (eg, deep vein thrombosis and pulmonary embolism) can allow early detection and treatment; Surveillance for pulmonary disease (as patients are at risk for restrictive lung disease) can allow early detection and treatment; As individuals may be at increased risk for neoplastic processes, routine monitoring by history and physical examination (without separate imaging) may allow early detection of neoplasms 	21793738; 22876373; 23246288 
AKT2	392	208	Hypoinsulinemic hypoglycemia with hemihypertrophy	AD	Pediatric		Endocrine; Musculoskeletal	Endocrine		Individuals may present early in life with severe hypoglycemia (and related sequelae, including seizures and death), and in order to prevent severe hypoglycemia, specific feeding regimens (eg, overnight enteral carbohydrate feeding) may be beneficial	15166380; 14764948; 19164855; 21979934
AKT3	393	10000	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2	AD	N/A	N/A	Dermatologic; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22729224; 22729223; 23745724
ALAD	395	210	Porphyria, acute hepatic	AR	Pediatric		Biochemical; Gastrointestinal; Neurologic	Biochemical; Pharmacogenomic	Digenic inheritance (with CPOX) has been described	Medical treatment (eg, with agents such as infusion of heme arginate) can be effective; Affected individuals are endangered by certain agents, including alcohol ingestion or lead exposure 	513604; 3559484; 2600550; 2063868; 7490911; 9732973; 1905639; 1716854; 1569184; 9516683; 11071662; 10706561; 11342419; 15303011; 16343966; 16398658; 17236137; 17366816
ALAS2	397	212	Anemia, sideroblastic, X-linked; Protoporphyria, erythropoietic	XL	Pediatric		Dermatologic; Gastrointestinal; Hematologic	Dermatologic; Gastrointestinal; Hematologic		In X-linked sideroblastic anemia, phlebotomy  can be effective to prevent the development of complications such as cardiovascular and liver damage, as well as diabetes, and is typically most effective in individuals who are pyridoxine-responsive; In Erythropoietic protoporphyria, sunlight protection (and possibly beta-carotene and alpha-melanocyte treatments) may be beneficial, as well as medical treatment of hepatic manifestations (eg, with cholestyramine, plasmapharesis and IV hemin), though liver transplantations may be necessary, while BMT has been reported as effective	14247476; 130377; 1570328; 7949148; 7560104; 10029606; 10886220; 12531813; 16315313; 16735131; 18760763; 19144952; 19656325; 21252495; 23016163; 23263862
ALB	399	213	Dysalbuminemic hyperthyroxinemia; Analbuminemia	AD/AR	Pediatric	Allelic with Bisalbuminemia (AD); Paralbuminemia (AD); Dysalbuminemic hyperzincemia (AD)	Endocrine; Musculoskeletal; Renal	Endocrine; Pharmacogenomic; Renal	Depending on the disorder, manifestations may primarily affect the endocrine system (as in Dysalbuminemic hyperthyroxinemia) or may result in findings such as edema and hypercholesterolemia, as well as pharmacogenomic implications (as in Analbuminemia)	In Dysalbuminemic hyperthyroxinemia, genetic diagnosis may help avoid unecessary treatment; In Analbuminemia, medical treatment of sequelae of low albumin (eg, dysplipidemia) can be beneficial, and precautions with certain medications may be indicated	13673098; 13785411; 14187073; 5926635; 1269174; 2430733; 3578276; 3407659; 3353369; 2762316; 2404284; 2104980;  6310605; 7829599; 8048949; 8064810; 8621984; 9329347; 9589637; 10842774; 10946882; 11781148; 12099390; 12743361; 15541334; 15300429; 16183048; 15996651; 18459107; 20638375; 20415703; 22327004; 22227324
ALDH18A1	9722	5832	Cutis laxa, autosomal recessive, type IIIA	AR	N/A	N/A	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11092761; 18478038; 21739576; 24913064
ALDH1A3	409	220	Microphthalmia, isolated 8	AR	N/A	N/A	Neurologic; Ophthalmologic	General	An individual with cardiovascular anomalies has been described, but it is unclear if this is part of the syndrome	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23312594
ALDH3A2	403	224	Sjogren-Larsson syndrome	AR	N/A	N/A	Biochemical; Dermatologic; Neurologic; Ophthalmologic	General	Medical treatment (eg, with Zileuton) may be beneficial for certain aspects	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13354244; 13457946; 8176565; 9027499; 9829906; 11124298; 11408337; 16476818; 21684788; 21872273; 22397046; 22426667; 22833178; 23034980
ALDH4A1	406	8659	Hyperprolinemia, type II 	AR	N/A	N/A	Biochemical; Neurologic	General	The clinical relevance of the condition is unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9700195; 10780262
ALDH5A1	408	7915	Succinic semialdehyde dehydrogenase deficiency	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7226548; 6627675; 9266358; 9093300; 9683595; 12743223; 14635103; 15059623; 17438226; 20304328; 21612881; 22437753 
ALDH6A1	7179	4329	Methylmalonate semialdehyde dehydrogenase deficiency	AR	N/A	N/A	Biochemical	General	The clinical relevance of the condition is unclear, though some individuals with developmental delay have been reported	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3939535; 3117077; 9787093; 10947204; 21863277
ALDH7A1	877	501	Epilepsy, pyridoxine-dependent	AR	Pediatric		Neurologic	Neurologic		Individuals frequently present in the neonatal period with seizures (neonatal lactic acidosis and hypoglycemia have also been described), and the seizures, though otherwise refractory to other anti-epileptics, can typically be controlled via medical management (daily pyridoxine monotherapy), though the condition may still impact longer-term developmental manifestations	13133562; 14131641; 3977296; 16159904; 16075246; 16491085; 17068770; 17721876; 21704546; 20301659; 22529283; 22728861; 22804844; 23054014 
ALDOA	414	226	Glycogen storage disease XII	AR	Pediatric		Biochemical; Hematologic; Musculoskeletal; Neurologic; Renal	Biochemical; Hematologic; Renal		Individuals can have rhabdomyolysis from stressors such as febrile illness, and appropriate precautions and management may be beneficial; Aldolase A deficiency is also asociated with hereditary hemolytic anemia, and transfusions and splenectomy have been described in treatment	4788792; 7331996; 3688035; 2825199; 8598869; 14615364 
ALDOB	417	229	Fructose intolerance, hereditary	AR	Pediatric		Biochemical; Gastrointestinal; Neurologic; Renal	Biochemical; Gastrointestinal		Clinical manifestations, which can be severe/fatal, occur with the dietary introduction of fructose or sucrose, and dietary measures (fructose restriction) can be effective	13358219; 14060577; 13942402; 13959929; 4166890; 5637008; 4212946; 213970; 491970; 6888454; 3383242; 2916618; 2349937; 1967768 ; 2314976; 2122082; 8535439; 9610797; 18541450; 20848650; 20882353; 22375183 
ALG1	18294	56052	Congenital disorder of glycosylation, type Ik	AR	Pediatric	 	Biochemical; Gastrointestinal; Hematologic; Neurologic; Renal	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	14709599; 14973782; 14973778; 20679665; 22966035
ALG11	32456	440138	Congenital disorder of glycosylation, type Ip	AR	Pediatric	 	Biochemical;  Hematologic; Neurologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	20080937; 22213132
ALG12	19358	79087	Congenital disorder of glycosylation, type Ig	AR	Pediatric	 	Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Craniofacial; Genitourinary; Hematologic; Musculoskeletal; Neurologic	Allergy/Immunology/Infectious; Hematologic	Hepatic-metabolized agents should be avoided	As the condition can include immunodeficiency and frequent infections, prophylaxis and early and aggressive treatment of infections may be beneficial; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	11983712; 12217961; 17506107
ALG13	30881	79868	Congenital disorder of glycosylation, type Is	XL	Pediatric	 	Allergy/Immunology/Infectious; Biochemical; Hematologic; Neurologic; 	Allergy/Immunology/Infectious; Hematologic	Hepatic-metabolized agents should be avoided	As the condition can include immunodeficiency and frequent infections, prophylaxis and early and aggressive treatment of infections may be beneficial; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	22492991
ALG14	28287	199857	Congenital myasthenic syndrome, autosomal recessive	AR	Pediatric		Musculoskeletal	Musculoskeletal		Individuals have been described as manifesting with progressive weakness, and have been reported who have demonstrated long-term benefit from medical treatment (with anticholinesterase medication)	23404334
ALG2	23159	85365	Congenital disorder of glycosylation, type Ii; Congenital myasthenic syndrome, autosomal recessive	AR	Pediatric		Biochemical; Hematologic; Neurologic; Ophthalmologic	Hematologic; Neurologic	Hepatic-metabolized agents should be avoided	In  Congenital disorder of glycosylation, type Ii, awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery; In Congenital myasthenic syndrome, autosomal recessive, individuals have been described as manifesting with progressive weakness, and have been reported who have benefited from medical treatment (with anticholinesterase medication)	12684507; 23404334
ALG3	23056	10195	Congenital disorder of glycosylation, type Id	AR	Pediatric	 	Biochemical;  Hematologic; Neurologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	8552211; 10581255; 15108280; 15840742; 17551933; 18679822 
ALG6	23157	29929	Congenital disorder of glycosylation, type Ic	AR	Pediatric	 	Biochemical; Endocrine; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	10359825; 10914684; 10924277; 16007612; 21334936
ALG8	23161	79053	Congenital disorder of glycosylation, type Ih	AR	Pediatric	 	Biochemical; Cardiovascular; Gastrointestinal;  Hematologic; Neurologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	12480927; 15235028; 19648040; 19688606; 22306853 
ALG9	15672	79796	Congenital disorder of glycosylation, type Il	AR	Pediatric	Pediatric	Biochemical; Cardiovascular; Gastrointestinal;  Hematologic; Neurologic; Renal	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	15148656; 15945070; 19451548 
ALK	427	238	Neuroblastoma, susceptibility to, 3	AD	Pediatric		Oncologic	Oncologic		Surveillance (eg, with frequent abdominal ultrasound and urinary catecholamine testing) and awareness of cancer risk may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality	18923523; 18724359; 18242317; 20301782 
ALMS1	428	7840	Alstrom syndrome	AR	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Gastrointestinal; Ophthalmologic; Renal	Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Gastrointestinal; Renal		The condition may be recognizable from early manifestations (eg, related to visual loss), but dilated or restricted cardiomyopathy is common, and measures to decrease related morbidity and mortality may be beneficial; Management related to other sequelae, such as endocrine (eg, diabetes mellitus), renal, and hepatic manifestations, may also be beneficial; Recognition of hearing impairment can allow interventions related to speech and language development	13649370; 5824738; 3766665; 3687707; 2231654; 1746604; 8418611; 8488920; 8636816; 9066877; 9409865; 9663233; 11343329; 11941369; 11941370; 17594715; 17850632; 22043170; 21522186; 20301444 
ALOX12B	430	242	Ichthyosiform erythroderma, congenital, nonbullous, 1	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11773004; 16116617; 20301593
ALOX5	435	240	Asthma, diminished response to antileukotriene treatment in	AD	Pediatric		General	Pharmacogenomic		Variants may have pharmacogenomic importance	9062372; 9698605; 10369259; 14702425
ALOXE3	13743	59344	Ichthyosiform erythroderma, congenital, nonbullous, 1	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11773004; 16116617; 19131948; 20301593
ALPL	438	249	Hypophosphatasia; Odontohypophosphatasia	AD/AR	Pediatric		Dental; Endocrine; Musculoskeletal; Neurologic	Endocrine; Neurologic		In some forms, abnormal calcium levels can be treated; Seizures can be treated with vitamin B6; Bisphosphonates and excess vitamin D should be avoided due to potential hypercalcemia leading to renal damage; Enzymatic therapy has shown benefit in individuals with severe forms of hypophosphatasia	18110134 ; 13800162; 4288761; 4309618 ; 5013867; 7235780; 7305584; 7072744; 7182980; 3960066; 1409720; 3174660; 8406453; 10332035; 10872988; 11479741; 11999978; 12357339; 17519318; 17213282; 21488855; 20978533; 20301329; 22397652 
ALS2	443	57679	Spastic paralysis, infantile onset ascending; Primary lateral sclerosis, juvenile; Amyotrophic lateral sclerosis, juvenile	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2328408; 7920663; 8745388; 11586298; 11586297; 12145748; 12509863; 16718699; 18523452; 18810511; 19122027
ALS2CL	20605	259173	Schizophrenia	AD	N/A	N/A	Neurologic	General		Evidence or clinical applicability  is unclear	21743468; 23425335
ALX1	1494	8092	Frontonasal dysplasia 3	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20451171
ALX3	449	257	Frontonasal dysplasia 1	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17963218; 19409524; 22106187 
ALX4	450	60529	Parietal foramina 2; Frontonasal dysplasia 2	AD/AR	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General	Variants may contribute to nonsyndromic craniosynostosis	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11106354; 11137991; 16319823; 19692347; 20301307; 22140057; 22829454; 23401352; 24764194
AMACR	451	23600	Bile acid synthesis defect, congenital, 4; Alpha-methylacyl-CoA racemase deficiency	AR	Pediatric		Biochemical; Endocrine; Gastrointestinal; Neurologic; Ophthalmologic	Biochemical; Gastrointestinal		Individuals with Bile acid synthesis defect, congenital, 4 may present with manifestations of hepatic disease, and medical therapy (eg, with oral cholic acid, and Vitamin K for bleeding) has been reported as beneficial; In Alpha-methylacyl-CoA Racemase deficiency, early diagnosis may allow potentially benefical dietary/medical therapy (eg, restriction of dietary phytanic acid and pristanic acid)	9584266; 10655068; 11473573; 12512044; 15249642; 18032455; 20821052; 21576695; 23286897 
AMELX	461	265	Amelogenesis imperfecta,  type 1E	XL	N/A	N/A	Dental	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1916828; 7782077; 15111628
AMER1	26837	139285	Osteopathia striata with cranial sclerosis	XL	N/A	N/A	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19079258; 20209645; 20950377; 22987541  
AMH	464	268	Persistent Mullerian duct syndrome, type I	AR	Pediatric		Endocrine; Genitourinary; Oncologic	Endocrine; Oncologic; Genitourinary		In males, recognition can allow surveillance and surgical explorations to correct manifestations such as cryptorchdisim, which can be important to preserve fertility and decrease the chance of related sequelae (eg, testicular tumors)	8872466; 8895659; 11760020; 15878900; 18547961; 22188863 
AMHR2	465	269	Persistent Mullerian duct syndrome, type II	AR	Pediatric		Endocrine; Genitourinary; Oncologic	Endocrine; Oncologic; Genitourinary		In males, recognition can allow surveillance and surgical explorations to correct manifestations such as cryptorchdisim, which can be important to preserve fertility and decrease the chance of related sequelae (eg, testicular tumors)	8162013; 7493017; 8872466; 8895659; 15878900; 19457927 
AMN	14604	81693	Megaloblastic anemia-1, Norwegian type	AR	Pediatric		Gastrointestinal; Hematologic; Renal	Gastrointestinal		Early diagnosis is beneficial, as  early detection may allow life-long medical treatment with parenteral hydroxocobalamin, which can ameliorate morbidity and mortality 	12590260; 17114957; 17285242; 18181028; 22078000; 22854512; 22631584
AMPD1	468	270	Myoadenylate deaminase deficiency	AR	N/A	N/A	Biochemical; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1631143; 10086964; 10996775; 11102975; 11331279; 22538307 
AMPD2	469	271	Pontocerebellar hypoplasia type 9; Spastic paraplegia 63	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23911318; 24482476
AMPD3	470	272	Erythrocytic AMP deaminase deficiency	AD/AR	N/A	N/A	General	General		The condition may not be clinically relevant	3804327; 7881427; 8004104
AMT	473	275	Glycine encephalopathy	AR	Pediatric		Biochemical; Neurologic; Ophthalmologic	Biochemical; Pharmacogenomic		There is no current effective treatment for severe disease; however, children with mutations associated with residual GCS enzyme activity treated aggressively early with sodium benzoate and N-methyl D-aspartate receptor site antagonists may have improved outcomes; Valproate should be avoided	11139253; 12948742; 16151895; 16450403; 20301531; 19299230; 21470805 
ANG	483	283	Amyotrophic lateral sclerosis 9	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15557516; 16501576; 17886298; 18087731; 18852347; 19153377; 20577002
ANGPTL3	491	27329	Hypobetalipoproteinemia, familial, 2	AR	N/A	N/A	Gastrointestinal	General	Unlike hypobetalipoproteinemia due to mutations in APOB, individuals with mutations in ANGPTL3 do not appear to to have increased susceptibility to hepatic steatosis or gastrointestinal or cardiovascular manifestations compared to unaffected relatives; Heterozygous individuals may demonstrate laboratory-based manifestations (eg, lower plasma LDL and triglycerides)	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9508071; 9508071; 20942659; 22659251
ANK1	492	286	Spherocytosis, hereditary 1	AD/AR	Pediatric		Hematologic	Hematologic		Some individuals may have therapy requiring neonatal hyperbilirubinemia, as well as severe, transfusion-requiring anemia	14467968; 4476391; 2675425; 1832935; 1486040; 8640229; 9887280; 430667; 17327413; 20512576 
ANK2	493	287	Long QT syndrome, 4; Cardiac arrhythmia, ankyrin-B-related 	AD	Pediatric		Cardiovascular	Cardiovascular		Individuals may present with a variety of manifestations depending on the type of arrhythmia, including stress/exercise-induced arrhythmias, syncope, and sudden cardiac death, and surveillance (eg, with electrocardiogram) and medical (eg, including ICD placement) management may be effective to prevent severe sequelae of cardiac arrhythmias	7485162; 12571597; 15178757; 17242276; 17940615; 18790697; 18832177; 20809527; 21859974 
ANKH	15492	56172	Craniometaphyseal dysplasia; Chondrocalcinosis 2 	AD	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8528213; 9915952; 11326272; 11326338; 12297987; 12297989; 20301634; 20358596; 22150416; 22647861 
ANKRD11	21316	29123	KBG syndrome	AD	N/A	N/A	Craniofacial; Dental; Musculoskeletal; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15523620; 15378538; 21782149; 22307766 
ANKRD26	29186	22852	Thrombocytopenia 2	AD	Pediatric		Hematologic	Hematologic	A variant in ABCD5 was reported as causative	Individuals may have bleeding tendency, and precautions (eg, in surgical situations) may be beneficial	10541317; 10521306; 10891439; 20626622; 21211618
ANKS6	26724	203286	Nephronophthisis 16	AR	N/A	N/A	Cardiovascular; Gastrointestinal; Renal	General	Renal transplant has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23793029
ANLN	14082	54443	Focal segmental glomerulosclerosis 8	AD	N/A	N/A	Renal	General	Renal transplant has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24676636
ANO10	25519	55129	Spinocerebellar ataxia, autosomal recessive 10	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21092923; 22008874 
ANO3	14004	63982	Craniocervical dystonia, autosomal dominant (Dystonia 24)	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23200863
ANO5	27337	203859	Gnathodiaphyseal dysplasia	AR	Pediatric	Allelic with Miyoshi muscular dystrophy 3 (AR); Muscular dystrophy, limb-girdle, type 2L (AR)	Allergy/Immunology/Infectious; Musculoskeletal	Allergy/Immunology/Infectious		Individuals have been reported as being frequently affected by osteomyelitis of the jaw, and awareness of the risk may allow early detection and management of lesions	5816667; 9673985; 15124103; 17132147; 17008331; 20096397; 20692837; 21186264; 22951575; 21820307; 22402862; 22499103
ANO6	25240	196527	Scott syndrome	AR	Pediatric		Hematologic	Hematologic		Though manifestations tend to be milder than in other bleeding disorders, precautions related to certain circumstances, such as in surgery, may be beneficial	572637; 7989579; 21107324
ANTXR1	21014	84168	Hemangioma, capillary infantile, susceptibility to; Growth retardation, alopecia, pseudoanodontia, and optic atrophy (GAPO syndrome)	AD/AR	N/A	N/A	Craniofacial; Dental; Dermatologic; Musculoskeletal; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9180938; 9298746; 18931684; 19367160; 23602711
ANTXR2	21732	118429	Hyalinosis, infantile systemic; Fibromatosis, juveline hyaline	AR	Pediatric		Allergy/Immunology/Infectious; Dental; Dermatologic; Gastrointestinal; Musculoskeletal	Allergy/Immunology/Infectious; Dermatologic; Musculoskeletal		The condition may be clinically recognizable, but involves manifestations that require clinical care, such as fracture susceptibility, intractable diarrhea, and infection susceptibility, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	20896407; 20896998; 55105; 2434938; 2433666; 3544844; 487969; 11206353; 12214284; 11298373; 12973667; 14508707
AP1S2	560	8905	Mental retardation, X-linked syndromic, Fried type (Pettigrew syndrome)	XL	N/A	N/A	Craniofacial; Neurologic; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5054319; 10398241; 12599187; 17617514; 18428203; 19377476; 2018058; 22210230; 23756445
AP1S3	18971	130340	Psoriasis 15, pustular, susceptibility to	AD	N/A	N/A	Allergy/Immunology/Infectious; Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24791904
AP3B1	566	8546	Hermansky-Pudlak syndrome 2	AR	Pediatric		Allergy/Immunology/Infectious; Dental; Dermatologic; Hematologic; Neurologic; Ophthalmologic; Pulmonary	Allergy/Immunology/Infectious; Dermatologic; Hematologic; Pulmonary		Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination  	10024875; 11809908; 16507770; 16537806; 20301464; 23215637 
AP4B1	572	10717	Spastic paraplegia 47, autosomal recessive	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21620353; 22290197 
AP4E1	573	23431	Spastic paraplegia 51, autosomal recessive	AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21620353; 20972249; 21937992
AP4M1	574	9179	Spastic paraplegia 50, autosomal recessive	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19559397; 21937992
AP4S1	575	11154	Spastic paraplegia 52, autosomal recessive	AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21620353
AP5Z1	22197	9907	Spastic paraplegia 48, autosomal recessive	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20613862; 22554690 
APC	583	324	Familial adenomatous polyposis; Gardner syndrome; Desmoid disease, hereditary	AD	Pediatric		Dental; Dermatologic; Musculoskeletal; Oncologic; Ophthalmologic	Oncologic		Individuals may be at risk for a variety of neoplasms, and surveillance (including for thyroid disease, duodenal and colonic neoplasms, and hepatoblastoma, the latter with ultrasound and serum AFP measurement, as well as for other types of neoplastic manifestations) may allow early detection and management, which may reduce morbidity and mortality; In FAP, medical management (with NSAIDs) have been reported to result in adenoma regression and decreased polyp number; Colectomy is indicated when a specific numeric/pathologic adenomatous burden has been reached 	14902760; 14933371; 13707264; 13891268; 13946545; 14136536; 5644968; 5660317; 5660235; 5443116; 4739325; 4853059; 1111674; 856075; 880737; 739523; 758668; 7446647; 7296952; 7067564; 6121129; 7172944; 6887943; 6129922; 6690356; 2435780; 2827474; 3033343; 3821797; 3800608; 2848134; 2848134; 3338026; 2896968; 3354603; 2156161; 1658283; 1651174; 1651563; 1324223; 1317264; 1329510; 1314729; 1544113; 1316610; 1316858; 8281160; 8276387; 8244107; 8105087; 8385741; 8037405; 8064829; 7661930; 8826936; 8940264; 8940262; 8968744; 9215849; 9585611; 10504375; 10077730; 10782927; 10815155; 10874062; 11932472; 12621137; 17135589; 18395100; 19793053; 20301519; 20400027; 20105204; 22305464; 22773231; 22886683 
APCDD1	15718	147495	Hypotrichosis 1	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10878665; 20393562; 22512811
APOA1	600	335	Hypoalphalipoproteinemia; Amyloidosis, systemic nonneuronopathic	AD/AR	Pediatric		Cardiovascular; Gastrointestinal; Renal	Cardiovascular; Gastrointestinal; Pharmacogenomic	Though manifestations have been described in adults, surveillance and interventions should likely begin in the pediatric period	In Hypoalphaliproteinemia, intervention to decrease risk factors contributing to cardiovascular disease (eg, CAD and stroke), as well as early surveillance and intervention in the case of findings such as CAD, may be beneficial; In Amyloidosis, liver transplantation can correct the underlying metabolic defect	4304452; 7430351; 6776144; 7249374; 7080131; 7078608; 6818131; 6308458; 6131168; 6401735; 6401735; 3118360; 3141894; 2512329; 2512329; 1901417; 1502149; 8240372; 8282791; 7981179; 8675681; 9514407; 9916936; 10487826; 9931341; 12270762; 12050338; 17991432; 21122686; 21443680; 21875686
APOA2	601	336	Apolipoprotein A-II deficiency	AR	N/A	N/A	Cardiovascular 	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2107739; 12522687; 24387992
APOA5	17288	116519	Hyperchylomicronemia	AD/AR	Pediatric		Cardiovascular; Gastrointestinal	Cardiovascular	Variants in additional genes may contribute to phenotypic manifestations	Individuals may have severe hypertriglyceridemia, and interventions related to factors that contribute to cardiovascular sequelae (including through diet and exercise control) may be beneficial, though individuals may develop refractory hypertriglyceridemia	16143024; 16200213; 19410254; 19447388; 21993410; 22239554 
APOB	603	338	Hypobetalipoproteinemia, familial; Hypercholesterolemia, familial	AD/AR	Pediatric		Cardiovascular; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic	Cardiovascular; Gastrointestinal	Variants in multiple related genes (eg, LDLR) may have additive effects	In hypobetalipoproteinemia, dietary measures (eg, with a low fat diet and supplementation of essential fatty acids and fat-soluble vitamins) can be beneficial, and early initiation can prevent/decrease severe sequelae; Some heterozygous variants may be associated with familial hypercholesterolemia, and dietary/lifestyle/medical measures may be beneficial to reduce the risk of sequelae including coronary artery disease	221546; 7229035; 3771801; 3680528; 3473077; 3584472; 2843815; 2903181; 3399894; 2567736; 2574033; 2563166; 3477815; 2614276; 2725600; 2280177; 2164382; 2310429; 2312735; 1939657; 2022744; 1360085; 1562615; 1600334; 1424233; 1466657; 8215738; 8318993; 8318509; 7711417; 8305410; 8004802; 7883971; 8723684; 8792774; 9108789; 9081691; 9603795; 10952765; 11781700; 11494965; 11940084; 12124991;  15984016; 17158591; 18492086; 18354102; 20686565; 21981844; 24288038
APOC2	609	344	Hyperlipoproteinemia, type Ib	AR	Pediatric		Cardiovascular; Gastrointestinal; Neurologic	Cardiovascular; Gastrointestinal		Depending on the severity of disease, individuals may present with manifestations ranging from neonatal encephalopathy to episodic acute pancreatitis, and dietary measures (eg, with low-fat diet, and medium-chain triglyceride supplementation in infancy) can be beneficial to help control lipid abnormalities, including decreasing the risk of episodes of acute pancreatitis; Treatment of acute pancreatitis involves fasting with low-calorie infusion, but serum triglycerides can also be rapidly decreased in emergent situations through normal plasma transfusion; Medical treatment (eg, with fibrates) may be beneficial in adults	565877; 213719; 227429; 6101731; 6475985; 3944267; 3467353; 3171393; 3225819; 1479292; 2477392; 2501098; 7815420; 10225669; 12049186; 12783430; 16153625; 22129523 
APOC3	610	345	Hyperalophalipoproteinemia 2	AD	N/A	N/A	Cardiovascular 	General		The clinical applicability of Hyperalophalipoproteinemia 2 is unclear, though variants may be related to lower triglyceride levels and protection against cardiovascular disease	2914370; 2022742; 16813599; 19074352;  24941081; 24941082; 25225788
APOE	613	348	Dysbetalipoproteinemia, familial (Hyperlipoproteinemia, type III); Lipoprotein glomerulopathy; Sea-blue histiocyte disease	AD/AR	Pediatric		Cardiovascular; Gastrointestinal; Hematologic; Renal	Cardiovascular; Gastrointestinal; Renal		In familial dysbetalipoproteinemia, dietary and medical measures related to treating abnormal lipid profiles (including apharesis in some individuals) can be beneficial, including as relates to the risk of cardiovascular disease; In LPG, early diagnosis may be advantageous in order to allow medical treatment (eg, with fibrate therapy); In Sea-blue histiocyte disease, individuals may present with splenomegaly with sea-blue histiocytes, hypertriglyceridemia, and thrombocytopenia, and preventive measures and surveillance related to cardiac manifestations may be beneficial, and knowledge that splenectomy can exacerbate hypertriglyceridemia may additionally be advantageous	4242937; 4195998; 6795720; 6289314; 6860421; 6323533; 3721502; 3771793; 3029073; 3038959; 3243553; 2539388; 2556398; 2313204; 2341812; 1864973; 1674745; 1713245; 1360898; 1361196; 1356443; 8488843; 7635945; 7586659; 9176854; 11095479; 15630634; 16094309; 16143024; 16431249; 16690468; 18077821; 20534298; 21534236; 22069485; 22481068; 22949395 
APOPT1	20492	84334	Mitochondrial complex IV deficiency	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	25175347
APP	620	351	Alzheimer disease, familial; Cerebral amyloid angiopathy	AD/AR	N/A	N/A	Cardiovascular; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2111584; 1679289; 1944558; 1671712; 1925564; 1678058; 1303275; 1303239; 1415269; 1520398; 1302033; 1642228; 8290042; 8154870; 9328472; 9754958; 10097173; 10441572; 11063718; 10821838; 11409420; 11528419; 12034808; 15365148; 15668448; 16033913; 16505331; 16369530; 16685645; 17325276; 18413473; 19047566; 19286555; 19225789; 22491860; 22702962; 22801501; 22815225; 23102935 
APRT	626	353	Adenine phosphoribosyltransferase deficiency	AR	Pediatric		Biochemical; Musculoskeletal; Renal	Biochemical; Renal		Medical and dietary interventions (eg, purine-restricted diet with adequate hydration and allopurinol or febuxostat, in instances where allopurinol can not be used) may be beneficial in order to decrease the severity of manifestations including nephrolithiasis and renal sequelae, as well as to treat individuals with relatively advanced disease; Renal transplant has been described, and disease-specific considerations (eg, immediate postoperative pharmacotherapy) may impact transplant outcomes	5676523; 5763607; 4852180; 1061547; 7766; 865583; 420519; 7311997; 6701033; 3876264; 3680503; 1353080; 806829; 3077470; 3409638; 3343350; 1986109; 1985452; 1353080; 1349689; 1349687; 7915931; 8825602; 9298830; 9521589; 11532677; 14767036; 15025810; 15077874; 15571218; 17126311; 19435978; 20101413; 20150536; 20303634; 20553441; 21635362; 22212387; 22934314; 22988602; 23430916
APTX	15984	54840	Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia	AR	N/A	N/A	Gastrointestinal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3239952; 11586299; 11586300; 11294920; 12196655; 14506070; 12629250; 15365154; 15596775;15852392; 15699391; 17572444; 17242337; 18403580; 21465257; 21486904
AQP1	633	358	Blood group, Colton	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	7521540; 7521882; 11606828; 11463012; 11773634
AQP2	634	359	Diabetes insipidus, nephrogenic, autosomal	AD/AR	Pediatric		Endocrine; Renal	Endocrine; Renal		Individuals can present in infancy with hypernatremia and severe dehydration, and recognition may allow preventive measures and prompt treatment	1828422; 8140421; 7524315; 9649557; 16845277
AQP3	636	360	Blood group, GIL	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	12239222
AR	644	367	Androgen insensitivity; Androgen insensitivity, partial	XL	Pediatric	Allelic with Spinal and bulbar muscular atrophy, X-linked 1 (XL) (a trinucleotide repeat disorder); Hypospadias 1, X-linked (XL)	Endocrine; Genitourinary; Neurologic; Oncologic	Endocrine; Oncologic; Genitourinary		Treatment with testosterone, starting at an early age may enable fertility; Surveillance for breast cancer may be beneficial	4233749; 4821173; 176660; 876326; 6801070; 2062380; 1303283; 759869; 1449253; 1598912; 1303262; 8469342; 8092978; 7937057; 7673412; 7702080; 8683794; 10999816; 11549642; 11238515; 12161529; 11788615; 11788616; 12221177; 15472213; 15242343; 22334387 
ARFGEF2	15853	10564	Heterotopia, periventricular, autosomal recessive	AR	N/A	N/A	Neurologic	General	In addition to neurologic manifestations, cardiomyoptathy and frequent infections have been described, but this finding may be coincidental; Recurrent infections have been described in several individuals, but it is unclear if this is a primary manifestation or secondary to neurodegenerative sequelae	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12682315; 14647276; 23755938
ARG1	663	383	Hyperargininemia	AR	Pediatric		Biochemical; Neurologic	Biochemical; Pharmacogenomic		Dietary and medical therapy (eg, with low-protein, arginine restricted diet, sodium benzoate), may be beneficial; Individuals with more severe and earlier presentations (similar to that of other urea cycle disorders) have been reported, and may benefit from similar care to prevent and acute sequelae; Individuals with urea cycle disorders may demonstrate sensitivity to certain agents, such as valproate	1124944; 839368; 624188; 6422160; 3104676; 2913054; 2311630; 2365823; 2246859; 2291040; 8474825; 7649538; 9762606; 12640389; 16963300; 19052914; 19381865; 21229317; 21802329; 21310339; 22959135; 22928720; 22633632 
ARHGAP31	29216	57514	Adams-Oliver syndrome 1	AD	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	474617; 16451141; 19610107; 21565291
ARHGDIA	678	396	Nephrotic syndrome, type 8	AR	N/A	N/A	Renal	General	Renal transplant has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23434736; 23867502
ARHGEF10	14103	9639	Slowed nerve conduction velocity, autosomal dominant (Hereditary motor and sensory neuropathy)	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9678704; 14508709
ARHGEF6	685	9459	Mental retardation, X-linked 46	XL	N/A	N/A	Neurologic	General	The evidence of mutations as being related to disease causation has been questioned due to subsequent population-based studies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9783701; 11017088; 23871722
ARHGEF9	14561	23229	Epileptic encephalopathy, early infantile, 8	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15215304; 21633362; 22612257
ARID1A	11110	8289	Mental retardation, autosomal dominant 14; Coffin-Siris syndrome	AD	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22426308; 22426309
ARID1B	18040	57492	Mental retardation, autosomal dominant, 12; Coffin-Siris syndrome	AD	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22405089; 22426308; 22426309
ARL13B	25419	200894	Joubert syndrome 8	AR	N/A	N/A	Neurologic; Ophthalmologic; Renal	General		The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18674751; 20615230; 22241855
ARL2BP	17146	23568	Retinitis pigmentosa with or without situs inversus	AR	N/A	N/A	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Ophthalmologic	General	Although described patients did not suffer from sequelae as severe as have been reported in other types of ciliary dyskinesia, similar medical interventions may in theory be warranted	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23849777
ARL6	13210	84100	Retinitis pigmentosa 55; Bardet Biedl syndrome 3	AR	N/A	N/A	Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	BBS3 may involve multiple congenital anomalies; Variants may modify severity of BBS due to mutations in other BBS-associated genes	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7987310; 9714014; 15258860; 15314642; 19956407; 19858128; 20301537; 23219996
ARL6IP1	697	23204	Spastic paraplegia 61	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24482476
ARMC4	25583	55130	Ciliary dyskinesia, primary, 23	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	23849778; 24203976
ARMC5	25781	79798	ACTH-independent macronodular adrenal hyperplasia 2	AD	Adult		Endocrine; Oncologic	Endocrine; Oncologic	Germline mutations in this tumor suppressor gene may result in the clinical phenotype in the presence of a second, somatic mutation	Surveillance for neoplasms, can allow early detection and treatment, which can involve surgical excision of the neoplasm or medical management (eg, targeting aberrant receptor expression) to control cortisol production	19018784; 24283224; 24601692; 24708098; 24905064
ARNT2	16876	9915	Webb-Datani syndrome	AR	Pediatric		Craniofacial; Endocrine; Neurologic; Ophthalmologic; Renal	Endocrine; Renal		The condition may involve multiple pituitary hormone deficiencies, and awareness may allow early recognition and treatment; Awareness of the risk of renal manifestations such as hydronephrosis and vesicoureteral reflux may allow surveillance and renal-protective measures	24022475
ARSA	713	410	Metachromatic leukodystrophy	AR	N/A	N/A	Biochemical; Neurologic	General	The condition can involve multiple congenital anomalies; BMT and CBT have been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21611375; 5828490; 14206875; 5642751; 5751920; 5367045; 4192207; 2863494; 2876627; 3813937; 1676699; 1678251; 1684088; 1673113; 1673291; 1670590; 15710861; 16966551; 18786133; 19067349
ARSB	714	411	Mucopolysaccharidosis type VI (Maroteaux-Lamy)	AR	Pediatric		Biochemical; Cardiovascular; Musculoskeletal; Ophthalmologic	Biochemical; Cardiovascular		Enzyme replacement therapy is available; The condition can include cardiovascular manifestations, and awareness may allow surveillance and early detection, which may lead to improved management; BMT has been reported	14091597; 6767429; 6776877; 6225949; 6150438; 1832719; 1718978; 1550123; 1301949; 1728449; 8651289; 10070618; 10036316; 11668612; 15324318; 15823680; 15690405; 17643332; 17671068; 21637564; 21930407; 21744090; 22127392;  22669363; 22278137; 22704873; 22864057; 21917494; 22938833; 22133300; 22336888; 22971959; 22495825; 22976768; 23023219; 22405600; 22395531 
ARSE	719	415	Chondrodysplasia punctata 1, X-linked recessive 	XL	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	Musculoskeletal		Individuals may demonstrate cervical spine stenosis and/or instability, and surveillance may be beneficial to detect and treat (eg, with placement of a cervical collar or spinal fusion) spinal sequelae	7720070; 9863597; 12567415; 18348268; 20301713; 20523025; 23462608; 23470839
ART4	726	420	Blood group, Dombrock	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	8036791; 9838931; 11001920; 11724986; 12130524; 12028057
ARX	18060	170302	Partington X-linked mental retardation syndrome; Epileptic encephalopathy, early infantile, 1; Lissencephaly, X-linked 2; Hydranencephaly with abnormal genitalia; Mental retardation, X-linked 29/32/33/38/43/54/76/87; Proud syndrome; Corpus callosum, agenesis of, with abnormal genitalia	XL	N/A	N/A	Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	Pharmacogenomic; General	Conditions can involve multiple congenital anomalies; monitoring for ophthalmologic complications during systemic steroid therapy has been advised	Due to potential ophthalmologic complications, monitoring considerations may be important during corticosteroid therapy; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3177452; 1605226; 8826464; 9001795; 8826462; 9307258; 10334471; 10398246; 10398242; 10398243; 10353782; 11971879; 11891829; 12485186; 12379852; 12116222; 12177367; 11889467; 12689911;14722918; 15200506; 15850492; 17082467; 17664401; 17668384; 18462864; 19439424; 19738637; 21108397; 21426321; 22490986; 22585566; 22922607; 23039062; 23072184
ASAH1	735	427	Farber lipogranulomatosis	AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic; Pulmonary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13859108; 6423791; 2983648; 2854742; 3103372; 3130860; 8955159; 8892023; 11241842
ASCC1	24268	51008	Barrett esophagus/Esophageal adenocarcinoma	AD	Adult		Gastrointestinal; Oncologic	Gastrointestinal; Oncologic		Awareness of disease risk may allow surveillance, preventive measures (eg, related to Barrett esophagus) and early treatment of malignancy, which may reduce morbidity and mortality	21791690
ASCL1	738	429	Central hypoventilation syndrome, congenital (Haddad syndrome)	AD	Pediatric		Neurologic	Neurologic		Early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality	14532329
ASIP	745	434	Skin/hair/eye pigmentation 9	AD	N/A	N/A	Dermatologic	General		The clinical relevance is unclear, though variants may be related to susceptibility to melanoma	11833005; 18488028
ASL	746	435	Argininosuccinic aciduria	AR	Pediatric		Biochemical; Dermatologic; Neurologic	Biochemical; Pharmacogenomic		Dietary and medical therapy (eg, with low-protein diet supplemented with arginine), may be beneficial, and special care to prevent/treat acute metabolic decompensation (eg, with IV glucose and ammonia-reducing agents) may be effective; Certain agents (such as enflurane, an anesthetic agent) should be avoided due to reports of adverse reactions	13503250; 5836520; 84150; 2263616; 1897577; 1594374; 9504797; 12408190; 12384776; 17326097; 22541557; 20236848; 19635676; 22541557; 22841516; 23040521 
ASNS	753	440	Asparagine synthetase deficiency	AR	Pediatric		Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24139043
ASPA	756	443	Aspartoacylase deficiency (Canavan disease)	AR	N/A	N/A	Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2512436; 8252036; 8023850; 10909858; 12638939; 16437572; 18070137
ASPH	757	444	Facial dysmorphism, lens dislocation, anterior segment abnormalities, and spontaneous filtering blebs (FDLAB)	AR	Pediatric		Craniofacial; Ophthalmologic	Ophthalmologic		Early surgical removal of the lens has been reported as necessary in order to preserve visual function by preventing irreversible corneal and trabecular meshwork damage	11241487; 23687502; 24768550
ASPM	19048	259266	Microcephaly, primary autosomal recessive, 5	AR	N/A	N/A	Neurologic	General	Frequent infections have been described, but it is not clear if these are intrinsic to the disorder or secondary to neurologic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed med	12355089; 14574646; 16673149; 18452193; 19353628; 19028728; 19770472
ASS1	758	445	Citrullinemia 	AR	Pediatric		Biochemical; Gastrointestinal; Neurologic	Biochemical; Pharmacogenomic		To prevent decompensation, medical therapy (eg, with sodium phenylbutyrate, L-carnitine) and dietary management (including avoidance of excess protein) can be beneficial, especially in high-risk states such as during infectious episodes; In the acute state, control of hyperammonemia (eg, with sodium benzoate/phenylacetate or emergent hemodialysis, with dietary measures to prevent catabolism) with steps to prevent increased intracranial pressure can be beneficial; Avoidance of certain agents (eg, valproate) is warranted due to potential adverse events	934749; 6807193; 3459354; 2358466; 3148074; 2246861; 7977368; 7557970; 11571557; 11804205; 11941481; 15334737; 15266621; 19006241; 20142522; 20301631; 22494546; 22594780; 22768672; 23099195; 23246278; 23430935; 23611581
ASXL1	18318	171023	Bohring-Opitz syndrome	AD	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21706002; 22419483
ASXL3	29357	80816	Bainbridge-Ropers syndrome	AD	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23383720
ATCAY	779	85300	Ataxia, cerebellar, Cayman type	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14556008
ATIC	794	471	AICAR transformylase/IMP cyclohydrolase deficiency	AR	N/A	N/A	Biochemical; Dermatologic; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15114530
ATL1	11231	51062	Neuropathy, hereditary sensory, type 1D; Spastic paraplegia 3A, autosomal dominant	AD	N/A	N/A	Neurologic	General	Congenital insensitivity to pain can result in injuries and infections	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11685207; 12112092; 15517445; 15596607; 16401858; 16533974; 17502470; 21194679; 21336785
ATL3	24526	25923	Neuropathy, hereditary sensory, type IF	AD	N/A	N/A	Neurologic	General	Insensitivity to pain can result in injuries and infections	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24459106
ATM	795	472	Breast cancer, susceptibility to; Ataxia-Telangiectasia	AD/AR	Pediatric (Ataxia-Telangiectasia); Adult (Breast cancer, susceptibility to)		Allergy/Immunology/Infectious; Neurologic; Oncologic; Ophthalmologic	Allergy/Immunology/Infectious; Oncologic	Though the evidence is overall difficult to interpret, heterozygotes may be at increased risk of a number of types of malignancies	For breast cancer, susceptibility to, awareness of the risk of malignancy may allow surveillance, preventive measures, and early diagnosis and treatment; In Ataxia-Telangiectasia, for infectious complications, prophylaxis and early and aggressive treatment of infections can be beneficial; Surveillance for malignancy can be beneficial; Precautions should be taken related to ionizing radiation and chemotherapeutic regimens (eg, related to dosage)	311128; 4515676; 4132004; 310962; 7124732; 3496017; 3785360; 3788973; 3574400; 2916583; 2136770; 2253179; 2005780; 1961222; 1304718; 1377828; 8365732; 7836845; 7792600; 8976369; 9054927; 9259193; 9054948; 9463314; 10571946; 10425038; 9887333; 10677309; 10980530; 11826028; 12226795; 12552559; 15942625; 16864838; 16832357; 19535770; 19440741; 20301790; 21429505; 23264026; 23612382; 23900766; 25186627; 25330149
ATN1	3033	1822	Dentatorubro-pallidoluysian atrophy	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6808417; 2742549; 7951323; 8136840; 8041369; 7477999; 8644735; 9568927; 11160976; 15948186
ATOH7	13907	220202	Retinal nonattachment, nonsyndromic congenital	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9677055; 21441919
ATP13A2	30213	23400	Parkinson disease 9 (Kufor-Rakeb syndrome)	AR	N/A	N/A	Neurologic	General	Response to levodopa has been documented	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16964263; 17485642; 20310007
ATP1A2	800	477	Alternating hemiplegia of childhood; Migraine, familial hemiplegic 2	AD/AR	Pediatric	Allelic with Migraine, familial hemiplegic, 2 (AD); Migraine, familial basilar (AD)	Neurologic	Neurologic; Pharmacogenomic		In Alternating hemiplegia of childhood, medical treatment (with calcium channel blockers) has been described as at least partially effective; Vasoconstricting agents (due to risk of stroke) and cerebral angiograophy (due to risk of precipitation of attack) should be avoided	9579893; 12539047; 12953268; 14667076; 14636773; 14636773; 15159495; 15174025; 15210532; 15286158; 15459825; 15985592; 16437583; 16344534;  16538223; 17142831; 17473835; 18056581; 18028456;  18846413; 20301562; 20837964; 21352219; 22759692; 23203776; 23838748; 23918834
ATP1A3	801	478	Alternating hemiplegia of childhood 2	AD	Pediatric	Allelic with Dystonia 12 (AD); Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome (AD)	Audiologic/Otolaryngologic; Neurologic; Ophthalmologic	Neurologic	In Dystonia 12, reports indicate limited efficacy of levodopa treatment	Medical treatment with calcium channel blockers has been described as beneficial (though not curative) for treatment of the hemiplegic attacks in the majority of individuals patients	8733056; 15260953; 17282997; 19652145; 20558373; 22842232; 22850527; 22857851; 22924536; 23409136; 24468074; 24842602
ATP2A1	811	487	Brody myopathy	AR	Pediatric		Musculoskeletal	Musculoskeletal		Individuals typically present with exercise-induced muscle relaxation impairment, with, stiffening, cramps, and muscle pain, and medical management (eg, with dantrolene or verapamil) has been described as beneficial in some individuals	1405485; 8040329; 8841193; 9367679; 10914677; 20142766 
ATP2A2	812	488	Darier disease; Acrokeratosis verruciformis (Hopf disease)	AD	N/A	N/A	Dermatologic	General	In Darier disease, oral retinoids may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	921905; 1619075; 10441324; 10080178; 10441323; 11121153; 12542527; 12925205; 14675181; 22004489; 22035154; 22329366; 22814319; 22909361 
ATP2B3	816	492	Spinocerebellar ataxia, X-linked 1	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10797423; 22912398
ATP2C1	13211	27032	Pemphigus, benign familial; Hailey-Hailey disease	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4939904; 5093171; 3978039; 2528572; 1554604; 1575528; 10615129; 15545997; 21623880; 21883398; 22124882; 22229453; 22607350; 22788811 
ATP5A1	823	498	Combined oxidative phosphorylation deficiency 22; Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4	AR	N/A	N/A	Biochemical; Cardiovascular; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23596069; 23599390
ATP5E	838	514	Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18953340; 20566710
ATP6AP2	18305	10159	Mental retardation, X-linked, syndromic, Hedera type; Parkinsonism with spasticity, X-linked	XL	N/A	N/A	Musculoskeletal; Neurologic	General	The evidence of mutations as being related to disease causation has been questioned due to subsequent population-based studies; In Parkinsonism, response to l-dopa has been reported	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11782983; 15746149; 20629132; 23595882; 23871722
ATP6V0A2	18481	23545	Cutis laxa, autosomal recessive, type IIA; Wrinkly skin syndrome	AR	N/A	N/A	Biochemical; Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15657616; 18157129; 17971833; 19401719; 22773132 
ATP6V0A4	866	50617	Renal tubular acidosis, distal, autosomal recessive	AR	Pediatric		Audiologic/Otolaryngologic; Renal	Renal		Alkali replacement can reverse most biochemical abnormalities, and may be effective, especially in severe cases, to prevent eventual renal insufficiency	10973252; 12414817
ATP6V1B1	853	525	Renal tubular acidosis with deafness	AR	Pediatric		Audiologic/Otolaryngologic; Renal	Renal		Individuals can present in infancy with acute with dehydration (which can be lethal), which can be prevented by early recognition	9916796; 12414817; 12566520; 16433694; 18798332
ATP7A	869	538	Menkes disease	XL	Pediatric	Allelic with Occipital horn syndrome (XL); Spinal muscular atrophy, distal, X-linked 3 (XL)	Biochemical; Cardiovascular; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	Biochemical; Renal		With early diagnosis, daily copper injections may be beneficial (SQ injections before 10 days of life have been reported as resulting in improvement of neurologic outcome); Individuals may be prone to urinary tract infections, and measures such as antibiotic prophylaxis may be beneficial	14472668; 5045346; 1218238; 953234; 6104292; 6140952; 4075564; 2839049; 2512453; 8490646; 8490647; 8490659; 8099605; 7842019; 8149649; 7887410; 8923001; 8528242; 9111998; 9138147; 9511979; 9894833; 14635105; 14985388; 15981243; 16630173; 17108763; 18256395; 19153371; 20652413; 20301586; 20170900; 22992316; 22711717; 22695177; 21221114 
ATP7B	870	540	Wilson disease	AR	Pediatric		Biochemical; Gastrointestinal; Neurologic; Ophthalmologic	Biochemical; Gastrointestinal		Dietary measures (eg, avoidance of copper-containing foods), as well as medications (eg, penicillamine, zinc, vitamin B6, tetrathiomolybdate), and possible liver transplant, can be beneficial	463930; 3900322; 3561699; 3328213; 8298639; 8298641; 8201263; 7884606; 8610495; 9794697; 10435491; 10435489; 10673307; 12376745; 12633149; 12756138; 16283883; 16216950; 20301685; 16606763; 21901655; 22327203; 21832955; 22083169 
ATP8B1	3706	5205	Familial intrahepatic cholestasis, recurrent; Cholestasis, progressive familial intrahepatic 1; Intrahepatic cholestasis of pregnancy	AD/AR	Pediatric	Allelic with Benign recurrent intrahepatic cholestasis (AD/AR)	Gastrointestinal; Obstetric	Gastrointestinal; Obstetric 		In severe forms, specific nutritional care may be beneficial (eg, including specific vitamin E supplementation);  Hepatic manifestations may result in death in adolescence/early adulthood without surgical intervention; In pregnancy, Cholestasis, familial intrahepatic, of pregnancy, can cause severe sequelae (including death) in the fetus, as well as adverse maternal health outcomes, and precautions, including early delivery may be beneficial	13840084; 5807632; 5762004; 5049818; 1218817; 3564958; 8088298; 7912266; 9500542; 9918928; 11093741; 15239083; 15448432; 15888793; 15657619; 20301474 
ATPAF2	18802	91647	Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1	AR	N/A	N/A	Biochemical; Cardiovascular; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14757859; 20566710 
ATR	882	545	Cutaneous telangiectasia and cancer syndrome, familial; Seckel syndrome 1	AD/AR	Pediatric		Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic; Oncologic	Oncologic		Though both Seckel syndrome 1 and Cutaneous telangiectasia and cancer syndrome, familial are potentially recognizable, surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of oncologic manifestations, which may reduce morbidity and mortality 	13869653; 6022184; 4378248; 7046443; 8358044; 8182723; 9128935; 10889046; 12640452; 22341969; 23111928
ATRX	886	546	Mental retardation-hypotonic facies syndrome, X-linked; Juberg-Marsidi syndrome; Carpenter-Waziri syndrome; Holmes-Gang syndrome; Smith-Fineman-Myers syndrome; Alpha-thalassemia/mental retardation syndrome 	XL	N/A	N/A	Craniofacial; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6267462; 6682021; 6711605; 3239563; 1684092; 7726225; 8644709; 10398237; 10398234; 11449489; 11050622; 10751095; 15508018; 16222662; 16100724; 16813605; 16955409; 16688741; 17579672; 19764021; 20301622; 22089611 
ATXN1	10548	6310	Spinocerebellar ataxia 1	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8275090; 8358429; 7951322; 8198139; 8037204; 8615077; 10424816; 11973625; 14967775; 16133185; 15747371; 18262566; 18685131; 20301363 
ATXN10	10549	25814	Spinocerebellar ataxia 10	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11017075; 11506407; 15127363; 16717236; 17420323; 20301354; 20818609; 21236683; 21531163 
ATXN2	10555	6311	Spinocerebellar ataxia 2	AD	N/A	N/A	Neurologic	General	In some individuals, the phenotype may include L-dopa responsive parkinsonism; Homozygosity/compound heterozygosity has been reported	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8896557; 8896555; 8896556; 10735276; 9779806; 10993999; 11761482; 12210804; 12451209; 12671950; 15254952; 14732617; 15747371; 17568014; 17923635; 19676102; 20301452; 21610160; 21562247; 21880993; 21934711
ATXN3	7106	4287	Spinocerebellar ataxia 3 (Machado-Joseph disease)	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5061839; 865531; 7874163; 7573040; 7496771; 7795637; 7633439; 7561932; 7655453; 8619527; 8640226; 9403486; 11176969; 15457499; 15747371; 20301375; 21555642; 21635785; 22023810
ATXN7	10560	6314	Spinocerebellar ataxia 7	AD	N/A	N/A	Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7477379; 8908515; 9288099; 9536097; 9736784; 10330346; 10453742; 11030806; 15349877; 15750685; 15747371; 20301433; 23368522
ATXN8	32925	724066	Spinocerebellar ataxia 8	AD	N/A	N/A	Neurologic; Ophthalmologic	General	The causative expansion mutation is located in both the ATXN8OS 3' UTR and a polyglutamine ORF in ATXN8	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16804541
ATXN8OS	10561	6315	Spinocerebellar ataxia 8	AD	N/A	N/A	Neurologic; Ophthalmologic	General	The causative expansion mutation is located in both the ATXN8OS 3' UTR and a polyglutamine ORF in ATXN8	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10192387; 14756671;  16804541; 19680539; 20301445; 20403608
AUH	890	549	3-methylglutaconic aciduria, type I	AR	N/A	N/A	Biochemical; Neurologic	General	Dietary measures (leucine restriction) have been suggested	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	720359; 3082934; 1710267; 1375542; 9762598; 10070612; 12434311; 15033206; 16354225; 17130438; 20855850; 21840233 
AURKC	11391	6795	Spermatogenic failure 5	AR	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17435757; 19147683; 21733974; 22888167
AUTS2	14262	26053	Mental retardation, autosomal dominant 26	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22872102; 23332918
AVP	894	551	Diabetes insipidus, neurohypophyseal	AD/AR	Pediatric		Endocrine; Renal	Endocrine; Renal		Treatment/prevention of hypernatremia can be effective;  Medications related to osteoporosis/osteopenia may be beneficial	10404801; 10369876; 14673472; 15070970; 22524462 
AVPR2	897	554	Diabetes insipidus, nephrogenic, X-linked	XL	Pediatric		Endocrine; Renal	Endocrine; Renal		Severe sequelae including neonatal seizures and infant death secondary to dehydration has been reported, and such  sequelae could be prevented with early genetic knowledge; Therapies include electrolyte correction (eg, with fluid restriction, osmotic agents, as well as medications such as hydrochlorothiazide) 	13644230; 3970081; 3080575; 1356229; 1303271; 8104196; 9329382; 10477148; 15872203; 16845277; 22722264 
AXIN1	903	8312	Caudal duplication anomaly	AD/Methylation	N/A	N/A	Gastrointestinal; Genitourinary; Musculoskeletal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12376942; 16773576
AXIN2	904	8313	Oligodontia-colorectal cancer syndrome	AD	Adult	Allelic with Oligondontia, isolated (AD)	Dental; Oncologic	Oncologic	Some individuals may appear to have dental anomalies without obviously increased colorectal cancer risk	Although the condition may be clinically recognizable in many individuals, the oncologic risk may not be clear, and awareness may allow surveillance for and early treatment of related malignancies (eg, breast cancer, colorectal cancer), which may reduce morbidity and mortality	15042511; 21626677; 21416598 
B2M	914	567	Hypoproteinemia, hypercatabolic 	AR	Pediatric	Allelic with Amyloidosis, systemic visceral (AD) (In amyloidosis, liver transplantation may be beneficial, but it is not clear if early (genetic) diagnosis would be beneficial)	Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Neurologic; Renal	Allergy/Immunology/Infectious		Individuals can have immunodeficiency, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	4186801; 2254461; 16549777; 22693999 
B3GALNT1	918	8706	Blood group, P system	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	12023287
B3GALNT2	28596	148789	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 11	AR	N/A	N/A	Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23453667
B3GALT6	17978	126792	Ehlers-Danlos syndrome, progeroid type, 2; Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures	AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23664117; 23664118
B3GALTL	20207	145173	Peters-plus syndrome	AR	Pediatric		Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	Ophthalmologic	The condition can involve multiple congenital anomalies	Individuals may be at high risk for ophthalmologic complications, including glaucoma, and surveillance may allow early interventions and management	16909395; 18199743; 18798333; 19796186; 20301637; 21067481; 21671750; 22759511 
B3GAT3	923	26229	Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects	AR	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21763480; 24668659
B4GALT1	924	2683	Congenital disorder of glycosylation, type IId	AR	Pediatric		Biochemical; Hematologic; Musculoskeletal; Neurologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	11901181; 11930273; 21920538 
B4GALT7	930	11285	Ehlers-Danlos syndrome, progeroid form	AR	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3631078; 10473568; 10506123; 15211654; 16583246; 20809901 
B4GAT1	15685	11041	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13	AR	N/A	N/A	Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23359570
B9D1	24123	27077	Meckel syndrome, type 9	AR	N/A	N/A	Genitourinary; Musculoskeletal; Neurologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21493627
B9D2	28636	80776	Meckel syndrome, type 10	AR	N/A	N/A	Gastrointestinal; Musculoskeletal; Neurologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21763481
BAAT	932	570	Hypercholanemia, familial	AR	Pediatric		Gastrointestinal	Gastrointestinal		Individuals may present with manifestations including pruritus, sequelae of fat malabsorption (which can be severe), and elevated serum bile acid concentrations, which typically respond to medical treatment (eg, with ursodeoxycholic acid and fat-soluble vitamins)	12704386; 22783059 
BAG3	939	9531	Cardiomyopathy, dilated, 1HH; Myopathy, myofibrillar 6	AD	Adult		Cardiovascular; Musculoskeletal; Neurologic	Cardiovascular		In Dilated cardiomyopathy, surveillance (eg, with echocardiogram and electocardiogram) may allow early detection and management of manifestations, which may be beneficial; In Myofibrillar myopathy, individuals typically present with slowly progressive weakness, and a significant proportion of individuals demonstrate cardiomyopathy, such that surveillance for arrhythmia or conduction defects may allow early treatment (eg, pacemaker, ICD); Cardiac transplantation may be necessary individuals with severe forms of cardiomyopathy; Heart transplant has been described	16936253; 19085932; 20301672; 21898660; 21256014; 21353195; 21361913; 21459883; 25208129
BANF1	17397	8815	Nestor-Guillermo progeria syndrome	AR	N/A	N/A	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21932319; 21549337
BAP1	950	8314	Tumor predisposition syndrome	AD	Pediatric		Dermatologic; Oncologic	Dermatologic; Oncologic		Awareness of oncologic risk may allow surveillance for and early treatment of a variety of malignancies (including uveal and cutaneous melanomas, mesothelioma, and several other types of cancer), which may reduce morbidity and mortality	21941004; 21874000 21874003; 23032617; 23341325 
BARD1	952	580	Breast cancer, susceptibility to	AD	Adult		Oncologic	Oncologic		Though the availability of empirical data is incomplete as applies to both screening strategies and prophylactic treatment, surveillance may allow early detection and management of cancer	14550946; 16768547; 16825437; 17333333; 24549055; 25058500
BBIP1	28093	92482	Bardet-Biedl syndrome 18	AR	N/A	N/A	Gastrointestinal; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition frequently involves multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24026985
BBS1	966	582	Bardet-Biedl syndrome 1	AR 	N/A	N/A	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Variants may modify the severity of BBS and related disorders due to mutations in other BBS-associated genes; The condition frequently involves multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12118255; 12567324; 12677556; 12837689; 12524598; 15314642; 20120035; 20301537; 22410627; 22773737; 22940089; 23143442
BBS10	26291	79738	Bardet-Biedl syndrome 10	AR 	N/A	N/A	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Variants may modify the severity of BBS and related disorders due to mutations in other BBS-associated genes; The condition frequently involves multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16823392; 16582908; 20120035; 20301537; 20805367; 22410627
BBS12	26648	166379	Bardet-Biedl syndrome 12	AR 	N/A	N/A	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Variants may modify the severity of BBS and related disorders due to mutations in other BBS-associated genes; The condition frequently involves multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17160889; 20827784; 20120035; 20301537; 22410627
BBS2	967	583	Bardet-Biedl syndrome 2	AR 	N/A	N/A	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Variants may modify the severity of BBS and related disorders due to mutations in other BBS-associated genes; The condition frequently involves multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8298649; 11285252; 11567139; 16823392; 16582908; 20120035; 20301537; 20618352; 22410627
BBS4	969	585	Bardet-Biedl syndrome 4	AR 	N/A	N/A	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Variants may modify the severity of BBS and related disorders due to mutations in other BBS-associated genes; The condition frequently involves multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7711739; 11381270; 12016587; 15654695; 20301537; 22219648
BBS5	970	129880	Bardet-Biedl syndrome 5	AR 	N/A	N/A	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Variants may modify the severity of BBS and related disorders due to mutations in other BBS-associated genes; The condition frequently involves multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15137946; 18203199; 20301537; 22410627
BBS7	18758	55212	Bardet-Biedl syndrome 7	AR 	N/A	N/A	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Variants may modify the severity of BBS and related disorders due to mutations in other BBS-associated genes; The condition frequently involves multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12567324; 21937992; 20301537;  22410627
BBS9	30000	27241	Bardet-Biedl syndrome 9	AR	N/A	N/A	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Variants may modify the severity of BBS and related disorders due to mutations in other BBS-associated genes; The condition frequently involves multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16380913; 20301537
BCAM	6722	4059	Blood group, Lutheran system; Blood group, Auberger system; Lutheran, null	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	14025138; 4836779; 1146276; 9192786; 9166867; 17319831; 18487511
BCAP31	16695	10134	Deafness, dystonia, and cerebral hypomyelination	XL	N/A	N/A	Audiologic/Otolaryngologic; Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24011989
BCHE	983	590	Butyrlcholinesterase deficiency	AR	Pediatric		Biochemical	Pharmacogenomic		Individuals have prolonged apnea upon use of specific anesthetics (ie, suxamethonium, succinylcholine)	13711731; 14465122; 4984470; 3741370; 3225823; 2915989; 2911599; 2013061; 1662391; 1349196; 1415224; 8554068; 9543549; 9302273; 9110359; 9388484; 10190327; 10699053; 12881446; 16788378; 18075469; 18555211; 21029050 
BCKDHA	986	593	Maple syrup urine disease, type Ia	AR	Pediatric		Biochemical; Neurologic	Biochemical		Dietary measures (eg, leucine restriction, high-calorie branched chain amino acid-free formulas, isoleucine and valine supplementation) combined with careful surveillance can be beneficial to prevent decompensation and minimize disease sequelae; specific treatment in times of metabolic decompensation can reduce morbidity and mortaility; Liver transplantation is effective for classic MSUD; Specific monitoring is indicated in pregnancy	8037208; 7883996; 7672509; 11112664; 12042535; 14567968;  14742428; 17922217; 18378174; 20301313; 20301495; 20061171; 22326532 
BCKDHB	987	594	Maple syrup urine disease, type Ib	AR	Pediatric		Biochemical; Neurologic	Biochemical		Dietary measures (eg, leucine restriction, high-calorie branched chain amino acid-free formulas, isoleucine and valine supplementation) combined with careful surveillance can be beneficial to prevent decompensation and minimize disease sequelae; specific treatment in times of metabolic decompensation can reduce morbidity and mortaility; Liver transplantation is effective for classic MSUD; Specific monitoring is indicated in pregnancy	2022752; 11509994; 11112664; 14567968; 17922217; 20301495; 22326532 
BCKDK	16902	10295	Branched-chain ketoacid dehydrogenase kinase deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		Individuals may present with features such as autism and epilepsy, and though not definitely proven, there is strong evidence that dietary supplementation (eg, with branched chain amino acids) may be beneficial 	22956686
BCL10	989	8915	Immunodeficiency 37	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Indiividuals have been described as susceptible to severe infections, and awareness may allow preventive measures and early and aggressive treatment of infections	25365219
BCL11A	13221	53335	Severe speech sound disorder	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24810580
BCO1	13815	53630	Hypercarotenemia and vitamin A deficiency, autosomal dominant	AD/AR	Pediatric		Biochemical	Biochemical; Gastrointestinal		Dietary precautions may be beneficial, as individuals may have manifestations of hypercarotenemia/hypovitaminosis A with a carotenoid-containing/retinol-inadequate diet	5453458; 17951468
BCOR	20893	54880	Microphthalmia, syndromic 2; Oculofaciocardiodental syndrome	XL	N/A	N/A	Cardiovascular; Craniofacial; Dental; Gastrointestinal; Genitourinary; Ophthalmologic; Musculoskeletal; Renal	General	The condition can involve multiple congenital anomalies	The condition can include cardiovascular, renal, and other anomalies; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13963827; 1225823; 10069716; 15004558; 15770227; 15957158; 20301694; 21740180; 22301464 
BCR	1014	613	CML treatment, response to	AD	Pediatric		General	Pharmacogenomic		Homologous mutations (to T315I in ABL) in BTK and TEC mutations may confer resistance to dasatinib; Certain variants appear to confer STI571 resistance in CML treatment	11423618; 12654249; 14534339; 17684099 
BCS1L	1020	617	Bjornstad syndrome	AR	Pediatric	Allelic with GRACILE syndrome (AR); Leigh syndrome (AR); Mitochondrial complex III deficiency, nuclear type 1 (AR), in which some treatment attempts (eg, with apotransferrin) have been reported, and treatment with "mitochondrial cocktail" type therapy may be beneficial	Audiologic/Otolaryngologic; Biochemical; Dermatologic; Gastrointestinal; Genitourinary; Neurologic; Ophthalmologic; Renal	Audiologic/Otolaryngologic	The condition includes frequently recognizable features such as hair anomalies (pili torti)	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; It has been suggested that  that stapes surgery should not be performed due to a high likelihood of complications (the use of cochlear implants has been reported as beneficial)	9482441; 10654962; 7577396; 10654962; 11528392; 12215968; 12910490; 17314340; 17403714; 19162478; 19389488; 19508421; 20580947; 20518024; 20472482; 22277166; 22991165 
BDNF	1033	627	Central hypoventilation syndrome, congenital	AD	Pediatric		Neurologic	Neurologic		Early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality	10390427; 11840487; 20301600 
BEAN1	24160	146227	Spinocerebellar ataxia 31	AD	N/A	N/A	Audiologic/Otolaryngologic; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17611710; 19878914
BEST1	12703	7439	Vitreoretinochoroidopathy; Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma 	AD	Adult	Allelic with  Macular dystrophy, vitelliform, adult-onset (AD); Retinitis pigmentosa 50 (AD); Macular dystrophy, vitelliform (AD); Best macular dystrophy (AD); Bestrophinopathy, autosomal recessive (AR)	Ophthalmologic	Ophthalmologic; Pharmacogenomic		Findings such as glaucoma and retinal detachment have been described, and surveillance and early treatment (eg, direct laser photocoagulation and anti-vascular endothelial growth factors for choroidal neovascularization and hemorrhage), as well as preventive measures, may be beneficial; Agents that may contribute to glaucoma, as well as smoking, should be avoided	13546939; 838599; 7065944; 6689931; 8431155; 9662395; 10453731; 10331951; 10854112; 10737974; 11585313; 12543751; 15452077; 16458719; 16678511; 17698758; 17591911; 18179881; 18611979; 19853238; 20057903; 20301346; 20375334; 20847757; 21192766; 21320969; 22422030; 22584882; 22633354; 23290749; 23572118; 23765342; 23823511; 24345323
BFSP1	1040	631	Cataract, cortical, juvenile-onset	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17225135
BFSP2	1041	8419	Cataract 12, multiple types	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10729115; 10739768; 10634598; 15570218; 17982427; 18958306; 21836522 
BHLHE41	16617	79365	Short sleeper	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19679812
BICC1	19351	80114	Renal dysplasia, cystic, susceptibility to	AD	Pediatric		Renal	Renal		Sequelae can include vesicoureteral reflux, and early diagnosis could be helpful to institute measures to preserve kidney function	21922595
BIN1	1052	274	Myopathy, centronuclear, 2	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17676042; 20142620; 22392505 
BLK	1057	640	Maturity-onset diabetes of the young, type 11	AD	N/A	N/A	Endocrine	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19667185
BLM	1058	641	Bloom syndrome	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic; Pulmonary	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Oncologic	Variants may also be related to risk of malignancy in the general poulation	Surveillance and early diagnosis of malignancy could potentially be beneficial; Avoidance of ionizing radiation/DNA-damaging chemicals (as well as sun exposure) can reduce morbidity; Individuals may be susceptible to infections, and prompt treatment, as well as control of gastroesophageal reflux, which can be contributory, can be beneficial	5923432; 7386453; 7273457; 6705251; 3040954; 3808032; 3808031; 2721026; 1809225; 7585968; 8875252; 9062585; 9285778; 10464606; 11477604; 12242432; 15137905; 17407155; 18471088; 18974064; 20301572; 21815139; 22514588; 23028338; 23443610; 24118499
BLNK	14211	29760	Agammaglobulinemia 4	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals can have immunodeficiency (which can involve frequent and severe infections, including reports of lethal bacterial sepsis) related to agammaglobulinemia, and antiinfectious prophylaxis (IVIG has been reported to be beneficial) and early and aggressive treatment of infections may be beneficial	10583958
BLOC1S3	20914	388552	Hermansky-Pudlak syndrome 8	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pharmacogenomic;  Pulmonary		Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination; Surveillance related to ophthalmologic, gastrointestinal, and other manifestations has been recommended in all individuals with HPS	16385460; 20301464 
BLOC1S6	8549	26258	Hermansky-Pudlak syndrome 9	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pharmacogenomic;  Pulmonary		Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination; Surveillance related to ophthalmologic, gastrointestinal, and other manifestations has been recommended in all individuals with HPS	21665000; 20301464; 22461475
BLVRA	1062	644	Hyperbiliverdinemia	AD/AR	N/A	N/A	Gastrointestinal	General	Appropriate hepatic-related care may be beneficial, but the advantage of genetic diagnosis is unclear; Individuals with heterozygous mutations have been reported as manifesting with clinical signs in the context of (apparently unrelated) liver dysfunction	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19580635; 19699374; 21278388
BMP1	1067	649	Osteogenesis imperfecta, type XIII	AR	N/A	N/A	Craniofacial; Musculoskeletal; Ophthalmologic	General	The use of bisphosphonates has been described, but it is unclear if an early (genetic) diagnosis would be advantageous	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22052668; 22482805
BMP15	1068	9210	Premature ovarian failure 4; Ovarian dysgenesis 2	XL	Pediatric		Endocrine; Genitourinary; Obstetric	Obstetric		Genetic knowledge may allow reproductive capabilities such as via egg preservation	15136966; 16508750; 19263482
BMP2	1069	650	Brachydactyly, type A2	AD	N/A	N/A	Musculoskeletal	General	The cause involves duplication of a downstream regulatory element of the gene	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7390514; 19327734; 21357617
BMP4	1071	652	Microphthalmia, syndromic 6; Orofacial cleft 11	AD	N/A	N/A	Craniofacial; Endocrine; Musculoskeletal; Neurologic; Renal; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18252212; 18305125; 19249007; 21340693
BMPER	24154	168667	Diaphanospondylodysostosis	AR	N/A	N/A	Craniofacial; Musculoskeletal; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20869035
BMPR1A	1076	657	Polyposis syndrome, hereditary mixed, 2; Polyposis, juvenile intestinal	AD	Adult		Oncologic	Oncologic		Surveillance (eg, with colonoscopy and endoscopic polypectomy, as well upper endoscopy for symptomatic indiviudlas, and monitoring for sequelae including anemia and rectal bleeding) may be beneficial, though partial/total colectomy/gastrectomy may be indicated in some individuals with a large polyp burden; Indivduals may have a variety of HHT-related vascular complications, including arteriovenous malformations, aortic dilatation, and bleeding diatheses, and surveillance and early intervention related to manifestations (eg, related to thromboembolism or hepatic disease) may decrease morbidity and mortality	5483654; 4544011; 7059958; 3707330; 8037173; 7582207; 11381269; 12136244; 15235019; 16152648; 16525031; 17873119; 20843829; 22171123;  22810475 
BMPR1B	1077	658	Chondrodysplasia, acromesomelic, with genital anomalies; Brachydactyly A2; Brachydactyly C/Symphalangism-like phenotype	AD/AR	N/A	N/A	Genitourinary; Musculoskeletal	General	Interventionss may be beneficial to allow reproductive capacity	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14523231; 15805157; 16957682
BMPR2	1078	659	Pulmonary hypertension, primary; Pulmonary venoocclusive disease 1	AD	Pediatric		Cardiovascular; Pulmonary	Cardiovascular; Pharmacogenomic; Pulmonary		While prognosis is overall poor, medical therapy (eg, with calcium antagonists, anticoagulants, prostanoids, endothelin receptor antagonists, etc.) may be beneficial, though heart/lung transplantation may be required; Control of complications may be beneficial; Exposure to agents such as fenfluramine has been described as greatly increasing the risk of disease	601742; 1863023; 10903931; 11115457; 10973254; 11015450; 12358323; 12446270; 16429403; 16429395; 15965979; 18356561; 20956135; 19749199; 19713419; 19555857; 21801371 
BMS1	23505	9790	Aplasia cutis congenita, nonsyndromic	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23785305
BOLA3	24415	388962	Multiple mitochondrial dysfunctions syndrome 2	AR	N/A	N/A	Biochemical; Cardiovascular; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11156534; 21944046; 22562699
BPGM	1093	669	Bisphosphoglycerate mutase deficiency	AD/AR	Pediatric		Hematologic	Hematologic		Phlebotomy has been reported as  beneficial in individuals with recessive disease involving severe loss of enzymatic function; Other reports indicate that RBC transfusions and splenectomy may be indicated in some individuals	14131784; 5885535; 11947623; 152321; 2542247; 1421379
BRAF	1097	673	Noonan syndrome; Cardiofaciocutaneous syndrome; LEOPARD syndrome 3	AD	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic;	Cardiovascular; Hematologic; Oncologic	Conditions may be frequently clinically recognized due to characteristic facial features as well as other manifestations	Surveillance and treatment related to  manifestations such as cardiac anomalies (which include pulmonic stenosis, hypertrophic cardiomyopathy, and arrhythmias) can be beneficial; The disorder can include bleeding diathesis,  and recognition and preventive measures (eg, in surgical situations) can be beneficial; Individuals with malignancies (eg, ALL) have been reported, and awareness of increased risk may be beneficial	16474404; 16439621; 17551924; 17483702; 19047498; 18456719; 18042262; 18413255; 19206169; 20301303; 20301365; 20523244; 21349766; 21495173 
BRAT1	21701	221927	Rigidity and multifocal seizure syndrome, lethal neonatal	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22279524
BRCA1	1100	672	Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to	AD	Adult		Oncologic	Oncologic	Mutations may also predispose to a number of other maligancies	Though the availability of empirical data is incomplete as applies to both screening strategies and prophylactic treatment, surveillance is based on the age of affected family members (for breast cancer, surveillance includes self-examination as well as regular clinical examinations, mammography, and MRI; for ovarian cancer, screening includes regular pelvic examination, transvaginal ultrasounds with Doppler, and CA-125 measurement; for prostate cancer, screening includes regular rectal examination and PSA measurement); Prophylactic mastectomy and/or oophorectomy, as well as chemoprevention (eg, with tamoxifen) are described; Treatment of breast and ovarian cancer follows standard guidelines (ie, that apply more generally), though, new targeted therapies are under investigation 	7894491; 7894493; 7545954; 9012404; 9450858; 10441598; 10885351; 12036267; 11133358; 11463017; 11463009; 12023992; 12023993; 12161607; 14569130; 12677558; 17233897; 17307836; 18413374; 18349832; 18762988; 19656774; 19190154; 20495085; 21531449; 22317870; 20216074; 22614657 
BRCA2	1101	675	Breast-ovarian cancer, familial, susceptibility to; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3; Fanconi anemia, complementation group D1; Wilms tumor; Medulloblastoma	AD/AR	Pediatric (Fanconi anemia, complementation group D1); Adult (Breast-ovarian cancer, familial, susceptibility to; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3; Wilms tumor; Medulloblastoma)		Allergy/Immunology/Infectious; Dermatologic; Hematologic; Neurologic; Oncologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Oncologic	Mutations may also predispose to a number of other malignancies	For hereditary breast and ovarian cancer, though the availability of empirical data is incomplete as applies to both screening strategies and prophylactic treatment, surveillance is based on the age of affected family members (for breast cancer, surveillance includes self-examination as well as regular clinical examinations, mammography, and MRI; for ovarian cancer, screening includes regular pelvic examination, transvaginal ultrasounds with Doppler, and CA-125 measurement; for prostate cancer, screening includes regular rectal examination and PSA measurement); Prophylactic mastectomy and/or oophorectomy, as well as chemoprevention (eg, with tamoxifen) are described; Treatment of breast and ovarian cancer follows standard guidelines (ie, that apply more generally), though, new targeted therapies are under investigation; There are little empiric data regarding other cancer types, though awareness may allow early diagnosis and treatment; For Fanconi anemia: Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count), and HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended;	8091231; 8524414; 7597059; 9140390; 10441598; 10807385; 12036267; 11133358; 12065746; 12097290; 12161607; 12023992; 12023993; 14569130; 12556369; 14670928; 15912495; 15948173; 15689453; 16825431; 18264087; 18349832; 18355772; 18413374; 19190154; 21118973; 21593217; 21531449; 20216074; 22614657; 23285130
BRIP1	20473	83990	Breast cancer; Fanconi anemia, complementation group J	AD/AR	Pediatric (Fanconi anemia, complementation group J); Adult (Breast  cancer)		Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Hematologic; Oncologic	Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	For Breast cancer, awareness may allow early surveillance, preventive measures, and early diagnosis and treatment of disease; For Fanconi anemia, specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended	11301010; 14630800; 14983014; 16116424; 16116423; 17033622; 21568838; 21964575; 22006311; 22441895; 23285130
BRWD3	17342	254065	Mental retardation, X-linked 93	XL	N/A	N/A	Craniofacial; Genitourinary; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7943039; 17668385; 19377476
BSCL2	15832	26580	Lipodystrophy, congenital generalized, type 2; Encephalopathy, progressive, with or without lipodystrophy	AR	Pediatric	Allelic with Neuropathy, distal hereditary motor, type V (AD); Charcot-Marie-Tooth disease type 2 (AD); Silver syndrome (AD); Silver spastic paraplegia syndrome (AD); Spastic paraplegia 17 (AD)	Cardiovascular; Endocrine; Neurologic	Cardiovascular; Endocrine		Dietary measures (eg, restriction of fat intake) and medications (eg, leptin)  may be beneficial; Individuals may have cardiomyopathy, and surveillance and early medical management may be beneficial	5964029; 10908191; 14602785; 12362029; 14981520; 15732094; 16427281; 17671040; 19396477; 19041432; 21126715; 20301391; 23142943; 23564749
BSG	1116	682	Blood group, OK	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	9130641
BSND	16512	7809	Bartter syndrome, type 4a; Sensorineural deafness with mild renal dysfunction 	AR	Pediatric		Audiologic/Otolaryngologic; Renal	Audiologic/Otolaryngologic; Renal		Individuals may have renal perturbations, (eg, including metabolic alkalosis and hypokalemia), for which treatment can be beneficial; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	11687798; 12574213; 19646679; 21158220; 21269598 
BTD	1122	686	Biotinidase deficiency	AR	Pediatric		Allergy/Immunology/Infectious; Biochemical; Dermatologic; Neurologic; Ophthalmologic	Biochemical		Individuals with severe biotinidase deficiency can present with a range of neurologic, visual, and dermatologic anomalies, which are typically not reversible after manifesting, and medical management (with oral biotin) is indicated and can prevent sequelae if instituted early; Raw eggs should be avoided due to resultant decreased biotin bioavailability	4103667; 917614; 88555; 99258; 7436398; 6790844; 6135889; 6137736; 6848914; 3930842; 3926500; 4000223; 4073853; 196050; 2502673; 2515386; 2109151; 1729884; 8283357; 7550325; 9396567; 9375914; 9654207; 15776412; 7550325; 11313766; 17382128; 21752405; 20301497; 21696988; 21907891; 22378278; 22241090 
BTK	1133	695	Agammaglobulinemia, X-linked; Agammaglobulinemia and isolated hormone deficiency; Hypogammaglobulinemia, X-linked	XL	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis, including gammaglobulins, sometimes with prophylactic antibiotics and early and aggressive treatment of infections may be beneficial; Live viral vaccines should be avoided; Recognition and treatment of growth hormone deficiency may be beneficial	13380950; 4578158; 3488506; 6783908; 8380905; 8013627; 7722175; 8982147; 9545398; 11445810; 12378199; 12217331; 12958074; 16159644; 16297664; 16377251; 19302039; 19651503; 18241230; 20301626 
BUB1B	1149	701	Mosaic variegated aneuploidy syndrome; Premature chromatid separation trait	AD/AR	Pediatric		Musculoskeletal; Neurologic; Oncologic; Ophthalmologic	Oncologic	The condition can involve a number of congenital anomalies	The disorder is frequently but not always clinically recognizable, and there is a high risk of malignancy, for which surveillance and early treatment may be beneficial; Affected women have been reported as having recurrent chromosomally abnormal conceptuses, and reproductive counseling as well as preconception planning may be beneficial	2935477; 3780318; 8225320; 9677059; 10429359; 9916837; 11169558; 11746029; 15475955; 15098246; 16411201; 21190457
C10ORF11	23405	83938	Albinism, oculocutaneous, type V	AR	N/A	N/A	Dermatologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23395477
C10ORF2	1160	56652	Mitochondrial DNA depletion syndrome 7 (hepatocerebral type); Perrault syndrome 5	AR	Pediatric	Allelic with Progressive external ophthalmoplegia, autosomal dominant, 3 (AD)	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Biochemical		Individuals may have biochemical manifestations, including fasting hypoglycemia responsive to glucose therapy	8133312; 7719341; 10522883; 11431692; 12210792; 16135556; 17921179; 17722119; 18775955; 18971204; 20479361; 20880070; 21519523; 21681116; 21689831; 22353293; 22928142; 23375728; 25355836
C12ORF57	29521	113246	Corpus callosum hypoplasia, recessive; Temtamy syndrome	AR	N/A	N/A	Craniofacial; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17632789; 21937992; 23453665; 23453666; 23633300; 24798461
C12ORF65	26784	91574	Combined oxidative phosphorylation deficiency 7; Spastic paraplegia 55, autosomal recessive 	AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3479531; 20598281; 23188110; 24198383
C15ORF41	26929	84529	Congenital dyserythropoietic anemia type Ib	AR	Pediatric		Hematologic; Musculoskeletal	Hematologic		Individuals have been described as manifesting with early childhood onset, severe anemia requiring treatment via RBC transfusion	9220189; 16643456; 16754775; 23716552
C19ORF12	25443	83636	Neurodegeneration with brain iron accumulation 4; Spastic Paraplegia 43	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21981780; 22508347; 23269600; 23447832; 23494994; 23521069; 23857908
C1QA	1241	712	C1q deficiency	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Renal	Allergy/Immunology/Infectious	Individuals are also prone to autoimmune disease (eg, glomerulonephritis, SLE)	While the majority of sequelae may involve autoimmune manifestations (for which treatment with FFP may be beneficial), some individuals have been described with frequent and/or severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	6445507; 6319055; 7594474; 8840296; 9225968; 10776791; 20560256; 22576477 
C1QB	1242	713	C1q deficiency	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Renal	Allergy/Immunology/Infectious	Individuals are also prone to glomerulonephritis and SLE	While the majority of sequelae may involve autoimmune manifestations (for which treatment with FFP may be beneficial), some individuals have been described with frequent and/or severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	6445507; 6319055; 2894352; 23651859
C1QC	1245	714	C1q deficiency	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Renal	Allergy/Immunology/Infectious	Individuals are also prone to glomerulonephritis and SLE	While the majority of sequelae may involve autoimmune manifestations (for which treatment with FFP may be beneficial), some individuals have been described with frequent and/or severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	6445507; 6319055; 8630118; 225968
C1QTNF5	14344	114902	Late-onset retinal degeneration	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12944416; 22277927;  23289492
C1S	1247	716	Complement component C1s deficiency	AR	Pediatric		Allergy/Immunology/Infectious; Renal	Allergy/Immunology/Infectious		Described individuals may suffer from conditions such as severe infections, for which prophylaxis and/or early and aggressive treatment of infection may be beneficial; Immunosuppression may be beneficial for autoimmune phenomena (such as lupus nephritis)	9856483; 9973493; 11390518; 19155518; 20191570
C2	1248	717	Complement component 2 deficiency	AR	Pediatric		Allergy/Immunology/Infectious; Renal	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial for infectious manifestations; Patients may also develop autoimmune manifestations, and treatment with immune modulators has been described	14446782; 4161820; 1124106; 2582254; 1542325; 1361318; 1577763; 8621452; 15643297; 16026838; 20417301; 20890976; 22842196 
C2CD3	24564	26005	Orofaciodigital syndrome XIV	AR	N/A	N/A	Cardiovascular; Craniofacial; Dental; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24997988
C2ORF71	34383	388939	Retinitis pigmentosa 54	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20398884; 20398886; 20811058; 21412943; 21792230
C3	1318	718	Complement component 3 deficiency, autosomal recessive; Hemolytic uremic syndrome, atypical, susceptibility to, 5	AR	Pediatric	Allelic with Macular degeneration, age-related (AD)	Allergy/Immunology/Infectious; Hematologic; Ophthalmologic;  Renal	Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic; Renal		Antiinfectious prophylaxisa and early and aggressive treatment of infections may be beneficial; In hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications)	4117597; 1976733; 1350678; 1575793; 15781264; 18796626; 19846853; 20807612; 20595690; 22410797 
C4A	1323	720	Blood group, Chido/Rodgers system	BG	Pediatric	Allelic with Complement component 4A deficiency (AR)	Allergy/Immunology/Infectious; Hematologic; Renal	Hematologic	In Complement component 4A deficiency, renal transplant has been described	Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	4190973; 6932037; 7451653; 2862466; 3260957; 2551816; 2295875; 2243578; 2289315; 2384609; 8473511; 7706484; 22387014
C4B	1324	721	Complement component 4B deficiency	AR	N/A	N/A	Allergy/Immunology/Infectious	General	Biallelic decificiency may include bacteremia and meningitis susceptibility	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4190973; 7451653; 2862466; 3501712; 3260957; 3265961; 2551816; 2384609; 1401055; 20580617; 22387014
C5	1331	727	 Eculizumab, poor response to; Complement component 5 deficiency	AD/AR	Pediatric		Craniofacial; Musculoskeletal; Neurologic	Allergy/Immunology/Infectious;  Pharmacogenomic		In Complement component 5 deficiency, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Recognition of  is important because effective therapy is available (eg, fresh plasma vs. banked blood); Heterozygous variants have been described as resulting in poor response to eculizumab	5411128; 4258194; 7730648; 21270745; 21635555; 22123893; 22668955; 23371790
C5ORF42	25801	65250	Joubert syndrome 17; Orofaciodigital syndrome VI	AR	N/A	N/A	Craniofacial; Genitourinary; Musculoskeletal; Neurologic	General	The condition may involve multi-systemic manifestations, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5816874; 20301500; 22425360; 23169490; 24178751
C6	1339	729	Complement component 6 deficiency	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious	Antiinfectious prophylaxis (including related to specific immunization strategies) and early and aggressive treatment of infections may be beneficial	Antiinfectious prophylaxis (including related to specific immunization) and early and aggressive treatment of infections may be beneficial	11344568; 11344569; 6835295; 8690922; 17257682; 17893986; 21270745; 22123893; 22288589; 22668955 
C7	1346	730	Complement component 7 deficiency	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis (including related to specific immunization strategies) and early and aggressive treatment of infections may be beneficial	3685247; 2792129; 8892662; 8871666; 17407100; 15328683; 21270745; 22123893; 20591074; 22206826 
C8A	1352	731	Complement component 8 deficiency, type I	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis (including related to specific immunization strategies) and early and aggressive treatment of infections may be beneficial	6822660; 6433145; 9759902; 21270745; 22123893  
C8B	1353	732	Complement component 8 deficiency, type II	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis (including related to specific immunization strategies) and early and aggressive treatment of infections may be beneficial	6822660; 8098723; 9476133; 21270745; 22123893
C8ORF37	27232	157657	Retinitis pigmentosa 64; Cone-rod dystrophy 16	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22177090
C9	1358	735	Complement component 9 deficiency	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious	In some individuals, there has been no evidence of "predicted" sequelae (eg, Neisseria infections)	Antiinfectious prophylaxis (including related to specific immunization) and early and aggressive treatment of infections may be beneficial	7430628; 2744767; 8747118; 9703418; 10083734; 12596049; 15943177; 21270745; 22123893; 22381107 
C9ORF72	28337	203228	Amyotrophic lateral sclerosis and/or frontotemporal dementia 1	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21944778; 21944779; 23551834; 23597494; 24027057
CA12	1371	771	Hyperchlorhidrosis, isolated	AR	Pediatric		Renal	Renal		In infancy, salt wasting can lead to severe hyponatremic dehydration/hyperkalemia, and precautionary measures (eg, sodium supplementation) can be beneficial	21035102; 21184099 
CA2	1373	760	Osteopetrosis, autosomal recessive 3, with renal tubular acidosis	AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Musculoskeletal; Renal		Identification and treatment of renal tubular acidosis may be beneficial; Awareness of multi-organ system complications of osteopetrosis may allow surveillance and prompt management	5041390; 7386510; 7312081; 3925334; 3081869; 2107079; 1928091; 1301935; 1542674; 8127074; 7627193; 8834238; 9143915; 12566520
CA4	1375	762	Retinitis pigmentosa 17	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7581389; 9385361; 15090652; 15563508; 17652713
CA5A	1377	763	Carbonic anhydrase VA deficiency	AR	Pediatric		Biochemical	Biochemical		Medical treatment (with carglumic acid) has been reported as resolving hyperammonemia in affected individuals	24530203
CA8	1382	767	Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19461874; 21937992
CABP2	1385	51475	Deafness, autosomal recessive 93	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	22981119; 21542834
CABP4	1386	57010	Night blindness, congenital stationary, type 2B	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16960802
CACNA1A	1388	773	Episodic ataxia, type 2; Migraine, familial hemiplegic 1	AD	Pediatric	Allelic with Spinocerebellar ataxia 6 (AD)	Neurologic	Neurologic; Pharmacogenomic		Medical treatment (eg, 4-aminopyridine, acetazolamide, as well as other standard migraine-related medications to treat migraines in disorders with migraines) may be effective; Vasoconstricting agents (due to risk of stroke) and cerebral angiograophy (due to risk of precipitation of attack) should be avoided	6684259; 3469025; 1575453; 7757080; 8898206; 14681882; 9311738; 9302278; 9259274; 9259275; 8734765 ; 9403486; 9345107; 8988170; 15210532; 9915947; 10668728; 11439943; 11673601; 12081723; 12056940; 12707077; 14681882; 14718690; 15136697; 15362569; 16186543; 15710862; 15747371; 17575281; 17142831; 18541804; 18685131; 20301562; 19633872; 21734179; 20837964
CACNA1C	1390	775	Brugada syndrome 3; Timothy syndrome	AD	Pediatric		Allergy/Immunology/Infectious; Cardiovascular; Musculoskeletal; Neurologic 	Allergy/Immunology/Infectious; Cardiovascular; Pharmacogenomic	In Timothy syndrome, features may be clinically recognizable, but individuals may be at risk  for lethal arrhythmias; Somatic mosaicism has been described in Timothy syndrome	For Brugada syndrome-related manifestations, surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial;  Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever; For immune deficiency (such as is described in some individuals with Timothy syndrome), preventive measures and monitoring and early and aggressive treatment of infections may be beneficial	1318983; 7572644; 15454078; 15863612; 17224476; 21910241; 20301690
CACNA1D	1391	776	Primary aldosteronism, seizures, and neurologic abnormalities; Sinoatrial node dysfunction and deafness	AD/AR	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Neurologic	Audiologic/Otolaryngologic; Cardiovascular; Endocrine		In Primary aldosteronism, seizures, and neurologic abnormalities, individuals may manifest with arrhythmias and other cardiac abnormalities, and awareness may allow prompt detection and treatment; Individuals may manifest with endocrine anomalies (eg, hypokalemia, hypoglycemia, hyperaldostorenemia), and awareness may allow early diagnosis and treatement, which has been described as benefitting some parameters; In Sinoatrial node dysfunction and deafness, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals may demonstrate evidence of dysrhythmias (eg, manifesting with bradycardia, with syncopal episodes associated with and without physical activity and stress described), and surveillance (eg, with EKG) may be beneficial in order to allow early medical management	21131953; 23913001
CACNA1F	1393	778	Aland Island eye disease; Cone-rod dystrophy, X-linked, 3; Night blindness, congenital stationary, X-linked, type 2A	XL	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14230113; 14213931; 9662400; 9662399; 11381068; 12111638; 12807962; 16505158; 17525176; 20001510; 20301423; 22194652; 22744390 
CACNA1S	1397	779	Malignant hyperthermia susceptibility 5; Thyrotoxic period paralysis, susceptibility 1; Hypokalemic periodic paralysis, type 1	AD	Pediatric		Cardiovascular; Endocrine; Musculoskeletal; Renal	Cardiovascular; Endocrine; Pharmacogenomic; Renal		In Malignant hyperthermia, early diagnosis, discontinuation of potent inhalation agents/succinylcholine, treatment of metabolic abnormalities, and administration of dantrolene sodium intravenously are essential to  treat acute MH; In Thyrotoxic periodic paralysis, treatment of hyperthyroidism results in resolution of paralysis; In Hypokalemic periodic paralysis, paralytic crises can be treated with potassium; Dietary (eg,  low sodium/carbohydrate) and medical (eg,  potassium, acetazolamide) therapy can be effective; Cardiac surveillance can be beneficial	1148686; 457125; 3855357; 3839536; 8004673; 7897626; 9199552; 11591859; 11353725; 15001631; 15534250; 18835861; 19118277; 20301512; 20301325; 22253645; 22094484; 22901280 
CACNA2D2	1400	9254	Early infantile epileptic encephalopathy, High voltage gated calcium channelopathy-related, autosomal recessive	AR	N/A	N/A	Neurologic	General	The pathogenicity of the reported variants has been described as unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23339110
CACNA2D4	20202	93589	Retinal cone dystrophy 4	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17033974
CACNB2	1402	783	Brugada syndrome 4	AD	Pediatric		Cardiovascular	Cardiovascular; Pharmacogenomic		Surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial;  Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever	17224476; 20301690; 22090166
CACNB4	1404	785	Episodic ataxia, type 5	AD	Pediatric	Allelic with Epilepsy, idiopathic generalized, susceptibility to (AD), which appears to be an incompletely penetrant condition, and for which optimal seizure control would be beneficial, but may not otherwise require specific interventions	Neurologic	Neurologic	Variants may modify seizure-related conditions due to mutations in other genes (eg, SCN1A)	Individuals may manifest with recurrent attacks of vertigo and ataxia, and treatment with acetazolamide has been reported as being effective	10762541; 16100538; 18755274 
CACNG2	1406	10369	Mental retardation, autosomal dominant 10	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21376300
CALM1	1442	801	Ventricular tachycardia, catecholaminergic polymorphic, 4; Recurrent cardiac arrest, infantile	AD	Pediatric		Cardiovascular; Neurologic	Cardiovascular		Individuals may present with severe cardiac manifestations, including arrhythmias, syncope, and sudden death, and surveillance, preventive measures (eg, including avoidance of dangerous or excacerbating factors), and treatment (eg, including medical treatment with beta-blockers or ICD placement, which have both been described as beneficial in affected individuals) may allow early and beneficial management	23040497; 23388215 
CALM2	1445	805	Recurrent cardiac arrest, infantile	AD	Pediatric		Cardiovascular; Neurologic	Cardiovascular		Individuals may suffer from neonatal-onset severe and potentially lethal arrhythmias, and awareness may allow preventive treatment (eg, with beta-blocking medications and ICD placement) and rapid medical response, which may potentially ameliorate morbidity and mortality	23388215
CALR3	20407	125972	Cardiomyopathy, familial hypertrophic, 19	AD	Pediatric		Cardiovascular	Cardiovascular		Surveillance (eg, including echocardiography) for manifestations can allow early diagnosis, preventive measures relating to disease sequelae, and prompt treatment, which may reduce morbidity and mortality	16199542; 17655857 
CAMTA1	18806	23261	Cerebellar ataxia, nonprogressive, with mental retardation	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22693284
CANT1	19721	124583	Desbuquois dysplasia 1	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	Ophthalmologic		As the condition can include glaucoma, appropriate surveillance may allow early detection and management	1080993; 1959544; 7977470; 14679586; 14679587; 15211652; 19853239; 20358610; 20425819; 20358597; 21037275; 21412251; 21654728; 22539336 
CAPN3	1480	825	Muscular dystrophy, limb-girdle, type 2A; Eosinophilic myositis	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7720071; 10069710; 10330340; 15694138; 16607617; 16971480; 18854869; 21204801; 22378277; 22622166; 22926650 
CARD11	16393	84433	Congenital B cell lymphocytosis; Immunodeficiency 11	AD/AR	Pediatric		Allergy/Immunology/Infectious; Oncologic	Allergy/Immunology/Infectious; Oncologic		For  Immunodeficiency 11, individuals may be prone to frequent infections, and prophylactic measures, as well as early and aggressive treatment of infections may be beneficial; For Congenital B cell lymphocytosis, individuals may be predisposed to B cell malignancy, and awareness may allow early recognition and management; HSCT has been described in Congenital B cell lymphocytosis	23374270; 23561803
CARD14	16446	79092	Psoriasis 2	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8178173; 15689454; 22521418
CARD9	16391	64170	Candidiasis, familial, 2	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals can have recurrent (and lethal) fungal infections, and surveillance, prophylaxis, and early treatment may be beneficial	19864672; 23335372; 24131138
CASK	1497	8573	Mental retardation and microcephaly with pontine and cerebellar hypoplasia; FG syndrome 4; Mental retardation, with or without nystagmus	XL	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Neurologic; Ophthalmologic	Audiologic/Otolaryngologic	The condition typically includes profound neurological impairment, though the severity can vary	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	12522552; 19165920; 19200522; 19377476; 20029458; 21735175; 21954287
CASP10	1500	843	Autoimmune lymphoproliferative syndrome, type IIA	AD	Pediatric		Allergy/Immunology/Infectious; Hematologic; Oncologic	Allergy/Immunology/Infectious; Oncologic	Variants may modify other related disorders	Lymphoproliferation can be suppressed with medications such as corticosteroids, cyclosporine, tacrolimus, sirolimus, and mycophenolate mofetil; BMT/HSCT the only curative treatment for ALPS, has to date mostly been reported in patients with severe clinical findings; Surveillance for manifestations of lymphoproliferation and autoimmunity, and specialized imaging studies to detect malignant transformation may be beneficial	10412980; 16537120; 16446975; 17999750; 20301287 
CASP8	1509	841	Caspase 8 defiency	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	12353035; 15459299; 19930184; 21447005
CASQ2	1513	845	Ventricular tachycardia, catecholaminergic, polymorphic, 2	AR	Pediatric		Cardiovascular	Cardiovascular		Individuals may present with sudden cardiac death (eg, in the setting of exercise or excited states), and the overall mortality in untreated individuals is high early in life, such that surveillance and preventive measures/medical management, including ICD treatment, may be helpful to help decrease morbidity (however, storms of ventricular tachycardia have been described as being treated but not terminated through ICD shocks, and did not degenerate to ventricular fibrillation)	11401939; 16908766; 22481011; 22650415 
CASR	1514	846	Hyperparathyroidism, neonatal; Hypocalcemia, autosomal dominant; Hypocalcemia, autosomal dominant, with Bartter syndrome; Hypocalciuric hypercalcemia, type I; Hyperparathyroidism, neonatal severe primary; Hypoparathyroidism, familial isolated; Hyperparathyroidism, familial primary 	AD/AR	Pediatric	Allelic with Idiopathic generalized epilepsy 8 (AD)	Endocrine; Musculoskeletal; Neurologic; Renal	Endocrine; Renal		Sequelae, which can be severe in some individuals with hyperparathyrodism, can include seizures, and treatment (eg, with Vitamin D and calcium) can be effective at preventing morbidity; Early diagnosis of NSPHT is critical as the disorder can neurologically devastating or lethal without parathyroidectomy; In some forms of hypoparathyroidism, treatment of hypocalcemia with vitamin D/ vitamin D metabolites can cause hypercalciuria and resultant renal impairment, and PTH injections or diuretic treatment may be effective; In familial hypocalciuric hypercalcemia, accurate diagnosis may be important in order to decrease the use of unhelpful therapies	18887540; 14089114; 5013415; 830920; 619857; 7054696; 3966479; 7916660; 7874174; 7673400; 7726161; 8132750; 8675635; 8733126; 8813042; 9109436; 9011580; 9253358; 9642634; 9661634; 11013439; 10770217; 11134112; 11701698; 11293637; 12107202; 12241879; 12915654; 15579740; 15241791; 16608894; 17698911; 17018660; 18328986; 18756473; 21986511; 19250271; 22315359 
CAT	1516	847	Acatalasemia	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious; Pharmacogenomic		Individuals may be prone to manifestations such as oral ulcers and gangrene, and prompt treatment of infections may be beneficial; Pharmacogenomically, variants may be related to adverse reactions with treatment with medications such as uric acid oxidase 	12991731; 13904105; 2308162; 1999334; 1591863; 1551654; 8673475; 11117918; 11001624; 11197178; 11603354; 11500062; 15771551; 15800961; 17729111 
CAV1	1527	857	Lipodystrophy, congenital generalized, type 3; Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome	AD/AR	Pediatric	Allelic with Pulmonary artery hypertension, autosomal dominant (AD)	Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic	Cardiovascular; Endocrine; Gastrointestinal		Dietary measures and medications may be beneficial; Surveillance for manifestations, including diabetes and abnormal lipid balance may allow early diagnosis and treatment	15028826; 18211975; 18237401; 21865368; 22474227
CAV3	1529	859	Cardiomyopathy, familial hypertrophic; Long QT syndrome 9; Creatine phosphokinase, elevated serum	AD/Digenic	Pediatric	Allelic with Muscular dystrophy, limb-girdle, type IC (AD); Myopathy, distal, Tateyama type (AD); Rippling muscle disease (AD/AR)	Cardiovascular; Musculoskeletal	Cardiovascular; Pharmacogenomic	Conditions may involve digenic inheritance	Preventive measures and medical management may be helpful to help decrease morbidity related to cardiovascular manifestations; In individuals with isolated CK elevation, precautions should be taken during surgical/anesthetic procedures and anesthesia due to malignant hyperthermia risk	2705900; 9536092; 9537420; 10220144; 10227634; 10746614; 11431690; 11251997; 11805270; 12939441; 12666119; 14672715; 15668980; 16247063; 17060380; 17275750; 20229577; 20301308; 20301559; 20809527; 22245016; 22581547 
CBL	1541	867	Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia	AD	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic	Cardiovascular; Oncologic		Though the condition may be recognizable, surveillance/early treatment of tumors may reduce morbidity; The condition may also include cardiac anomalies and dysrhythmias, and appropriate surveillance and care may be beneficial	20694012; 20543203 
CBS	1550	875	Homocystinuria due to cystathionine beta-synthase deficiency	AR	Pediatric		Biochemical; Cardiovascular; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	Biochemical; Hematologic; Ophthalmologic; Pharmacogenomic		Some individuals may respond to medical therapy (eg, pyridoxine, folic acid, betaine, hydroxycobalamin) and/or dietary therapy (eg, methionine restriction); Surveillance for and prompt treatment of thromboembolic complications can be beneficial; Awareness of ocular complications (eg, ectopia lentis) can allow prompt and appropriate treatment; Certain agents (eg, oral contraceptives) should be avoided, and special considerations may need to be taken into account if surgery is required	14018926; 13960563; 5658872; 5658866; 7325153; 6711564; 4033699; 934499; 3591841; 2116556; 7506602; 7967489; 7762555; 8554066; 8592550; 8940271; 9427154; 9787359; 10364517; 10338090; 10564686; 10780316; 11343305; 11596648; 12124992; 12227460; 12007221; 12118525; 11857551; 12552044; 14635102; 16205833; 17686644; 20142522; 20301697; 18280597; 19370759; 19819175; 21520339; 21308989; 21240075; 20567906; 21626167; 24168815; 24169224
CBX2	1552	84733	46,XY sex reversal 5	AR	N/A	N/A	Endocrine; Genitourinary	General		There was no evidence for dysgenetic gonads in the reported patient; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19361780
CC2D1A	30237	54862	Mental retardation, autosomal recessive 3	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16033914; 17149387
CC2D2A	29253	57545	Joubert syndrome 9; Meckel syndrome 6; COACH syndrome	AR	N/A	N/A	Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary; Renal	General	The condition can involve multiple congenital anomalies; Digenic inheritance has been reported	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18950740; 18387594; 18513680; 20301500; 20671153; 22246503; 22241855 
CCBE1	29426	147372	Hennekam lymphangiectasia-lymphedema syndrome	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Neurologic; Renal	Allergy/Immunology/Infectious; Endocrine; Gastrointestinal		The condition can include manifestations such as protein-losing enteropathy (which may be refractory), as well as features for which treatment can be beneficial, such as infectious sequelae, for which early and aggressive treatment may be beneficial; Individuals have been described with endocrine manifestations such as hypothyroidism and growth hormone deficiency, and awareness may allow prompt recognition and treatment	2624276; 1897580; 8465855; 7645602; 10925377; 12124738; 12376947; 14564208; 12794699; 19935664; 19911200; 22239599 
CCDC103	32700	388389	Ciliary dyskinesia, primary, 17	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	19720631; 20301301; 22581229
CCDC114	26560	93233	Ciliary dyskinesia, primary, 20	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	23261302; 23261303 
CCDC137	33451	339230	Schizophrenia	AD	N/A	N/A	Neurologic	General		Evidence or clinical applicability unclear	21743468
CCDC151	28303	115948	Ciliary dyskinesia, primary,30	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Musculoskeletal; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	25192045; 25224326
CCDC28B	28163	79140	Bardet-Biedl syndrome, modifier of	AD	N/A	N/A	General	General		Variants are described as related to modifying alleles, with little evidence that the variant would cause disease alone	12677556; 16327777; 22773737 
CCDC39	25244	339829	Ciliary dyskinesia, primary, 14	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	20301301; 21131972
CCDC40	26090	55036	Ciliary dyskinesia, primary, 15	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	20301301; 21131974
CCDC50	18111	152137	Deafness, autosomal dominant 44	AD	N/A	N/A	Audiologic/Otolaryngologic	General	Hearing loss has been reported to occur in the first decade (6-10 years)	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12483295; 17503326
CCDC8	25367	83987	Three M syndrome 3	AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21737058
CCDC88C	19967	440193	Spinocerebellar ataxia 40	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	25062847
CCM2	21708	83605	Cerebral cavernous malformations 2	AD	Pediatric		Cardiovascular; Neurologic	Cardiovascular; Neurologic; Pharmacogenomic		Surveillance measures (eg, spinal cord MRI, annual brain gradient echo or susceptibility-weighted imaging) has been advocated; Agents that increase risk of hemorrhage should be avoided (eg, aspirin, NSAIDs, heparin, warfarin). 	14624391; 17211633; 17160895; 18060436; 18779516; 19088123; 21543988; 20301470 
CCND2	1583	894	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24705253
CCNO	18576	10309	Ciliary dyskinesia, primary 29	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Genitourinary; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary	24747639; 24824133
CCT5	1618	22948	Neuropathy, hereditary sensory, with spastic paraplegia	AR	N/A	N/A	Neurologic	General	Among other neurologic features, individuals can demonstrate insensitivity to pain, which can result in injuries and infections	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16399879
CD151	1630	977	Raph blood group	BG	Pediatric	Allelic with Nephropathy with pretibial epidermolysis bullosa and deafness (AR)	Audiologic/Otolaryngologic; Dermatologic; Hematologic; Renal	Hematologic	Individuals with Nephropathy with pretibial epidermolysis bullosa and deafness may manifest with deafness, but it is described as typically postlingual	Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	3604155; 3238950; 3412548; 15265795; 18522704 
CD19	1633	930	Immunodeficiency, common variable 3	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Indidivuals may demonstrated increased susceptibility to infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	16672701
CD207	17935	50489	 Birbeck granule deficiency	AD	N/A	N/A	General	General		The condition may not involve clinical relevance	7798619; 15816828
CD247	1677	919	Immunodeficiency due to defect in CD3-Zeta	AR	Pediatric		Allergy/Immunology/Infectious; Gastrointestinal	Allergy/Immunology/Infectious		Individuals may present with a variety of infectious manifestations, including oral, pulmonary, and skin infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; The use of G-CSF has been reported, as has BMT	3262828; 16672702
CD27	11922	939	Lymphoproliferative syndrome 2	AR	Pediatric		Allergy/Immunology/Infectious; Hematologic; Oncologic	Allergy/Immunology/Infectious; Hematologic; Oncologic	HSCT has been described	The condition can involve childhood-onset immunodeficiency, and prophylactic measures, treatment, and prompt and aggressive treatment of infections may be beneficial; Individuals may manifest with hemophagocytic lymphohistiocytosis syndrome , and awareness can allow efficient management, but stem cell transplant may be indicated in such instances; Additional malignancies have been described, and awareness may allow recognition and treatment	22197273; 22365582; 22801960
CD2AP	14258	23607	Glomerulosclerosis, focal segmental, 3	AR	N/A	N/A	Renal	General	Renal transplant has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17713465
CD320	16692	51293	Methylmalonic aciduria due to transcobalamin receptor defect	AR	Pediatric		Biochemical	Biochemical	Treatment efficacy is unclear	Treatment with IM vitamin B12 has shown to positively affect laboratory parameters, but long-term clinical sequelae are unclear	20524213
CD36	1663	948	Platelet glycoprotein IV deficiency	AR	Pediatric		Hematologic	Hematologic		Platelet glycoprotein IV deficiency has been reported with refractoriness to HLA-matched platelet transfusion, and may act as a susceptibility factor for hypertrophic cardiomyopathy and other cardiovascular-related parameters	2617957; 10946357; 11247555; 15973412; 17668374; 17412877
CD3D	1673	915	Immunodeficiency 19	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals have been described with severe combined immunodeficiency, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported	14602880; 15546002
CD3E	1674	916	Immunodeficiency 18	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals have been described with severe combined immunodeficiency, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	8490660; 15546002
CD3G	1675	917	Immunodeficiency 17	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	1709425; 1635567
CD4	1678	920	OKT4 epitope deficiency	AD	N/A	N/A	General	General		There is weak or mixed evidence that the condition has an adverse health effect	6790623; 6209207; 6199335; 6199366; 6229573; 6208600; 1708753; 1961196; 7534484; 7541811; 7689618
CD40	11919	958	Immunodeficiency with Hyper-IgM, type 3	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial;  BMT has been reported	11675497; 12915844; 12584544; 17502893; 20301576
CD40LG	11935	959	Immunodeficiency, with hyper-IgM, type 1	XL	Pediatric		Allergy/Immunology/Infectious; Hematologic; Oncologic	Allergy/Immunology/Infectious; Oncologic		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals have been described as being at increased risk of malignancy, and awareness may allow early detection and management; BMT has been reported	7679801; 7678782; 7542361; 9255191; 10228294; 10931436; 10655530; 17296845; 20301576;  23010537; 22322937
CD44	1681	960	Blood group, Indian	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	1146277; 8636151
CD46	6953	4179	Hemolytic uremic syndrome, atypical, susceptibility to, 2	AD/AR	Pediatric		Hematologic; Renal	Hematologic; Pharmacogenomic; Renal	Digenic inheritance (with CFH) has been reported	In hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications), though treatment with plasma infusion was not reported to result in improved disease resolution in individuals with MCP mutations	14615110; 14566051; 15661753; 16621965; 16762990; 16386793; 17617869; 16882452; 20595690; 20301541 
CD55	2665	1604	Blood group, Cromer system	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	7519480; 8837357; 9427725; 21214297
CD59	1689	966	CD59 deficiency	AR	Pediatric		Hematologic	Hematologic		Surveillance to allow early diagnosis and treatment of manifestations including hemolytic anemia, as well as thrombotic risk, may be beneficial	1691667; 1699124; 1382994; 21707954; 23149847 
CD79A	1698	973	Agammaglobulinemia 3	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	10525050; 11920841
CD79B	1699	974	Agammaglobulinemia 6	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	17675462; 17709424
CD81	1701	975	Immunodeficiency, common variable, 6	AR	Pediatric		Allergy/Immunology/Infectious; Renal	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	20237408
CD8A	1706	925	CD8 deficiency, familial	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious	Asymptomatic individuals have been described	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	11435463; 17658607 
CD96	16892	10225	C syndrome( Opitz Trigonocephaly syndrome)	AD	N/A	N/A	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7258228; 3981579; 2260586; 10405439; 16835930; 16528754; 17847009
CDAN1	1713	146059	Anemia, dyserythropoietic  congenital, type Ia	AR	Pediatric		Cardiovascular; Hematologic; Musculoskeletal; Renal	Hematologic		Individuals may require RBC transfusions in the neonatal period; Medical therapy (eg, with alpha-interferon) may be beneficial; Iron overload is common	718245; 476312; 3096054; 2757972; 2124499; 7725852; 10971401; 10753260; 12434312; 16098079; 16141353; 18824595; 21378561; 21364188; 22504250 
CDC6	1744	990	Meier-Gorlin syndrome 5	AR	N/A	N/A	Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11477602; 21358632; 22333897
CDC73	16783	79577	Hyperparathyroidism, familial isolated; Hyperparathyroidism-jaw tumor syndrome; Carcinoma, parathyroid	AD	Pediatric		Endocrine; Oncologic; Renal	Endocrine; Oncologic		Parathyroidectomy (or medical treatment in individuals unable to undergo parathyroidectomy)  may be necessary to normalize calcium levels, and parathyroid adenomas may recur; Surveillance and early diagnosis/treatment of specific manifestations, including jaw tumor recurrence, parathyroid carcinoma, and renal neoplasms is indicated	11157996; 3592449; 12434154; 14585940; 14715834; 14985403; 15531515; 15606373; 16720667; 17639062; 17666472; 21361849; 20301744; 22187299; 23652676; 23757631
CDH1	1748	999	CDH1-related cancer	AD	Adult		Craniofacial; Oncologic	Oncologic	Variants may also be involved in other malignancies (eg, prostate cancer) either as minor or major risk factors; Variants have also been implicated in the development of facial clefting	Surveillance and prophlyactic measures (which may include prophylactic gastrectomy) may allow early diagnosis and treatment (though there is controversy regarding the efficacy of prophlyaxis and surveillance measures), which may potentially be beneficial in the reduction of morbidity and mortality	9751616; 9537325; 10072428; 10477433; 10319582; 11443625; 11968084; 11968083; 12588804; 15235021; 14961571; 16189707; 17660459; 19168852; 20301318; 22020549; 23124477; 23197654; 24037103
CDH15	1754	1013	Mental retardation, autosomal dominant 3	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19012874
CDH23	13733	64072	Deafness, autosomal recessive 12; Usher syndrome, type 1D; Usher syndrome, type 1D /F digenic	AR/Digenic	Pediatric		Audiologic/Otolaryngologic; Ophthalmologic	Audiologic/Otolaryngologic	Inheritance can be digenic, involving PCDH15	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	11138009; 11090341; 11138008; 15537665; 17850630
CDH3	1762	1001	Hypotrichosis, congenital, with juvenile macular dystrophy; Ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome	AR	N/A	N/A	Dermatologic; Musculoskeletal; Ophthalmologic	General	Heterozygotes may display subtle effects	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13372143; 10420194; 11544476; 12445216; 15805154; 20140736; 22140374; 22348569; 23143461 
CDHR1	14550	92211	Cone-rod dystrophy 15; Retinitis pigmentosa 65	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20805371
CDK4	1773	1019	Melanoma, cutaneous malignant, susceptibility to, 3	AD	Adult		Dermatologic; Oncologic	Dermatologic; Oncologic		Surveillance for melanoma in at-risk individuals (eg, with regular self-examination and clinical examination) may allow early detection and treatment, which may decrease morbidity and mortality	7652577; 8528263; 9425228; 15880589; 21801156; 23384855; 23546221
CDK5RAP2	18672	55755	Microcephaly, primary autosomal recessive, 3	AR	Pediatric		Audiologic/Otolaryngologic; Neurologic	Audiologic/Otolaryngologic		The condition can involve congenital hearing impairment, and early recognition and treatment may improve outcomes, including speech and language development	10677332; 15793586; 17764569; 22887808; 23726037; 23995685
CDK6	1777	1021	Microcephaly 12, primary, autosomal recessive	AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23918663
CDKL5	11411	6792	Epileptic encephalopathy, early infantile, 2; Rett syndrome, atypical; Angelman-like syndrome	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15499549; 15492925; 15689447; 18266744; 18809835; 18063413; 17993579; 19793311; 19241098; 19396824; 20602487; 21765152; 21770923; 21802232; 22264704; 22430159; 22521361; 22670135; 22678952; 22867051; 23064044 
CDKN1B	1785	1027	Multiple endocrine neoplasia, type IV	AD	Pediatric		Endocrine; Oncologic	Endocrine; Oncologic		Surveillance and risk awareness may allow prompt detection and treatment of associated neoplasms (in affected individuals, these have been reported as including primary hyperparathyroidism likely due to underlying neoplasm, pituitary adenoma, and renal angiomyolipoma), which may decrease associated morbidity and mortality	17030811; 20507346; 20824794; 21289244; 22129891 
CDKN1C	1786	1028	IMAGE syndrome; Beckwith-Wiedemann syndrome	AD	Pediatric	Allelic with Russell Silver syndrome (AD), which involves imprinting/maternal inheritance	Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Renal	Endocrine; Oncologic	The conditions may involve multiple malformations	While IMAGe syndrome may have a number of recognizable features, recognition may allow preventive/treatment measures related to adrenal insufficiency; In Beckwith-Wiedemann syndrome, surveillance and early detection of and treatment for malignancy may decrease morbidity and mortality; Recognition and surveillance for and treatment of neonatal hypoglycemia can be beneficial	8841187; 10424811; 11181570; 11751681; 12439823; 15769992; 15999116; 15887271; 16835919; 18668518; 19302842; 20503313; 20301568; 22585446; 22634751; 24065356
CDKN2A	1787	1029	Melanoma, familial; Melanoma-pancreatic cancer syndrome	AD	Pediatric		Dermatologic; Oncologic	Dermatologic; Oncologic	Other tumor types have been reported	Surveillance and diagnosis of malignancies (including melanoma and pancreatic cancer) may allow early diagnosis and treatment, potentially improving outcomes	7987387; 8153634; 7987388; 7666917; 7666916; 8653684; 9328469; 9699728; 9516223; 9603434; 9425228; 9916806; 10874641; 10956390; 1579459; 11506491; 11726555; 12019208; 11815963; 11807902; 12556369; 12700603; 15577313; 16822996; 17492760; 18178632; 20132244; 20653773; 21895773; 21325014; 21150883; 21801156; 20574843; 21570156; 21570154; 21625824; 22368299; 21614589; 22636603
CDON	17104	50937	Holoprosencephaly 11	AD	N/A	N/A	Craniofacial; Endocrine; Neurologic; Ophthalmologic	General	Individuals with holoprosencephaly  may demonstrate endocrine anomalies, including diabetes insipidus	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21802063
CDSN	1802	1041	Hypotrichosis 2; Peeling skin syndrome 1	AD/AR	N/A	N/A	Allergy/Immunology/Infectious; Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3652491; 10793007; 12754508; 20691404; 21191406; 21777220; 22146835 
CDT1	24576	81620	Meier-Gorlin syndrome 4	AR	N/A	N/A	Craniofacial; Endocrine; Musculoskeletal; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11477602; 11992493; 21358631
CEACAM16	31948	388551	Deafness, autosomal dominant 4B	AD	N/A	N/A	Audiologic/Otolaryngologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7655461; 21368133
CEBPA	1833	1050	Acute myeloid leukemia, familial	AD	Pediatric		Oncologic	Oncologic		Surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of malignancy, which may reduce morbidity and mortality	15575056; 15902292; 18768433; 18946494; 20963938; 22066712; 23716546
CEBPE	1836	1053	Specific granule deficiency	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals have severe immunocompromise, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	10359588; 11313242
CECR1	1839	51816	Polyarteritis nodosa, childhood-onset (ADA2 deficiency); Sneddon syndrome	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Among other manifestations, individuals have been described as presenting with hypogammaglobulinemia, as well as recurrent bacterial and viral infections, and immunosuppressive treatment has been described as beneficial, though other manifestations have been described as recalcitrant to these types of therapies; Medical management (eg, with TNF inhibitor) has been described as beneficial.	12804991; 24552284; 24552285; 25075844; 25075847
CEL	1848	1056	Maturity-onset diabetes of the young, type 8	AD	Pediatric		Endocrine; Gastrointestinal	Endocrine; Gastrointestinal		In addition to endocrine manifestations (diabetes mellitus), recognition and specific treatment for exocrine dysfunction may be beneficial	16369531; 18544793; 17989309; 19760265; 21784842; 21521318 
CENPE	1856	1062	Microcephaly 13, primary, autosomal recessive	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24748105
CENPJ	17272	55835	Seckel syndrome 4; Microcephaly, primary autosomal recessive, 6	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12843329; 15793586; 16900296; 20522431; 20978018; 21668957; 22775483 
CEP135	29086	9662	Microcephaly 8, primary, autosomal recessive	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22521416
CEP152	29298	22995	Seckel syndrome 5; Microcephaly 9, primary, autosomal recessive	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20598275; 21131973
CEP164	29182	22897	Nephronophthisis 15	AR	N/A	N/A	Gastrointestinal; Neurologic; Ophthalmologic; Pulmonary; Renal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22863007
CEP19	28209	84984	Morbid obesity and spermatogenic failure	AR	N/A	N/A	Endocrine; Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24268657
CEP290	29021	80184	Leber congenital amaurosis 10; Meckel syndrome 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14	AR	N/A	N/A	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary; Renal	General	The condition frequently involves multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16909394; 16682973; 16682970; 17564974; 17564967; 17554762; 17617513; 17898177; 17705300; 18327255; 20301537; 20690115; 20805370
CEP41	12370	95681	Joubert syndrome 15	AR/Digenic 	N/A	N/A	Gastrointestinal; Neurologic; Ophthalmologic; Pulmonary; Renal	General	The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial;  Digenic inheritance (with KIF7) has been reported	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20301500; 22246503
CEP57	30794	9702	Mosaic variegated aneuploidy syndrome 2	AR	Pediatric		Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Pulmonary	Endocrine	The condition can involve multiple congenital anomalies	Individuals have been described as manifesting with hypothyroidism (among other features), and medical replacement therapy may be beneficial	12116237; 18548531; 21552266; 24259107
CEP63	25815	80254	Seckel syndrome 6	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21983783
CEP83	17966	51134	Nephronophthisis 18	AR	N/A	N/A	Gastrointestinal; Neurologic; Ophthalmologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24882706
CERKL	21699	375298	Retinitis pigmentosa 26	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14681825
CERS3	23752	204219	Ichthyosis, congenital, autosomal recessive 9	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23549421; 23754960
CES1	1863	1066	Carboxylesterase 1 deficiency	AR	N/A	N/A	Biochemical	Pharmacogenomic		Selection and dosing of certain medications may be affected by the presence of variants	18485328
CETP	1869	1071	Hyperalphalipoproteinemia 1	AD/AR	N/A	N/A	Cardiovascular	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6738363; 3937535; 3867663; 2215607; 8675707; 12080388; 12499392; 15840744; 16049032; 17952847; 18354102; 19060911; 19428034; 20686565; 21354572; 21488146; 22122993; 22339301 
CFAP53	26530	220136	Heterotaxy, visceral, 6, autosomal recessive	AR	N/A	N/A	Cardiovascular; Gastrointestinal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22577226
CFAP57	26485	149465	van der Woude syndrome 2	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11781685; 21574244
CFB	1037	629	Hemolytic uremic syndrome, atypical; Complement factor B deficiency	AD/AR	Pediatric		Allergy/Immunology/Infectious; Hematologic; Renal	Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic; Renal		In hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications); In Complement factor B deficiency, individuals may manifest with severe and recurrent infections due to encapsulated bacteria, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	6903190; 6898304; 7452889; 16518403; 16936732; 17182750; 20301541; 24152280
CFC1	18292	55997	Transposition of the great arteries, dextro-looped 2; Double-outlet right ventricle; Heterotaxy, visceral, 2, autosomal	AD	N/A	N/A	Cardiovascular; Gastrointestinal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11062482; 11562933; 11799476; 18538293 
CFD	2771	1675	Complement factor D deficiency	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may manifest with increased susceptibility to bacterial infections (especially Neisseria), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	11457876; 16527897
CFH	4883	3075	Hemolytic uremic syndrome, atypical; Complement factor H deficiency	AD/AR	Pediatric	Allelic with Basal laminar drusen (AR)	Allergy/Immunology/Infectious; Hematologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic; Renal		In hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications); In Complement factor H deficiency, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	646435; 6461667; 2950269; 2966809; 7742208; 9312129; 2966809; 9811382; 9848786; 9551389; 10577907; 10975323; 10762557; 0803850; 11170895; 14583443; 12697737;  14978182; 14583443; 16299065; 16621965; 16612335; 17018561; 18268093; 21784901 
CFHR1	4888	3078	Hemolytic-uremic syndrome, atypical, susceptibility to	AD/AR/Digenic	Pediatric		Hematologic; Renal	Hematologic; Pharmacogenomic; Renal		Deletions related to hemolytic-uremic syndrome involve a contiguous deletion with CFHR3 or CFHR4; In hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications)	98489; 17367211; 18006700; 19435718; 20301541 
CFHR3	16980	10878	Hemolytic-uremic syndrome, atypical, susceptibility to	AD/AR/Digenic	Pediatric		Hematologic; Renal	Hematologic; Pharmacogenomic; Renal		Deletions related to hemolytic-uremic syndrome involve a contiguous deletion with CFHR1; In hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications)	16998489; 17367211; 18006700; 20694013; 20301541 
CFHR4	16979	10877	Hemolytic-uremic syndrome, atypical, susceptibility to	AD/AR/Digenic	Pediatric		Hematologic; Renal	Hematologic; Pharmacogenomic; Renal		Deletions related to hemolytic-uremic syndrome involve a contiguous deletion with CFHR1; In hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications)	19861685; 20301541 
CFI	5394	3426	Hemolytic uremic syndrome, atypical; Complement factor I deficiency	AD/AR	Pediatric		Allergy/Immunology/Infectious; Hematologic; Renal	Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic; Renal		In Hemolytic-uremic syndrome, atypical, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy, eculizumab), as well as decision to perform renal transplant, may be dictated by genetic diagnosis (though renal transplant has been described as not uniformly successful), and certain agents/precipitating factors should be avoided (eg, certain medications); In Complement factor I deficiency, antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial; Medical considerations relevant for Hemolytic uremic syndrome (caused by mutations in the same gene) may also be important for individuals diagnosed with Complement factor I deficiency	4188976; 4097977; 4507613; 849647; 7922290; 8613545; 15173250; 16412054; 16175037; 16621965; 16386793; 22903728 
CFL2	1875	1073	Nemaline myopathy 7	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17160903
CFP	8864	5199	Properdin deficiency, X-linked	XL	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals are especially susceptible to Neisseria infections, warranting infectious prophylaxis and early and aggressive treatment of infections	8530058; 8871668; 10909851; 22229731 
CFTR	1884	1080	Cystic fibrosis	AR	Pediatric	Allelic with Congenital bilateral absence of the vas deferens (AR)	Allergy/Immunology/Infectious; Endocrine; Gastrointestinal; Genitourinary; Pulmonary	Allergy/Immunology/Infectious; Endocrine; Gastrointestinal; Pulmonary		Early and aggressive multisystem management of pulmonary (with attention to infectious risks), pancreatic, and other manifestations can reduce morbidity and mortality; In the instance of specific mutations, targeted therapy (eg, ivacaftor) has been described as beneficial	5657013; 2296270; 1870650; 1284639; 1359500; 7678316; 7680769; 7739684; 7529962; 7539210; 9003498; 9395429;  9113931; 9150159; 9550361; 18685558; 9725921; 11134427; 12768409; 15948195; 17018651; 16778595; 17202412; 7413420; 18685558; 21083385; 21184098; 22047557; 22383668; 22942289; 23590265; 23616732; 23616952; 23757359; 23952705; 24004658; 24039402
CHAT	1912	1103	Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency; Myasthenic syndrome, congenital, associated with episodic apnea	AR	Pediatric		Musculoskeletal; Neurologic	Musculoskeletal; Neurologic; Pharmacogenomic		Prophylactic medications (anticholinesterase therapy) in order to prevent apneic episodes/sudden respiratory insufficiency secondary to fever/infections can be effective; Most individuals benefit from AChE inhibitors and/or potassium channel blockers , though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes. Some individuals with SCCMS are treated with quinidine, which has some major side effects and may be detrimental in individuals with AChR deficiency; In severely affected individuals, diagnosis may be difficult due to the presence of  failure to thrive, apneic episodes, and aspiration; Certain medications affecting neuromuscular transmission should be avoided	11172068; 12756141; 20301347
CHCHD10	15559	400916	Frontotemporal dementia and/or amyotrophic lateral sclerosis 2	AD	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24934289
CHD2	1917	1106	Epileptic encephalopathy, childhood-onset	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23020937
CHD4	1919	1108	Schizophrenia	AD	N/A	N/A	Neurologic	General		Evidence or clinical applicability unclear	21743468
CHD7	20626	55636	CHARGE syndrome; Isolated gonadotropin-releasing hormone deficiency	AD	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Musculoskeletal; Neurologic; Renal; Genitourinary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Renal; Genitourinary		In CHARGE syndrome, awareness of the potential for cardiovascular, renal, and genitourinary manifestations may allow surveillance and prompt treatment, and awareness of the risk of infections (T-cell abnormalities have been described in some individuals) may benefit efficient treatment of infectious sequelae; Awareness of the risk of hearing impairment may allow prompt detection and treatment aimed at speech and language development; In Isolated gonadotropin-releasing hormone deficiency, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to male fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required; Awareness of the risk of hearing impairment may allow prompt detection and treatment aimed at speech and language development	15300250; 16155193; 16400610; 17661815; 7334995; 17937444; 17684005; 18241060; 18074359; 18834967; 18978652; 18445044; 9375527; 19021638; 20301509; 22724017
CHD8	20153	57680	Autism, susceptibility to 18	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21572417; 22495306; 22495309; 22495311; 22521361; 23160955; 24998929
CHEK2	16627	11200	Li-Fraumeni syndrome 2	AD/AR	Adult		Oncologic	Oncologic	Variants may be associated with susceptibility to a number of different cancer types 	Surveillance for neoplasms (eg, breast cancer screening with MRI) may allow preventive measures (eg, with tamoxifen chemoprevention in the case of breast cancer) and early treatment, resulting in improved outcome of malignancies	10617473; 11719428; 11479205; 11967536; 12094328; 12533788; 12690581;  15122511; 15492928; 15087378; 15466005; 15239132; 16257342; 12690581; 17085682; 16551709; 16835864; 18178638; 22058428; 22114986; 21787115; 22006311; 21807500; 22201027; 22072393; 21956126 
CHIT1	1936	1118	Chitotriosidase deficiency	AR	N/A	N/A	Biochemical	General		Variants may have implications for monitoring (including related to therapy) in Gaucher disease; Testing relevant to Gaucher disease, if necessary, would be tested as part of care	8132768; 9748235; 16972172; 17464953; 17693102; 15900564; 15528158; 22959626 
CHKB	1938	1120	Muscular dystrophy, congenital, megaconial type	AR	Pediatric		Cardiovascular; Dermatologic; Musculoskeletal; Neurologic	Cardiovascular		The condition can include cardiac sequelae (eg, cardiomyopathy and arrhythmias), and surveillance (eg, with echocardiogram and electrocardiogram) can allow potentially beneficial medical interventions	9427222; 21665002; 22782513 
CHM	1940	1121	Choiroideremia	XL	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2886237; 1302003; 1598901; 8477262; 7981671; 12827496; 19764077; 20301511; 22965595; 24913019
CHMP1A	8740	5119	Pontocerebellar hypoplasia, type 8	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23023333
CHMP2B	24537	25978	Amyotrophic lateral sclerosis, CHMP2B-related; Dementia, familial, nonspecific; Frontotemporal dementia, chromosome 3-linked 	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8541850; 12451202; 16041373; 16954699; 16807408; 17956895; 20352044; 20592581; 21222599; 22422914; 23142962; 23155438 
CHMP4B	16171	128866	Cataract 31, multiple types	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10682967; 10909854; 17701905 
CHN1	1943	1123	Duane retraction syndrome 2	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18653847; 21555619; 21715346 
CHRDL1	29861	91851	Megalocornea 1, X-linked	XL	Pediatric		Ophthalmologic	Ophthalmologic		Individuals may be at risk for manifestations such as cataract development and glaucoma after lenticular dislocation or subluxation, and awareness may allow early management of sequelae	2571565; 22284829; 24073597; 25093588
CHRM3	1952	1131	Eagle-Barrett syndrome	AR	N/A	N/A	Genitourinary; Musculoskeletal; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14797335; 15912376; 22077972
CHRNA1	1955	1134	Myasthenic syndrome, congenital, fast channel; Myasthenic syndrome, slow-channel congenital  	AD/AR	Pediatric	Allelic with Multiple pterygium syndrome, lethal type (AR)	Musculoskeletal; Neurologic	Musculoskeletal; Neurologic; Pharmacogenomic	Manifestations have been reported in heterozygotes 	Most individuals with CMS benefit from AChE inhibitors and/or  potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; For SCCMS, effective treatment has been reported with therapies such as quinidine, fluoxetine, and ephedrine; Additional neurologic monitoring in pregnancy may be beneficial	7254233; 3651795; 7863154; 7619526; 8872460; 9158151; 9221765; 10195214; 12588888; 15079006; 16685696; 18806275; 18252226; 20301347; 23108489
CHRNA2	1956	1135	Epilepsy, nocturnal frontal lobe, type 4	AD	N/A	N/A	Neurologic	General	As the attacks had been interpreted in some instances as being nightmares/sleep walking, genetic diagnosis may be helpful	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16826524; 20301348 
CHRNA4	1958	1137	Epilepsy, nocturnal frontal lobe, type 1	AD	N/A	N/A	Neurologic	General	Mildly affected individuals have been described as frequently undiagnosed/misdiagnosed as nightmares/other sleep disorders, and thus genetic diagnosis may be helpful	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7647781; 7550350; 10563623; 14623738; 20301348; 21753767 
CHRNB1	1961	1140	Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency; Myasthenic syndrome, slow-channel congenital 	AD/AR	Pediatric		Musculoskeletal; Neurologic	Musculoskeletal; Neurologic; Pharmacogenomic		Most individuals with CMS benefit from AChE inhibitors and/or  potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; For SCCMS, effective treatment has been reported with therapies such as quinidine, fluoxetine, and ephedrine	8872460; 8651643; 10562302; 20301347 
CHRNB2	1962	1141	Epilepsy, nocturnal frontal lobe, type 3	AD	N/A	N/A	Neurologic	General	As the attacks had been interpreted in some instances as being nightmares/sleep walking,  a genetic diagnosis may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11062464; 20301348 
CHRND	1965	1144	Myasthenic syndrome, congenital, fast channel; Myasthenic syndrome, slow-channel congenital 	AD/AR	Pediatric	Allelic with Multiple pterygium syndrome, lethal type (AR)	Musculoskeletal; Neurologic	Musculoskeletal; Neurologic; Pharmacogenomic		Most individuals with CMS benefit from AChE inhibitors and/or  potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; For SCCMS, effective treatment has been reported with therapies such as quinidine, fluoxetine, and ephedrine; Additional neurologic monitoring in pregnancy may be beneficial	11435464; 11782989; 18252226; 12499478; 18398509; 23108489
CHRNE	1966	1145	Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency; Myasthenic syndrome, slow-channel congenital 	AD/AR	Pediatric		Musculoskeletal; Neurologic	Musculoskeletal; Neurologic; Pharmacogenomic		Most individuals with CMS benefit from AChE inhibitors and/or  potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; For SCCMS, effective treatment has been reported with therapies such as quinidine, fluoxetine, and ephedrine; Additional neurologic monitoring in pregnancy may be beneficial	8232384; 7538206; 7531341; 8957026; 8872460; 8755487; 9158150; 0514102; 10211467; 10962020; 10534268; 11030414; 12141316; 12034803; 15322984; 16087917; 19064877; 20301347; 20562457; 23108489
CHRNG	1967	1146	Multiple pterygium syndrome; Escobar syndrome	AR	N/A	N/A	Craniofacial; Musculoskeletal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16826520; 16826531; 22167768 
CHST14	24464	113189	Ehlers-Danlos syndrome, musculocontractural type 1	AR	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Ophthalmologic	Hematologic; Musculoskeletal; Ophthalmologic		Clinical issues relate to connective tissue fragility may affect multiple organs, and may include severe bleeding episodes (eg, after minor trauma), such that recognition may allow precautions and preventive measures, as well as rapid treatment in the case of bleeding; Medical treatment (eg, with oral dermatan sulfate) may be beneficial; Due to risk of glaucoma, surveillance may allow early management	9084938; 10766984; 11370633; 16158441; 20004762; 20503305; 20842734; 20533528; 21744491; 22581468; 22407744; 22987394; 23704329
CHST3	1971	9469	Spondyloepiphyseal dysplasia with congenital joint dislocations	AR	N/A	N/A	Cardiovascular; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	112567; 9039660; 15368507; 15098240; 15215498; 17618475; 18513679; 18698629; 19320654; 20830804; 22539336 
CHST6	6938	4166	Macular dystrophy, corneal, 1; Macular dystrophy, corneal, 2	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8684802; 11017086; 11818380; 16207214; 16568029; 17093400; 17896316; 17962390; 19223992; 19365571; 21242781; 21887843 
CHSY1	17198	22856	Temtamy preaxial brachydactyly syndrome	AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic	Audiologic/Otolaryngologic	The condition can include hearing loss, as well as other features and may frequently be clinically recognizable	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	9823490; 21129728; 19952732; 21129727
CHUK	1974	1147	Cocoon syndrome	AR	N/A	N/A	Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic; Pulmonary; Renal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20961246
CIB2	24579	10518	Deafness, autosomal recessive 48; Usher syndrome type IJ	AR	Pediatric		Audiologic/Otolaryngologic; Ophthalmologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	18505454; 23023331 
CIDEC	24229	63924	Lipodystrophy, familial partial, type 5	AR	Pediatric		Cardiovascular; Endocrine; Gastrointestinal	Cardiovascular; Endocrine; Gastrointestinal		Medical treatment of factors such as diabetes, hypertension, and lipid abnormalities may be beneficial to reduce morbidity/mortality; Recognition and treatment of hypertriglyceridemia can help avoid sequelae such as acute pancreatitis	20049731
CIITA	7067	4261	Bare lymphocyte syndrome, type II	AR	Pediatric		Allergy/Immunology/Infectious; Gastrointestinal	Allergy/Immunology/Infectious		Prophylaxis and early and aggressive treatment of infections can be beneficial; BMT has been reported in Bare lymphocyte syndrome, type II	8402893; 9099848; 11862382
CIRH1A	1983	84916	North American Indian childhood cirrhosis	AR	Pediatric		Gastrointestinal	Gastrointestinal		Individuals may initially present with neonatal cholestatic jaundice, and the condition may progress to end-stage, severe liver failure; Liver transplantation has been described as effective, and individuals have been described as dying before liver transplantation was available	6894906; 10820129; 11045837 
CISD2	24212	493856	Wolfram syndrome 2	AR	Pediatric		Audiologic/Otolaryngologic; Endocrine; Gastrointestinal; Genitourinary; Hematologic; Ophthalmologic; Renal	Gastrointestinal; Genitourinary; Hematologic; Renal		Urinary tract anomalies can lead to severe (and potentially avoidable) renal sequelae, including renal failure, and surveillance and early management can be beneficial; Surveillance for and early treatment of bleeding diatheses (as well as related GI disease that can lead to bleeding) can be beneficial	10739754; 11317648; 12116178; 17846994; 22790102; 23429432; 25056293
CITED2	1987	10370	Atrial septal defect 8; Ventricular septal defect 2	AD	N/A	N/A	Cardiovascular	General	Variants may be involved in Premature ovarian failure (AD), but the evidence is unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16287139; 20654020; 22709740; 23082118
CIZ1	16744	25792	Primary cervical dystonia, adult-onset	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22447717
CLCF1	17412	23529	Cold-induced sweating syndrome 2	AR	Pediatric		Musculoskeletal; Neurologic	Neurologic		In the neonatal/early childhood period, the condition can be lethal unless advanced care is instituted; Later, it has been described that cold-induced sweating was alleviated by medical treatment (eg, with clonidine, with lasting effects when co-administered with amitriptyline)	16782820; 20400119
CLCN1	2019	1180	Myotonia congenita, autosomal dominant; Myotonia congenita, autosomal recessive, Myotonia levior	AD/AR	Pediatric		Musculoskeletal	Musculoskeletal; Pharmacogenomic		Individuals may be at increased risk of potentially avoidable/manageable anesthesia reactions, and the disorder may not be clinically highly obvious prior to severe sequelae; Muscle stiffness may respond to medical treatment (eg, mexiletine, tocainide, procainamide, quinine, or phenytoin, as well as other agents); Depolarizing muscle relaxants (eg, suxamethonium), and other agents (eg, adrenaline, beta-adrenergic agonists, propranolol, colchicine) may aggravate myotonia	1670657; 1379744; 7981750; 7951242; 8112288; 7581380; 9040658; 11113225; 11840191; 11933197; 12390967; 12699527; 14639587; 15786415; 17932099; 19185184; 18337100; 20842486; 20301529; 21221019 
CLCN2	2020	1181	Epilepsy, idiopathic, generalized, susceptibility to, 11; Epilepsy, juvenile, absence, suscepibility to, 2;  Epilepsy, juvenile myoclonic, susceptibility to, 8; Leukoencephalopathy with ataxia	AD/AR	N/A	N/A	Neurologic	General	Functional proof of pathogenicity in reported dominant conditions is controversial; As with other forms of epilepsy, optimal seizure control is advantageous	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10888596; 12612585; 19710712; 19191339; 20037607; 23707145
CLCN5	2023	1184	Dent disease 1; Hypophosphatemic rickets, X-linked recessive; Nephrolithiasis, type I; Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis	XL	Pediatric		Endocrine; Renal	Endocrine; Pharmacogenomic; Renal		In Dent disease, surveillance and treatment related to manifestations such as hypercalciuria in order to prevent kidney stones, nephrocalcinosis, and to delay the progression of kidney dysfunction may be beneficial (though efficacy is unclear, treatment may include thiazide diuretics, ACE inhibitors, and ARBs); Vitamin D and phosphorous may be beneficial related to skeletal manifestations; Growth hormone may be indicated; Nephrotoxic agents (eg, NSAIDs, aminoglycosides) should be avoided	14169453; 1908057; 1372109; 7915957; 7922301; 8559248; 9328929; 9062355; 9328927; 9187673; 602200; 15086899; 19673950; 22876375 
CLCN7	2025	1186	Osteopetrosis, autosomal recessive 4; Osteopetrosis, autosomal dominant 2	AD/AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Hematologic; Musculoskeletal; Ophthalmologic	Allergy/Immunology/Infectious; Hematologic; Musculoskeletal		In Autosomal recessive osteopetrosis, early diagnosis can allow medical treatment related to calcium homeostasis, including prevention/treatment of hypocalcemic seizures; Transfusions for hematologic manifestations may be necessary; Individuals may benefit from infectious prophylaxis and early and aggressive treatments of infections; HSCT has been described as beneficial; In autosomal dominant forms, avoidance of high-fracture risk activities can be beneficial 	18131787; 13665485; 4871758; 6546410; 3377922; 2268972; 8358946; 10617161; 11741829; 11207362; 12522560; 13130312; 14584882; 17033731; 17164308; 20301306; 23296056  
CLCNKA	2026	1187	Bartter syndrome, type 4, digenic	AR/Digenic	Pediatric		Audiologic/Otolaryngologic; Renal	Audiologic/Otolaryngologic; Renal	Digenic inheritance (with CLCNKB) has been described	Due to renal salt wasting, individuals can present with dehydration and life-threatening hypotension, and electrolyte management can be beneficial; In some forms, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	15044642; 18310267
CLCNKB	2027	1188	Bartter syndrome, type 3; Bartter syndrome, type 4, digenic	AR/Digenic	Pediatric		Audiologic/Otolaryngologic; Renal	Audiologic/Otolaryngologic; Renal	Digenic inheritance (with CLCNKA) has been described	Due to renal salt wasting, individuals can present with dehydration and life-threatening hypotension, and electrolyte management can be beneficial; In some forms, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	13969763; 9326936; 11102542; 15044642; 18310267; 21162973; 20931281; 19807735; 21479528; 21631963 
CLDN1	2032	9076	Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis	AR	N/A	N/A	Dermatologic; Gastrointestinal	Gastrointestinal		Individuals can have manifest with hepatic disease, and liver transplantation has been described as beneficial; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12164927; 15521008; 16619213; 20645982; 21865982 
CLDN14	2035	23562	Deafness, autosomal recessive 29	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	11163249
CLDN16	2037	10686	Hypomagnesemia 3, renal	AR	Pediatric		Renal	Renal	Some individuals have a self-limiting form of disease	Presentation can include hypocalcemic/hypomagnesemic seizures, and early diagnosis and magnesium therapy can be beneficial; Renal transplantation is frequently necessary	668721; 7637271; 9579153; 10390358; 10878661; 14628289; 16501001; 20607983; 21669885; 21848011; 22422540
CLDN19	2040	149461	Hypomagnesemia 5, renal, with ocular involvement	AR	Pediatric		Ophthalmologic; Renal	Renal		Electrolyte replacement and surveillance for sequelae such as urinary tract infections can be beneficial	500385; 7947033; 17033971; 21030577; 21791920; 22422540;  23301036; 23538362
CLEC7A	14558	64581	Candidiasis, familial, 4	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious	Heterozygous mutations may result in milder manifestations	Individuals are highly susceptible to recurrent fungal infections, and recognition may allow prompt treatment, which may be beneficial	18946062; 19864674; 20807886; 20107226; 22674328; 23374272
CLIC5	13517	53405	Deafness, autosomal recessive 103	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	24781754
CLMP	24039	79827	Congenital short bowel and malrotation syndrome	AR	Pediatric		Gastrointestinal	Gastrointestinal		Individuals have been described as benefiting from early introduction of enteral feeds, with later weaning from parenteral nutrition; Awareness of the risk of other GI-related complications may allow prompt recognition and management	2005514; 10532268; 16707984; 18209785; 22155368
CLN3	2074	1201	Ceroid lipofuscinosis, neuronal, 3	AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General	Levodopa treatment may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7426545; 1609833; 1319116; 7553855; 7887420; 9004140; 9311735; 9450775; 10477428; 11342698; 15965709; 17947292; 19135632; 19489875; 21990111 
CLN5	2076	1203	Ceroid lipofuscinosis, neuronal, 5	AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7133332; 1649978; 9662406; 15965709; 15728307; 17607606; 19309691; 20157158
CLN6	2077	54982	Ceroid lipofuscinosis, neuronal, 6	AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13822848; 5478271; 760366; 3284607; 7668317; 10929274; 11791207; 11727201; 15965709; 15996215; 19520283; 21549341; 21990111; 22883287; 23180398; 23735787
CLN8	2079	2055	Ceroid lipofuscinosis, neuronal, 8; Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant	AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10508524; 10191125; 11589000; 15024724; 15074367; 16570191; 17129765; 17560505; 19431184; 19807737; 21990111; 22220808; 22964447 
CLP1	16999	10978	Pontocerebellar hypoplasia type 10	AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24766809; 24766810
CLPP	2084	8192	Deafness, autosomal recessive 81	AR	Pediatric		Audiologic/Otolaryngologic; Endocrine; Neurologic; Obstetric	Audiologic/Otolaryngologic; Obstetric		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Genetic knowledge may allow fertility preservation such as by storing eggs	17690910; 22037954; 23541340
CLRN1	12605	7401	Retinitis pigmentosa 61; Usher sydnrome, type 3A	AR	N/A	N/A	Audiologic/Otolaryngologic; Ophthalmologic	General	Hearing loss has been reported to be postlingual	 Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7711740; 8975700; 9719374; 11524702; 12080385; 12145752; 14569126; 15521980; 19753315; 21310491; 21675857 
CNBP	13164	7555	Myotonic dystrophy 2	AD	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Obstetric; Ophthalmologic	Cardiovascular	Individuals with bi-allelic mutations and severe cardiac manifestations have been described	The condition can include cardiovascular manifestions, including arrhythmias (sudden cardiac death has been reported), left ventricular dysfunction, and congestive heart failure, and surveillance (eg, with EKG and echocardiogram), as well as early interventions and medical management, may decrease morbidity and mortality	10078095; 11486088; 12970845; 12601109; 14505273; 15503094; 15503094; 15623712; 16258778; 16684600; 18057971; 19020295; 19481939; 20301639; 20627570; 22587749; 23561036
CNGA1	2148	1259	Retinitis pigmentosa 49	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7479749
CNGA3	2150	1261	Achromatopsia 2; Leber congenital amaurosis	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9662398; 11536077; 15059731; 15980212; 16961972; 18636117; 20454696; 21901789; 21911670; 21912902; 23362848 
CNGB1	2151	1258	Retinitis pigmentosa 45	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11379879; 15557452; 20126465 
CNGB3	2153	54714	Achromatopsia 3; Macular degeneration, juvenile 	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4192495; 1347967; 10888875; 15712225; 17265047; 17652762; 19767295; 20454696; 23362848 
CNNM2	103	54805	Hypomagnesemia 6 ,renal	AR	Pediatric		Renal	Renal		Correction of electrolyte abnormalities may help treatment, though complete correction was not achieved in some described individuals	12584272; 21397062
CNNM4	105	26504	Jalili syndrome	AR	N/A	N/A	Dental; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3236352; 15173235; 19200525; 19200527; 20706282 
CNTN1	2171	1272	Myopathy, congenital, Compton-North	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12899872; 19026398
CNTN2	2172	6900	Epilepsy, familial adult myoclonic 5	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23518707
CNTNAP2	13830	26047	Cortical dysplasia-focal epilepsy syndrome; Pitt-Hopkins like syndrome 1	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16571880; 19896112; 19582487
COA5	33848	493753	Mitochondrial complex IV deficiency	AR	N/A	N/A	Biochemical; Cardiovascular	General	Manifestations include lethal neonatal hypertrophic cardiomyopathy	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21457908
COASY	29932	80347	Neurodegeneration with brain iron accumulation 6	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24360804
COCH	2180	1690	Deafness, autosomal dominant 9	AD	N/A	N/A	Audiologic/Otolaryngologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8817345; 9806553; 10400989; 14512963; 16261627; 18312449; 19161137; 20447147; 21046548; 21052762; 21774451; 22610276; 22931125 
COG1	6545	9382	Congenital disorder of glycosylation, type IIg	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	Hematologic	The condition can include cardiac manifestations as well as other multi-system manifestations; Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	16537452; 19008299
COG4	18620	25839	Congenital disorder of glycosylation, type IIj	AR	Pediatric		Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Hematologic; Neurologic 	Allergy/Immunology/Infectious; Hematologic	Hepatic-metabolized agents should be avoided	The condition can include recurrent respiratory infections as well as other multi-systemic manifestations, and precautions may be beneficial; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	19494034
COG5	14857	10466	Congenital disorder of glycosylation, type IIi	AR	Pediatric		Biochemical; Neurologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	19690088
COG6	18621	57511	Congenital disorder of glycosylation, type Iil	AR	Pediatric	Allelic with Shaheen syndrome (AR)	Biochemical; Dermatologic; Hematologic; Neurologic	Hematologic	Hepatic-metabolized agents should be avoided	A described individual presented with neurological manifestations as well as vitamin K deficiency and intracranial bleeding; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	20605848; 23606727
COG7	18622	91949	Congenital disorder of glycosylation, type IIe	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	15107842; 17356545; 19577670
COG8	18623	84342	Congenital disorder of glycosylation, type IIh	AR	Pediatric		Biochemical; Hematologic; Neurologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	17220172; 17331980; 20301507 
COL10A1	2185	1300	Metaphyseal chondrodysplasia, Schmid type	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14279845; 3281118; 8220429; 7936797; 8782043; 9837818; 10929364; 12554676; 15578582; 14227699; 17403716; 20872587; 21360259; 21447328 
COL11A1	2186	1301	Stickler syndrome, type II; Fibrochondrogenesis; Marshall syndrome	AD/AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic	Audiologic/Otolaryngologic; Ophthalmologic		Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Avoidance of risk factors related to ocular manifestations (eg, contact sports) is indicated	13520885; 749746; 6694183; 6507479; 6507478; 8733059; 8872475; 9129742; 10573014; 9529347; 9475607; 10486316; 15286167; 17236192; 21035103; 20301479 
COL11A2	2187	1302	Deafness, autosomal dominant 13; Deafness, autosomal recessive 53; Fibrochondrogenesis 2; Weissenbacher-Zweymuller syndrome;  Otospondylomegaepiphyseal dysplasia; Stickler syndrome, type III	AD/AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic	Audiologic/Otolaryngologic; Ophthalmologic		Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Avoidance of risk factors related to ocular manifestations (eg, contact sports) is indicated	14234962; 7833911; 7859284; 9805126; 9506662; 10581026; 10677296; 15372529; 16033917; 22246659
COL17A1	2194	1308	Epidermolysis bullosa, junctional, non-Herlitz type	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7883981; 7550320; 9038345; 17263807; 17596158; 19369679; 20301304; 21357940; 21466533 
COL18A1	2195	80781	Knobloch syndrome 1	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1554013; 7802003; 10942434; 14695535; 17546652; 19160445; 20799329; 21085708; 21862674; 21937992
COL1A1	2197	1277	Ehlers-Danlos syndrome, type VII, autosomal dominant; Ehlers-Danlos syndrome, type I	AD	Pediatric	Allelic with Caffey disease (AD); Osteogenesis imperfecta, types I, II, III, and IV (AD): in OI, medical treatment (eg, with pamidronate) may be beneficial, but evidence does not show that early (genetic) diagnosis would necessarily be beneficial	Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Musculoskeletal; Obstetric; Ophthalmologic	Cardiovascular; Obstetric		Individuals may have aortic root dilatation (as well as arterial/vascular fragility), but the natural history is unclear, and many not commonly progress, though yearly surveillance with echocardiogram when aortic dilatation or mitral valve prolapse is peresent has been recommended; Precautions in pregnancy may be beneficial	1146889; 1054840; 6304100; 3001313; 3016737; 3082886; 3722186; 3940669; 3108247; 3667599; 3403550; 3341380; 2745420; 2511192; 2794057; 2767050; 2777808 ; 2309707; 2121988; 2339700; 2295701; 1867198; 2037280; 1301191; 1353940; 8408653; 7789952; 9007315; 8757037; 8723681; 8613526; 8910493; 9386671; 9295084; 9067755; 9101290; 9143923; 9753709; 9753715; 10417276; 10739762; 10843163; 11286507; 11760017; 11668615; 11970931; 11704682; 12417561; 12417568; 12524541; 12629073; 12728084; 15024692; 15241796; 15728585; 15864348; 16272059;  16291701; 16434452; 16778601; 17078022; 17211858; 17217883; 17309652; 18409203; 18553566; 18996919; 19929435; 20087402; 21667357; 22206639; 22565191; 22791419; 22795108; 22855962; 22987783; 23072183; 23118688; 23682531; 23692737
COL1A2	2198	1278	Ehlers-Danlos syndrome, cardiac valvular form 	AR	Pediatric	Allelic with Osteogenesis imperfecta, types II,III, and IV (AD) (for which medical treatment (eg, with pamidronate) may be beneficial, but evidence does not show that early (genetic) diagnosis would necessarily advantageous in terms of medical treatment); Ehlers-Danlos syndrome, type VII, autosomal dominant (AD)	Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Musculoskeletal; Ophthalmologic	Cardiovascular		The condition may be difficult to recognize, and cardiac manifestations, which can include arrhythmias may benefit from early (including surgical) interventions;  Some individuals may also have arterial/vascular fragility, and awareness may allow appropriate precautions and prompt management of sequelae	4742738; 6773953; 3940669; 2952379; 3621666; 3680255; 2454224; 2897363; 2777808; 1712342; 1301191; 1577745; 7916744; 8071956; 8950681; 9386671; 9295084; 9099837; 9753709; 10843163; 11760017; 11970931; 12417561; 12417568; 12629073; 12728084; 15241796; 15077201; 16778601; 16816023; 16434452; 17217883; 18996919; 19208385; 20087402; 21667357; 22206639; 22791419; 22795120; 23118688; 23692737
COL27A1	22986	85301	Steel syndrome	AR	Pediatric		Craniofacial; Musculoskeletal	Musculoskeletal		Outcomes have been described as better without the use of surgical treatment for hip dislocations	8423186; 24986830
COL2A1	2200	1280	Stickler syndrome, type I; Rhegmatogenous retinal detachment, autosomal dominant; Czech dysplasia; Otospondylomegaepiphyseal dysplasia; Epiphyseal dysplasia, multiple, with myopia and deafness; Avascular necrosis of femoral head, primary	AD	Pediatric	Allelic with: Achondrogenesis, type II (AD); Hypochondrogenesis (AD); Spondyloepimetaphyseal dysplasia, Strudwick type (AD); Spondyloepimetaphyseal dysplasia, Namaqualand type (AD); Spondyloepiphyseal dysplasia congenita (AD); Kniest dysplasia (AD); Platyspondylic skeletal dysplasia, Torrance type (AD); Vitreoretinopathy with phalangeal epiphyseal dysplasia (AD); Legg-Calve-Perthes disease (AD); Osteoarthritis with mild chondrodysplasia (AD); Spondyloperipheral dysplasia (AD)	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic	Audiologic/Otolaryngologic; Ophthalmologic	The condition can include varying degrees/types of early hearing loss in some conditions, such as Stickler syndrome and Otospondylomegaepiphyseal dysplasia , while in others, such as Czech dysplasia, the hearing loss typically occurs much later	Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Avoidance of risk factors related to ocular manifestations (eg, contact sports) is indicated; In Avascular necrosis of femoral head, primary, identifying carriers before the onset of clinical symptoms can allow interventions in order to delay disease progression 	14299791; 5582025; 4568361; 4214536; 699354; 514691; 7036745; 6628450; 6496567; 4014370; 3728560; 2572591; 1975693; 2300123; 1677770; 1671807; 1429602; 1444917; 8434604; 8325895; 8317498; 8737653; 7981752; 7700721; 7874117; 7757081; 7550321; 7847372; 8737653; 8723097; 9800905; 10486316; 10406661; 10745044; 10982970; 11812423; 12939326; 12544472; 12884428; Kozlowski 2004; 15895462; 15316962; 14729840; 15930420; 16189708; 15671297; 15316962; 16088915; 15643621; 17726487; 16752401; 16155195; 17394019; 17437277; 17509551; 17721977; 18553548; 19764028 ; 20131279; 20583175; 20513134; 21671384; 21204228; 20301479; 21924244; 21332586; 20179744 
COL3A1	2201	1281	Ehlers-Danlos syndrome, type IV	AD	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Obstetric	Cardiovascular; Obstetric	Homozygous mutations have been reported; An individual with EDS type III with a COL3A1 mutation has been reported 	Individuals are at risk for manifestations such as bowel and arterial ruptures, as well as severe pregnancy-related complications in women, and surveillance (eg, arterial screening by CT or MRI) and early recognition may allow precautionary measures prompt recognition and treatment of manifestions, which may reduce morbidity and mortality	7230200; 6129381; 3204406; 3337712; 2321591; 2349939; 2243125;  1496983; 1352273; 1557695; 8317500; 7833919; 8526472; 10051163; 10928897; 10706896; 11577371; 12131463; 12786757; 15007000; 19455184; 20301667; 21637106; 22713205; 23052746; 23688910
COL4A1	2202	1282	Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps; Brain small vessel disease with or without ocular anomalies; Anterior segment dysgenesis with  cerebral involvement; Porencephaly 1; Schizencephaly	AD	Adult		Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Cardiovascular; Pharmacogenomic		Trauma at birth and during adulthood, as well as issues such as hypertension and exercise-induced stress is a stronger risk factor for intracerebral hemorrhage than in persons without mutations; Anticoagulant use may exacerbate the stroke risk associated with COL4A1 mutations.	6428250; 12525718; 15136694; 15905400; 15882279; 17030722; 16598045; 18160688; 17696175; 19949034; 19194877; 20056676; 22522439; 23225343; 23394911; 24628545
COL4A2	2203	1284	Hemorrhage, intracerebral, susceptibility to	AD	Adult	Allelic with Porencephaly 2 (AD)	Cardiovascular	Cardiovascular	Authors have suggested that reported nonglycine variants may result in milder disease later in life or cause disease due to interactions with other factors.	The awareness that individuals are at risk for hemorrhagic stroke may allow preventive management related to contributory factors, which may decrease morbidity/mortality.	22209247; 22209246
COL4A3	2204	1285	Alport syndrome, autosomal recessive	AD/AR	Pediatric	Allelic with Hematuria, benign familial (AD)	Audiologic/Otolaryngologic; Ophthalmologic; Renal	Ophthalmologic; Renal		In Alport syndrome, medical treatment related to renal sequelae (eg, with ACE inhibitors, ARBs) may be beneficial related to delaying renal failure, as well as with overall life expectancy, though dialysis/renal transplantation may be required; Corneal protection may be beneficial in individuals with recurrent corneal erosions	7033680; 7987301; 8196274; 7987396; 7783412; 7783419; 9195222; 9269635; 11961012; 11134255; 20301386; 22166847; 22237748; 22811928; 22997344
COL4A4	2206	1286	Alport syndrome, autosomal recessive	AD/AR	Pediatric	Allelic with Hematuria, benign familial (AD)	Audiologic/Otolaryngologic; Ophthalmologic; Renal	Ophthalmologic; Renal		In Alport syndrome, medical treatment related to renal sequelae (eg, with ACE inhibitors, ARBs) may be beneficial related to delaying renal failure, as well as with overall life expectancy, though dialysis/renal transplantation may be required; Corneal protection may be beneficial in individuals with recurrent corneal erosions	7033680; 7987396; 7783412; 8787673; 9195222; 20301386; 22166847; 22237748; 22811928; 22997344
COL4A5	2207	1287	Alport syndrome, X-linked	XL	Pediatric		Audiologic/Otolaryngologic; Ophthalmologic; Renal	Ophthalmologic; Renal	Treatment of renal issues (eg, with antihypertensive agents, ACE inhibitors, etc.) can be helpful, but does not appear to affect natural history	In Alport syndrome, medical treatment related to renal sequelae (eg, with ACE inhibitors, ARBs) may be beneficial related to delaying renal failure, as well as with overall life expectancy, though dialysis/renal transplantation may be required; Corneal protection may be beneficial in individuals with recurrent corneal erosions	20773074; 14856448; 626446; 7033680; 3728466; 2349482; 1483700; 1635357; 1598909; 7706490; 8825605; 8651292; 8940267; 8651296; 9195222; 20881942; 21505094; 21848006; 21897443; 21332469;  22166944; 20301386; 22166847; 22237748; 22335431; 22811928; 22921432; 22919268; 22997344
COL4A6	2208	1288	Deafness, X-linked, with cochlear malformation	XL	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	23714752
COL5A1	2209	1289	Ehlers-Danlos syndrome, type I; Ehlers-Danlos syndrome, type II	AD	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Musculoskeletal; Obstetric; Ophthalmologic	Cardiovascular; Obstetric	Homozygous mutations have been reported	Individuals may have aortic root dilatation, but the natural history is unclear, and may not typically progress, though yearly surveillance with echocardiogram when aortic dilatation or mitral valve prolapse is peresent has been recommended; Precautions in pregnancy may be beneficial	8541855; 8923000; 9042913; 10602121; 10777716; 11992482; 12180144; 15264295; 15580559; 18972565; 20635400; 20847697; 20301422; 21611149; 22696272 
COL5A2	2210	1290	Ehlers-Danlos syndrome, type I; Ehlers-Danlos syndrome, type II	AD	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Musculoskeletal; Obstetric; Ophthalmologic	Cardiovascular; Obstetric		Individuals may have aortic root dilatation, but the natural history is unclear, and may not typically progress, though yearly surveillance with echocardiogram when aortic dilatation or mitral valve prolapse is peresent has been recommended; Precautions in pregnancy may be beneficial	9425231; 9783710; 12180144; 16278879; 15580559; 20301422; 20847697 
COL6A1	2211	1291	Ullrich congenital muscular dystrophy; Bethlem myopathy	AD/AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	963533; 3632670; 8782832; 11932968; 12840783; 12958705; 16130093; 15689448; 15955946; 17785674; 17886299; 18362356; 18366090; 19564581; 20301676; 20976770
COL6A2	2212	1292	Ullrich congenital muscular dystrophy ; Myosclerosis, congenital; Bethlem myopathy; Epilepsy, progressive myoclonic, autosomal recessive	AD/AR	N/A	N/A	Musculoskeletal; Neurologic	General	Medical treatment (eg, with Cyclosporin A) may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	963533; 11381124; 12297580; 15563506; 15689448; 16075202; 15955946; 17886299; 18852439; 19564581; 20106987; 20302629; 20301676; 21280092; 23138527 
COL6A3	2213	1293	Ullrich congenital muscular dystrophy; Bethlem myopathy 	AD/AR	N/A	N/A	Musculoskeletal	General	Medical treatment (eg, with Cyclosporin A) may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	963533; 11992252; 15563506; 15689448; 16141002; 17886299; 18362356; 18366090; 19564581; 20301676; 20976770; 21496625; 21943391; 22526018 
COL7A1	2214	1294	Epidermolysis bullosa dystrophica, autosomal recessive; Epidermolysis bullosa dystrophica, autosomal dominant; Epidermolysis bullosa dystrophica inversia; Epidermolysis bullosa pruriginosa; Nail disorder, nonsyndromic congenital, 8; Epidermolysis bullosa dystrophica, Bart type; Epidermolysis bullosa, pretibial; Transient bullous dermolysis of the newborn 	AD/AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1347297; 1680286; 8513326; 8345225; 8245264; 8170945; 8037207; 8541842; 7577595; 8644729; 9406826; 9347800; 9182828; 9856844; 9892921; 10583163; 10383749; 10469344; 12485454; 11874498; 11843659; 12787275; 16225626; 16965329; 17434045; 16971478; 20574443; 20920254; 21113014; 21182502; 21196708; 21352278; 21382783; 21574979; 21629976; 21849769; 21967228; 22058051; 22266148; 22515571; 22854212; 22909362; 22974128; 23013315 
COL8A2	2216	1296	Corneal dystrophy polymorphous posterior, 2; Corneal dystrophy, Fuchs endothelial, 1	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	399801; 11689488; 15914606; 18024822; 18464802 
COL9A1	2217	1297	Stickler syndrome, type IV	AR	Pediatric	Allelic with Epiphyseal dysplasia, multiple, 6 (AD)	Audiologic/Otolaryngologic; Craniofacial;Musculoskeletal; Ophthalmologic	Audiologic/Otolaryngologic; Ophthalmologic		Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Avoidance of risk factors related to ocular manifestations (eg, contact sports) is indicated	11565064; 16909383; 20301479 
COL9A2	2218	1298	Stickler syndrome, Type V	AR	Pediatric	Allelic with Epiphyseal dysplasia, multiple, 2 (AD)	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic	Audiologic/Otolaryngologic; Ophthalmologic		Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Avoidance of risk factors related to ocular manifestations (eg, contact sports) is indicated	3238439; 8528240; 12244547; 15633184; 20358595; 21671392; 20301479 
COL9A3	2219	1299	Epiphyseal dysplasia, multiple, 3	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10090888; 10655510; 15551337; 20301302 
COLEC11	17213	78989	3MC syndrome 2	AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Audiologic/Otolaryngologic	The condition can involve multiple congenital anomalies	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	2569826; 8933348; 21258343 
COLQ	2226	8292	Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency	AR	Pediatric		Musculoskeletal; Neurologic	Musculoskeletal; Neurologic; Pharmacogenomic	Endplate acetylcholinesterase deficiency has been reported as nonresponsive to treatment	Most individuals with CMS benefit from AChE inhibitors and/or  potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; Some individuals with SCCMS are treated with quinidine, which has some major side effects and may be detrimental in individuals with AChR deficiency; Additional neurologic monitoring in pregnancy may be beneficial	9758617; 9689136; 10441569; 11865139; 23108489
COMP	2227	1311	Pseudoachondroplasia; Multiple ephiphyseal dysplasia	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13633894; 3314506; 7907311; 7670471; 7670472; 8725795; 9021009; 9188668; 9887340; 11968079; 14684695; 15266613; 15551305; 17579668; 20301302; 20830670; 21599986; 21644213; 21922596; 21965141; 22006726 
COMT	2228	1312	Medication response, association with	AD	Pediatric		General	Pharmacogenomic		Variants may involve clinically relevant drug metabolism	12716966; 15927391; 16876132; 17522626; 17644310; 18214865; 19462300; 19858760; 20053459; 20071037; 20216107; 20591499; 20877297; 21280081; 21788083; 22417933; 22483292 
COQ2	25223	27235	Coenzyme Q10 deficiency; COQ2-associated nephropathy	AR	Pediatric		Biochemical; Musculoskeletal; Neurologic; Renal	Biochemical	A heterogenous group of disorders has been described, but the molecular etiologies of some are unclear; Variants may contribute to Multiple system atrophy, susceptibility to 1 (AR)	Treatment with coenzyme Q10 has been described as beneficial	16116126; 17855635; 17374725; 17332895; 17420317; 23758206; 24988567; 24988570
COQ6	20233	51004	Coenzyme Q10 deficiency 6	AR	Pediatric		Biochemical; Musculoskeletal; Neurologic; Renal	Biochemical	A heterogenous group of disorders has been described, but the molecular etiologies of some are unclear	Some patients have been reported as showing a favorable response to oral Coenzyme Q supplementation	21540551
COQ9	25302	57017	Coenzyme Q10 deficiency	AR	Pediatric		Biochemical; Musculoskeletal; Neurologic; Renal	Biochemical	A heterogenous group of disorders has been described, but the molecular etiologies of some are unclear	Treatment with coenzyme Q10 can be beneficial	11562630; 19375058
CORIN	19012	10699	Preeclampsia/eclampsia 5	AD	Pediatric		Obstetric	Obstetric		Individuals may be at high risk for pregnancy complications such as preeclampsia/eclampsia, and thus preconception planning, surveillance during pregnancy  (eg, including related to proteinuria, hypertension, liver function, and hematologic parameters), as well as delivery planning may be beneficial in order to decrease associated morbidity and mortality	22437503
CORO1A	2252	11151	Immunodeficiency 8	AR	Pediatric		Allergy/Immunology/Infectious; Oncologic	Allergy/Immunology/Infectious; Oncologic		The condition can involve recurrent infections, and awareness may allow preventive measures, and early and aggressive treatment of infections; Individuals have been described with oncologic sequelae of infections (such as EBV-related lymphoproliferative disorders) and awareness may allow prompt diagnosis and management; BMT has been described	19097825; 23522482; 25073507
COX10	2260	1352	Mitochondrial complex IV deficiency; Leigh syndrome	AR	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Hematologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10767350
COX14	28216	84987	Mitochondrial complex IV deficiency	AR	N/A	N/A	Cardiovascular; Biochemical; Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22243966
COX15	2263	1355	Leigh syndrome; Cardiomyopathy, hypertrophic, early-onset fatal	AR	N/A	N/A	Biochemical; Cardiovascular; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2175025; 12474143; 15235026; 15863660; 21412973 
COX20	26970	116228	Mitochondrial complex IV deficiency	AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23125284; 24202787
COX4I2	16232	84701	Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis	AR	Pediatric		Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic	Gastrointestinal		Pancreatic enzyme supplementation has been reported to improve psychomotor development, as well as direct sequelae such as steatorrhea	19268275
COX6A1	2277	1337	Charcot-Marie-Tooth disease, recessive intermediate D	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	25152455
COX6B1	2280	1340	Mitochondrial complex IV deficiency	AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18499082
COX7B	2291	1349	Aplasia cutis congenita, reticulolinear, with microcephaly, facial dysmorphism and other congenital anomalies	XL	N/A	N/A	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9747372; 23122588
CP	2295	1356	Aceruloplasminemia; Hypoceruloplasminemia	AR	Pediatric		Biochemical; Endocrine; Gastrointestinal; Neurologic; Ophthalmologic	Biochemical		In Aceruloplasminemia, medical management can be beneficial (eg, with iron chelating agents to decrease serum ferritin, brain and liver iron stores, and prevent progression of neurologic signs/symptoms; Combined IV desferrioxamine and fresh-frozen plasma can decrease liver iron content; repetitive FFP treatment can improve neurologic manifestations; antioxidants and oral zinc and deferasirox may prevent tissue damage to the liver and pancreas	3574673; 1458725; 7820540; 7539672; 9066364; 20301666 
CPA6	17245	57094	Febrile seizures, familial, 11; Epilepsy, familial temporal lobe, 5	AD/AR	N/A	N/A	Neurologic	General	As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21922598; 23105115
CPN1	2312	1369	Carboxypeptidase N deficiency	AR	N/A	N/A	Allergy/Immunology/Infectious	General	Heterozygotes may demonstrate milder manifestations	The consequences of the condition are unclear, though genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7437116; 12560874; 18068674
CPOX	2321	1371	Coproporphyria; Harderoporphyria	AD/AR	Pediatric		Gastrointestinal; Hematologic; Neurologic	Hematologic; Pharmacogenomic		In Coprophyria, attacks may be precipitated by a variety of agents (eg, fasting, as well as specific pharmaceutical agents, including oral contraceptives), which should be avoided; IV therapy (with heme arginate) has been described as effective;  In heterozygotes, specific considerations are important in surgery (eg, use of IV glucose perioperatively) and related to agent selection for anesthesia induction; Liver transplanation has been described; In Harderoporphyria, individuals may suffer from neonatal hemolytic anemia, which may necessitate RBC transfusions	14378650; 5838412; 4163920; 4393048; 74745; 6886003; 6502649; 6143037; 8012360; 8286403; 7757079; 11309681; 12227458; 12181641; 16151909; 16159891; 21103937; 23236641 
CPS1	2323	1373	Carbamoylphosphate synthetase I deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical; Pharmacogenomic		Specific urgent and long-term medical management (eg, dietary measures, arginine, sodium benzoate, sodium phenylbutyrate), as well as measures such as dialysis when necessary, may be beneficial to reduce morbidity and mortality; Avoidance of certain agents (eg, valproate), as well as special considerations in situations such as peregnancy, are warranted due to potential adverse events	5356974; 5471650; 4111816; 4811018; 7078580; 6427608; 3759432; 3792387; 1414247; 8486760; 8273985; 9711878; 21120950; 16708072; 17310273; 19793055; 21120950; 22173106
CPT1A	2328	1374	Carnitine palmitoyltransferase deficiency I	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Renal	Biochemical; Pharmacogenomic		Dietary management, including avoidance of fasting and prompt treatment of hypoglycemia, can prevent and treat metabolic decompensation, and can prevent neurologic damage; Surveillance for hepatic dysfunction may be beneficial, and potentially hepatoxic agents should be avoided	7014807; 3211616; 1598098; 1403388; 9691089; 10625081; 11286380; 11350182; 12189492; 15110323; 20301700; 20696606; 21962599 
CPT2	2330	1376	Carnitine palmitoyltransferase II deficiency	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Musculoskeletal; Renal	Biochemical; Musculoskeletal; Pharmacogenomic; Renal		There are diverse presentations, including a lethal neonatal, severe infantile hepatocardiomuscular, and myopathic forms, and optimal treatment may vary according to the phenotype; Severe, life-threatening rhabdomyolytic episodes can be precipitated by illness, prolonged exercise, dehydration, or fasting, and medical therapy (eg, with fibrates), along with avoidance of these precipitating factors (and interventions such as IV glucose in the instance of acute episodes) can be beneficial; Dietary measures (high-carbohydrate/low-fat diet) and medications (eg, carnitine) can be beneficial; Certain medications should be avoided, including valproate, general anesthesia, ibuprofen, and high-dose diazepam	5416202; 123038; 187736; 736528; 272487; 2748260; 2712755; 1999498; 1940982; 1528846; 8358442; 8201482; 8651281; 8786066; 8682496; 11389301; 11477613; 11595519; 12410208;  12673791; 15363638; 15642848; 15622536; 18471680; 18550408; 18925671; 19228633; 19335026; 20661589; 20301431; 20505667; 20543534; 20810031; 21641254; 21913903; 23184072; 23326270
CR1	2334	1378	Blood group, Knops system	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	11724985
CR2	2336	1380	Common variable immune deficiency, 7	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	22035880
CRADD	2340	8738	Mental retardation, autosomal recessive 34	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22279524
CRB1	2343	23418	Leber congenital amaurosis 8; Retinitis pigmentosa 12, autosomal recessive; Pigmented paravenous chorioretinal atrophy 	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	434087; 6614113; 3778279; 2801856; 10508521; 11389483; 15024725; 15623792; 16543197; 16564825; 19140180; 20006823; 21484995; 22065545; 22277662; 23077403; 23379534 
CRBN	30185	51185	Mental retardation, autosomal recessive 2	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10932263; 15557513; 17036314; 17380424
CREBBP	2348	1387	Rubinstein-Taybi syndrome	AD	Pediatric		Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic ; Oncologic; Ophthalmologic	Allergy/Immunology/Infectious; Hematologic; Cardiovascular; Oncologic; Ophthalmologic		The condition can include a risk of frequent infections (especially respiratory infections), and prophylaxis and early and aggressive treatment of infetions may be beneficial; There may be increased risk of malignancy, and awareness may allow early detection and treatment of oncologic processes; Due to the possibility of cardiovascular anomalies (including arrhythmia),  surveillance may be beneficial; Surveillance for certain types of ophthalmologic manifestations (eg, glaucoma) may be beneficial in order to allow prompt treatment	13983033; 7137629; 7747773; 7630403; 10573006; 15706485; 16913274; 18792986; 19852432; 20301699; 20717166; 20949605; 21085895; 21189944; 22426292; 23432975
CRELD1	14630	78987	Atrioventricular septal defect, partial, with or without heterotaxy	AD	N/A	N/A	Cardiovascular; Gastrointestinal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12632326; 15857420; 21080147; 22740159 
CRIPT	14312	9419	Short stature with microcephaly and distinctive facies	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24389050
CRLF1	2364	9244	Crisponi syndrome; Cold-induced sweating syndrome, type 1 	AR	Pediatric		Musculoskeletal; Neurologic	Neurologic		In the neonatal/early childhood period, the condition can be lethal unless advanced care is instituted; Later, it has been described that cold-induced sweating was alleviated by medical treatment (eg, with clonidine)	8723066; 12509788; 17436252; 17436251; 18837055; 19012339; 20186812; 20400119; 21326283; 21370513; 23026229 
CRTAP	2379	10491	Osteogenesis imperfecta, type VII	AR	N/A	N/A	Musculoskeletal; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12110406; 17192541; 17055431; 19862557; 21955071; 21964860; 23613367
CRX	2383	1406	Leber congenital amaurosis 7; Cone-rod retinal dystrophy 2	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9390563; 9390562; 9537410; 9931337; 12208271; 15531334; 20301475; 20301590; 20513135; 22960069 
CRYAA	2388	1409	Cataract 9 multiple types	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9467006; 11006246; 14512969; 16564818; 17296897; 18302245; 20465443; 20606865; 21866213; 22065922; 22216983 
CRYAB	2389	1410	Myopathy, myofibrillar, 2; Cardiomyopathy, dilated, 1II; Congenital cataract and cardiomyopathy; Cataract, myofibrillar myopathy and cardiomyopathy	AD	Pediatric	Allelic with Cataract, posterior polar, 2 (AD); Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related (AR)	Cardiovascular; Musculoskeletal; Ophthalmologic	Cardiovascular	Individuals have been described with a combination of cardiovascular, musculoskeletal, and ophthalmologic manifestations, as well as apparently isolated findings affecting each of these organ systems	Individuals with Myopathy, myofibrillar, 2 typically present with slowly progressive weakness, and a significant proportion of individuals demonstrate cardiomyopathy, such that surveillance for arrhythmia or conduction defects may allow early treatment (eg, pacemaker, ICD); Cardiac transplantation may be necessary in individuals with severe forms of cardiomyopathy; Individuals with Cardiomyopathy, dilated, 1II may present with arrhythmias, including sequelae such as sudden cardiac death, and surveillance (eg, with electrocardiogram and echocardiogram) may allow early management as described for other CRYAB-related cardiac manifestations	570292; 8000975; 9731540; 11577372; 14681890; 16483541; 16793013; 20301672; 21337604; 21920752; 23197161; 23590293
CRYBA1	2394	1411	Cataract 10, multiple types	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7573044; 9788845; 17653060; 20142846; 21686330; 21850182; 21866213; 22665976 
CRYBA2	2395	1412	Cataract 42	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23508780
CRYBA4	2396	1413	Cataract 23	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16960806; 20577656 
CRYBB1	2397	1414	Cataract, congenital nuclear, autosomal recessive 3; Cataract, pulvurent	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12360425; 17460281; 21972112 
CRYBB2	2398	1415	Cataract, sutural, with punctate and cerulean opacities; Cataract, Coppock-like; Cataract, congenital, cerulean type, 2	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2240043; 8812489; 9158139; 10634616; 11424921; 17234267; 18617901; 19649175; 21031021; 21245961; 22312185; 22846113 
CRYBB3	2400	1417	Cataract, congenital nuclear, autosomal recessive, 2	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15914629
CRYGB	2409	1419	Cataract 39, multiple types	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23288985
CRYGC	2410	1420	Cataract 2, multiple types	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8190472; 10521291; 10914683; 12011157; 18587492; 18618005; 19204787; 22052681; 22876111 
CRYGD	2411	1421	Cataract 4, multiple types	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8733140; 10521291; 9927684; 10915766; 12567263; 12011157; 12676897; 17564961; 18587492; 19262743; 19633732; 19668596; 20508808; 21031598; 21552497; 21866214; 22219628; 22669729 
CRYGS	2417	1427	Cataract, progressive polymorphic cortical	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16141006
CSF1R	2433	1436	Leukoencephalopathy, diffuse hereditary, with spheroids	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16523341; 19153373; 22197934; 22843259; 23698128
CSF2RA	2435	1438	Surfactant metabolism dysfunction, pulmonary, 4	XL	Pediatric		Pulmonary	Pulmonary		The condition manifests with childhood-onset respiratory insufficiency due to pulmonary alveolar proteinosis , and treatment with  whole-lung lavage has been reported as beneficial; It has additionally been reported that diagnosis has important therapeutic implications, as BMT/HSCT can be effective	18955567; 18955570; 20622029 
CSF2RB	2436	1439	Surfactant metabolism dysfunction, pulmonary, 5	AR	Pediatric		Pulmonary	Pulmonary		The condition typically manifests with childhood-onset respiratory insufficiency (though adult-onset disease has also been reported) due to pulmonary alveolar proteinosis, and whole-lung lavage may be beneficial;  It has been reported that diagnosis has important therapeutic implications, as BMT/HSCT can be effective	9410898; 21075760
CSF3R	2439	1441	Neutrophilia, hereditary	AD	N/A	N/A	Hematologic	General	One individual has been described as developing a myelodysplastic syndrome with refractory anemia	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4825608; 19620628
CSNK1D	2452	1453	Advanced sleep-phase syndrome, familial, 2	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	 15800623; 23636092
CSPP1	26193	79848	Jeune Asphyxiating Thoracic Dystrophy; Joubert syndrome 21	AR	N/A	N/A	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Mild sensorineural hearing loss has been described in several individuals	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24360803; 24360807; 24360808
CSRP3	2472	8048	Cardiomyopathy, familial hypertrophic 12; Cardiomyopathy, dilated, 1M	AD	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular	There is a wide range of age at presentation	Surveillance for manifestations (including with electrocardiogram and echocardiogram), including in asymptomatic individuals, is recommended; For individuals with cardiomyopathy, treatment such as medical therapy, pacemakers, and ICD can decrease morbidity and mortality, and early recognition and treatment can improve outcomes, though some individuals with progressive/refractory disease may require cardiac transplantation 	12507422; 14567970; 12642359; 18505755; 20087448; 22429680 
CST3	2475	1471	Cerebral amyloid angiopathy	AD	N/A	N/A	Cardiovascular; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4655034; 3495457; 2900981; 11760381; 16612982; 18566660
CSTA	2481	1475	Exfoliative ichthyosis, autosomal recessive, ichthyosis bullosa of Siemens-like	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21944047
CSTB	2482	1476	Myoclonic epilepsy of Unverricht and Lundborg	AR	N/A	N/A	Neurologic	General	Some medications (reports include valproate, N-acetylcysteine, levetiracetam) can result in marked improvement, but phenytoin can worsen neurologic manifestations, and can even increase cerebellar degeneration; Other medications (eg, carbamazepine, oxcarbazepine, tiagabine, vigabatrin, gabapentin,  pregabalin) can worsen myoclonus/myoclonic seizures 	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6137660; 8596935; 9012407; 9054946; 9126745; 9090386; 9527146; 9529356; 9814834; 9932979; 12427904; 12707458; 15508934; 15778103; 18325013; 20301321; 20593193
CTC1	26169	80169	Cerebroretinal microangiopathy with calcifications and cysts	AR	N/A	N/A	Cardiovascular; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3402627; 8628470; 15002047; 15079028; 16943371; 18076099; 21523908; 22267198; 22387016
CTCF	13723	10664	Mental retardation, autosomal dominant, 21	AD	N/A	N/A	Neurologic	General	One described individual had multiple congenital anomalies in addition to neurologic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23746550
CTDP1	2498	9150	Congenital cataracts, facial dysmorphism, and neuropathy	AR	Pediatric		Cardiovascular; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Endocrine; Pharmacogenomic; Renal		Individuals may have hypogonadotropic hypogonadism, and medical management (hormone replacement) may be beneficial to prevent osteoporosis; In the instance of anesthesia, monitoring is indicated, (eg, for severe complications such as stridor, pulmonary edema, malignant hyperthermia, and seizures); Individuals may suffer severe rhabdomyolysis related to viral infections, and awareness may allow rapid management	10439962; 10360766; 10442556; 14517542; 16194727; 16939648; 20301787; 21824574 
CTH	2501	1491	Cystathioninuria	AR	N/A	N/A	Biochemical	General	It is unclear if the condition causes clinical manifestations other than biochemical abnormalities, and medical management (eg, with pyridoxine) may improve the biochemical parameters, though it is unclear if possibly coincident clinical findings are also affected	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14399948; 5637757; 12574942; 20584029
CTHRC1	18831	115908	Barrett esophagus/Esophageal adenocarcinoma	AD	Adult		Gastrointestinal; Oncologic	Gastrointestinal; Oncologic		Awareness of disease risk may allow surveillance, preventive measures (eg, related to Barrett esophagus) and early treatment of malignancy, which may reduce morbidity and mortality	21791690
CTLA4	2505	1493	Autoimmune lymphoproliferative syndrome, type V	AD	Pediatric		Allergy/Immunology/Infectious; Hematologic; Oncologic; Renal	Allergy/Immunology/Infectious; Oncologic		Medical treatment (with immunosuppression) has been described as beneficial; The condition may involve frequent infections, and awareness may allow preventive measures and early and aggressive treatment of infections	25213377; 25329329
CTNNA1	2509	1495	Hereditary diffuse gastric cancer, familial	AD	Adult		Oncologic	Oncologic		Awareness of disease risk may allow surveillance for and early treatment of neoplastic disease, which may reduce morbidity and mortality	23208944
CTNNA3	2511	29119	Arrhythmogenic right ventricular dysplasia, familial, 13	AD	Pediatric		Cardiovascular	Cardiovascular		Individuals have been described as presenting with arrhthymias and echocardiographic findings including right ventricular dilatation and dyskinesia, and awareness can allow surveillance (eg, with echocardiogram, electrocardiogram) and preventive measures and early treatment (eg ,with ICD)	23136403
CTNNB1	2514	1499	Mental retardation, autosomal dominant 19	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23033978; 24614104
CTNS	2518	1497	Cystinosis	AR	Pediatric		Biochemical; Endocrine; Musculoskeletal; Ophthalmologic; Renal	Biochemical; Endocrine; Ophthalmologic; Renal		Cystine-depleting agents (cysteamine) instituted at an early age can be beneficial related to  manifestations affecting multiple organ systems, perhaps including cognitive development, as well as  renal manifestations (renal tubular Fanconi syndrome and glomerular damage), though renal transplantation may be necessary; Surveillance for renal manifestations and related sequelae can allow early detection and management of disease with (in addition to cystine-depleting agents), replacement of renal losses; Dietary management (eg, ensuring sufficient caloric intake, and with vitamin D and phosphate supplementation) can be beneficial related to potential failure to thrive and hypophosphatemic rickets; Cysteamine eyedrops can be beneficial related to ophthalmologic sequelae; Surveillance for endocrine manifestations (eg, hypothyroidism, or hypogonadism in males) can allow early detection and medical management, including potential use of growth hormone in order to optimize height in some individuals	6038997; 4914142; 5443335; 406375; 333912; 7112129; 3307383; 3335962; 3550461; 3674101; 3821824; 3335962; 3185663; 3292915; 381441; 2230837; 552398; 8455682; 8172256; 7593434; 9537412; 10556299; 10417278; 10444339; 10625078; 11001803; 10673275; 12110740; 12442267; 16603246; 17643777; 19863563; 20301574; 20803298; 20814825; 21305353; 21784456; 21868618; 21371554; 21900880; 22903658; 23001048; 23462307; 23538568; 25165189
CTPS1	2519	1503	Immunodeficiency 24	AR	Pediatric		Allergy/Immunology/Infectious; Oncologic	Allergy/Immunology/Infectious; Oncologic		Individuals are susceptible to frequent and severe viral and bacterial infections (as well as sequelae such as EBV-related lymphoma), and and antiinfectious prophylaxis and early and aggressive treatment of infections, as well as awareness of potential oncologic sequelae, may be beneficial; HSCT has been described	24870241
CTSA	9251	5476	Galactosialidosis	AR	Pediatric		Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Biochemical		Cardiac manifestations (eg, valvular anomalies and insufficiency) can be severe, and surveillance (eg, with echocardiogram) may allow early detection of sequalae and treatment; Cytopenias have been described; Renal transplanation has been described as beneficial	4999185; 3149149; 2148053; 8514852; 7759227; 8725271; 8968752; 9762607; 10944848; 18937050 
CTSC	2528	1075	Haim-Munk syndrome; Papillon-Lefevre syndrome; Periodontitis 1, juvenile	AR	Pediatric		Allergy/Immunology/Infectious; Dental; Dermatologic	Allergy/Immunology/Infectious		Early diagnosis to allow control of oral infections can preserve dentition	14244097; 14252683; 162525; 2943312; 2965550; 7623262; 9085215; 10593994; 10581027; 11106356; 10662807; 12509601; 12637913; 14974080; 15606524; 18945301; 19816003; 20359428; 21393975 
CTSD	2529	1509	Ceroid lipofuscinosis, neuronal, 10	AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16670177; 16685649
CTSF	2531	8722	Neuronal ceroid lipofuscinosis 13	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20301601; 23297359
CTSK	2536	1513	Pycnodysostosis	AR	N/A	N/A	Biochemical; Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14041831; 14470123; 1611757; 8703060; 9529353; 10074491; 15070910; 17397052; 19674475; 20305575; 21099701
CUBN	2548	8029	Megaloblastic anemia-1, Finnish type	AR	Pediatric		Gastrointestinal; Hematologic; Renal	Gastrointestinal		Early diagnosis is beneficial, as  early detection may allow life-long medical treatment with parenteral hydroxocobalamin, which can ameliorate morbidity and mortality 	15024727; 22854512; 22929189  
CUL3	2553	8452	Pseudohypoaldosteronism, type IIE	AD	Pediatric		Renal	Renal		Treatment (eg, correction of physiologic abnormalities by thiazide diuretics) can be effective	22266938
CUL4B	2555	8450	Mental retardation, X-linked, syndromic 15	XL	N/A	N/A	Craniofacial; Endocrine; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8135271; 10978355; 17236139; 17273978; 19377476; 20002452; 20014135 
CUL7	21024	9820	Three M syndrome 1; Yakut short stature syndrome	AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16142236; 17675530; 19225462; 21166787; 22624670; 22974575 
CWF19L1	25613	55280	Spinocerebellar ataxia, autosomal recessive 17	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15981765; 25361784
CXCR4	2561	7852	Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM syndrome)	AD	Pediatric		Allergy/Immunology/Infectious; Dermatologic	Allergy/Immunology/Infectious	Because of HPV infections, the condition may include oncologic manifestations	Individuals can be susceptible to a number of types of infections, and prophylaxis (eg, including HPV vaccine) and early and aggressive treatment of infections can be beneficial	889707; 2239986; 10767001; 12692554
CYB5A	2570	1528	46, XY disorder of sex development; Methemoglobinemia, type IV 	AR	Pediatric		Endocrine; Hematologic; Oncologic; Genitourinary	Endocrine; Oncologic; Genitourinary		Hormonal treatment (eg, with estrogen or testosterone) may be beneficial related to sexual characteristics; Due to risk of gonadal tumors, surgical removal may be indicated	3951505; 8168836; 22170710 
CYB5R3	2873	1727	Methemoglobinemia due to methemoglobin reductase deficiency	AR	Pediatric		Biochemical; Hematologic; Neurologic	Biochemical; Pharmacogenomic		Some forms of disease are responsive to medical therapy (eg, with ascorbic acid), though neurological manifestations in severe forms have not been described as being impacted by this type of management; In treatment with certain medications (eg, Dapsone), genotyping may assist in the prevention and/or early treatment of adverse reactions	21011935; 18861684; 1207738; 4063522; 3539237; 1707593; 8427971; 7668255; 7718898; 9266404; 9695975; 10874300; 12803131; 15921385; 15390276; 17964195; 18202104; 18343696; 18820099; 18318771; 19579085; 19997042; 21328435; 22627575;  22658170; 22797852
CYBA	2577	1535	Chronic granulomatous disease, autosomal, due to deficiency of CYBA	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Surveillance for infections and infectious complications is indicated, and preventive measures (eg, antibacterial/antifungal prophylaxis, interferon gamma) may be beneficial; To treat fungal infections, specific antifungal drugs may be beneficial, and longer treatment courses (as well as specific considerations including coadministration with corticosteroids) may be indicated in individuals with CGD; In some instances, HSCT may be beneficial; Certain agents should be avoided, including material that would allow fungal spore inhalation	4384563; 2770793; 3368442; 2713485; 2243141; 1415254; 11060536; 12073015; 18422995; 10759707; 20407811; 22336310; 22562447; 22876374; 22924696; 23910690
CYBB	2578	1536	Chronic granulomatous disease, X-linked; Immunodeficiency 34	XL	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		In Immunodeficiency 34, BCG vacine should be avoided, and recognition may allow prompt diagnosis and treatment of infectious manifestations; In Chronic granulomatous disease, X-linked, surveillance for infections and infectious complications is indicated, and preventive measures (eg, antibacterial/antifungal prophylaxis, interferon gamma) may be beneficial; To treat fungal infections, specific antifungal drugs may be beneficial, and longer treatment courses (as well as specific considerations including coadministration with corticosteroids) may be indicated in individuals with CGD; In some instances, HSCT may be beneficial; Certain agents should be avoided, including material that would allow fungal spore inhalation	13430573; 13636694; 14258653; 4163887; 6021213; 4191616; 7273485; 6851217; 3011845; 2556453; 1710153; 8807090; 9454688; 9888386; 10914676; 11060536; 11259721; 11138621; 12802027; 17544093; 18762975; 21278736; 22236433; 22876374; 22924737; 23193493; 23826567; 23827747; 23859418; 23910690
CYC1	2579	1537	Mitochondrial complex III deficiency, nuclear type	AR	Pediatric		Biochemical	Biochemical		Individuals may present with episodes of acute metabolic decompensation, including hyperlactatemia, hyperammonemia, ketoacidosis and glucose instability, and awareness may allow rapid treatment, including with IV rehydration (and insulin therapy as required), as well as other biochemical interventions (eg, arginine and sodium benzoate)	23910460
CYCS	19986	54205	Thrombocytopenia 4	AD	N/A	N/A	Hematologic	General		Reported clinical findings related to thrombocytopenia were absent or mild; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18345000; 22102269
CYLD	2584	1540	Spiegler-Brooke syndrome; Trichoepithelioma, multiple familial, 1; Cylindromatosis, familial	AD	Pediatric		Dermatologic; Oncologic	Dermatologic; Oncologic		The condition can include a number of types of cancerous lesions for which surveillance/treatment (including surgical management) may be beneficial; In familial trichoepithelioma, skin lesions can degenerate into basal cell carcinoma; In Cylindromatosis, familial, childhood tumors have been reported, and neoplasms may undergo malignant transformation; Individuals are at risk of salivary/parotid adenocarcinoma	8436650; 7684205;  10835629; 11703297; 12190880; 14632188; 12950348; 15854031; 16307661; 16922728; 18234730; 19076795; 19807742; 19917957; 20151946; 20972631; 21712687; 22049921; 22588548; 22689134; 22296260; 22882113; 23249834; 23260808; 23567228; 23694822
CYP11A1	2590	1583	Adrenal insufficiency, congenital, with 46,XY sex reversal, partial or complete	AD/AR	Pediatric		Endocrine; Oncologic; Genitourinary	Endocrine; Oncologic; Genitourinary		Presentation of classic enzymatic deficiency involves adrenal failure and salt wasting in infancy, which can be treatable; Nonclassic forms may present later with some retained adrenal function and abnormal sexual development; Surgical interventions may decrease the risk of gonadal tumors 	11502818; 12161514; 15507506; 16705068; 18182448; 21159840
CYP11B1	2591	1584	Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency; Glucocorticoid-remediable aldosteronism	AD/AR	Pediatric		Endocrine; Oncologic; Genitourinary	Endocrine; Oncologic; Genitourinary	Glucocorticoid-remediable aldosteronism involves a fusion gene (with CYP11B2)	In adrenal hyperplasia, treatment of manifestations such as hypertension (fatal vascular accidents have been reported in individuals with relatively mild virilization) and hypokalemia, as well as genitourinary anomalies, can be beneficial; Screening for oncologic complications (eg, testicular adrenal rest tumors) can allow early detection and treatment; In Glucocorticoid-remediable aldosteronism, medical treatment (eg, with glucocorticoids) can be beneficial	13345203; 7355668; 7026592; 6268979; 7049883; 3875277; 2022736; 1430088; 17172090; 1731223; 1472060; 1554023; 7670248; 7550315; 8825044; 8768848; 10689646; 10566645; 10999827; 10852446; 11549669; 12107222; 16551734; 20980225; 22508345; 22790459; 23057653; 23146819; 23291679; 23345044; 23441661; 23940125; 24022297
CYP11B2	2592	1585	Corticosterone methyloxidase type I deficiency; Corticosterone methyloxidase type II deficiency;  Glucocorticoid-remediable aldosteronism	AD/AR	Pediatric		Endocrine; Genitourinary; Oncologic	Endocrine; Genitourinary; Oncologic	Glucocorticoid-remediable aldosteronism involves a fusion gene (with CYP11B1)	In Corticosterone methyloxidase, treatment of salt wasting (eg, with salt/mineralocorticoid supplementation) has shown success; In Glucocorticoid-remediable aldosteronism, medical treatment (eg, with glucocorticoids) can be beneficial; Surgical interventions may decrease the risk of gonadal tumors 	14212087; 14250395; 295679; 4121586; 838841; 6268979; 2044581; 1731223; 1472060; 1601005; 1594605; 8439335; 7550315; 8825044; 9360501; 9814506; 10566645; 10999827; 10852446; 11238478; 12107222; 18178501; 19116236; 20494601; 22465514 
CYP17A1	2593	1586	Adrenal hyperplasia, congenital, due to 17-alpha-hydroxylase deficiency	AR	Pediatric		Endocrine;Genitourinary;  Oncologic	Endocrine; Genitourinary; Oncologic		Individuals may not necessarily manifest with adrenal crisis, but mineralocorticoid excess may result in severe hypokalaemic hypertension, and awareness may allow preventive measures and treatment (eg, including glucocorticoids and mineralcorticoid antagonists); Treatment of genitourinary anomalies, as well as related hypogonadotrophic hypogonadism (eg, with hormone replacement therapy, as well as surgery in some individuals), can be beneficial; Due to risk of malignancy, gonadectomy may be indicated in genotypic males	4288776; 6039879; 4303304; 5456802; 999330; 6976525; 2843762; 2026124; 1648117; 2808364; 7629254; 8855840; 9360545; 9326943; 9177409; 11549685; 14671162; 16121340; 18559916; 20170344; 21823532; 22452398; 21550081; 22954317 
CYP19A1	2594	1588	Aromatase deficiency	AR	Pediatric	Allelic with Aromatase excess syndrome (AD), in which medical treatment (eg, with aromatase inhibitors) can be beneficial, but it is unclear if early (genetic) diagnosis would be advantageous	Endocrine	Endocrine		Females may present with virilization resulting in manifestations such as pseudohermaphroditism , while males may present later with manifestations such as delayed skeletal maturation and epiphyseal closure, skeletal pain, eunuchoid habitus and increased adiposity, and  estrogen therapy reverses symptoms	1825497; 8265607; 9543166; 12736278; 15811932; 17452968; 21521281; 21470988 
CYP1A2	2596	1544	CYP1A2-related drug metabolism	AD	Pediatric		General	Pharmacogenomic		Variants may also be related to subclinical metabolism of a number of agents (including medications), as well as related as a susceptibility factor; Porphyria cutanea tarda, severity of refersto a susceptibility locus and/or evidence or clinical applicability unclear	8035341; 10101295; 10233211; 10376760; 11153915; 12172216; 16522833; 17971810; 20881513; 20955109; 20147896; 19636338; 21121774; 19682433; 21989077
CYP1B1	2597	1545	Glaucoma, primary open angle, adult-onset; Peters anomaly; Glaucoma 3A, primary congenital; Glaucoma, primary open angle glaucoma, juvenile-onset 	AR	Pediatric		Ophthalmologic	Ophthalmologic; Pharmacogenomic	Severe and difficult to treat glaucoma has been reported in many individuals with Peters anomaly; heterozygous variants may increase susceptibility to glaucoma; Digenic inheritance (with MYOC) has been reported; Variants may also act as disease modifiers (eg, related to Glaucoma, age of onset)	Early diagnosis and treatment with surgery (with the use of pre and postoperative agents to control intraocular pressure), or, if surgery is not effective, drainage implants or cyclodestruction, may be effective to decrease morbidity and mortality related to vision loss; Agents that may contribute to glaucoma, as well as alpha-2-agonists, should be avoided	9097971; 9463332; 9497261; 10227395; 10655546; 11730663; 11403040; 12372064; 11774072; 15342693; 15733270; 17718864; 19807744; 19643970; 20301314; 21081970; 21600657; 22128238; 22942166; 23218701; 23363883; 24227805
CYP21A2	2600	1589	Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency; Hyperandrogenism, nonclassic type, due to 21-hydroxylase deficiency	AR	Pediatric		Cardiovascular; Endocrine; Genitourinary; Oncologic	Cardiovascular; Endocrine; Genitourinary; Oncologic		In classic 21-OHD CAH, medical therapy (with glucocorticoid replacement), including with stress dosing glucocorticoid replacement therapy is beneficial; In the salt-wasting form, medical therapy (eg, with mineralocorticoid therapy, sodium chloride) can be beneficial; Surveillance and early treatment for neoplasms such as testicular adrenal rest tumors is indicated, as is surveillance related to multiple factors such as BMI, bone mineral density, fertility, and cardiovascular risk factors	13968788; 4298539; 835605; 152409; 6449518; 6102330; 317470; 6095106; 2989686; 3030300; 3491959; 3038528; 2667968; 2783976; 2247119; 1311000; 1644925; 7957400; 8855797; 8626833; 8923864; 9360525; 9329356; 9100612; 8989258; 9851787; 9661649; 9613359; 9829208; 10372672; 10084573; 10199755; 10720040; 11070100; 0720048; 11397874; 11232002; 11397897; 11739428; 12107196; 12213842; 12183722; 12788866; 12930931; 12915679; 12843131; 14764770; 16926248; 17299071; 17878254; 17535996; 17148562; 17456574; 8989258; 18381579; 20392211; 20301350; 22841790; 23073904; 22157069; 22241917; 22802425; 23044877; 22186144
CYP24A1	2602	1591	1,25(OH)(2)D-24-hydroxylase deficiency 	AR	Pediatric		Endocrine; Renal	Endocrine; Renal		Individuals may present early in life with  typical hypercalcemic signs/symptoms (eg, failure to thrive,dehydration, and muscular hypotonia or lethargy), or may present later with nephrolithiasis and nephrocalcinosis, and dietary measures, including avoidance of certain vitamin supplements (eg, vitamin D-containing compounds) to avoid hypercalcemia can be beneficial	3490596; 21675912; 22047572; 23293122 
CYP26C1	20577	340665	Focal facial dermal dysplasia 4	AR	N/A	N/A	Craniofacial; Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16530710; 23161670 
CYP27A1	2605	1593	Cerebrotendinous xanthomatosis	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	Biochemical; Cardiovascular		The condition manifests with progressive neurologic dysfunction, as well as cardiovascular and ophthalmologic dysfunction, and medical treatment (eg, with chenodeoxycholic acid and HMG-CoA reductase inhibitors) can be beneficial	5636664; 5676919; 5355255; 4825231; 7315872; 7298854; 6504105; 3106810; 3128689; 1708392; 7847220; 7964884; 10430841; 11804206; 12555943; 11939886; 16278884; 18227423; 20301583; 20402754; 20450308; 20558929; 21553098; 22018287; 22336472; 23375591 
CYP27B1	2606	1594	Vitamin D-dependent rickets, type 1A	AR	Pediatric		Endocrine	Endocrine		Medical treatment with forms of vitamin D can be effective for prevention and treatment of manifestations, such as skeletal anomalies and seizures	6265615; 9486994
CYP2A6	2610	1548	CYP2A6-related drug metabolism	AD	Pediatric		General	Pharmacogenomic		Selection and dosing of medications may be affected by the presence of variants	2322567; 9409631; 9827545; 10093988; 12042667; 12325023; 19238117; 23089672 
CYP2B6	2615	1555	Efavirenz, poor metabolism of	AD	Pediatric		General	Pharmacogenomic		It has been suggested that CYP2B6 genotype should be considered in efavirenz treatment	15622315; 20639527; 20860463; 23080225; 23152403 
CYP2C19	2621	1557	Drug metabolism, CYP2C19-related	AD	Pediatric		General	Pharmacogenomic		Selection and dosing of medications (eg, aspirin, clopidogrel, escitalopram, imipramine, omeprazole, tamoxifen) may be affected by the presence of variants	6489416; 3739364; 1302040; 8195181; 9093256; 16413245; 18004210; 18024866; 17625515; 19706858; 19106083; 19193675; 20083681; 20223877; 20978260; 20979470; 21047200; 19884907; 20351750; 20492469; 20801498; 20826260; 21178986; 21262992; 21288102; 21392617; 21288105; 21358751; 21700758; 21716271; 21716274; 21854540; 22027650; 22088980; 22228204; 22462746; 23090703; 23089672 
CYP2C8	2622	1558	Rhabdomyolysis, cerivastatin-induced	AR	Pediatric		General	Pharmacogenomic		An individual with homozygosity for a frameshift mutation developed acute rhabdomyolysis after cervistatin treatment; Patients with homozygous/compound heterozygous mutations may be at risk for complications from medications including statins	15365880
CYP2C9	2623	1559	Drug metabolism, CYP2C9-related	AD	Pediatric		General	Pharmacogenomic		Selection and dosing of medications may be affected by the presence of variants	10073515; 10901705; 19228618; 19300499; 19715737; 19794412; 20089352; 20402581; 21562147; 23089672 
CYP2D6	2625	1565	Drug metabolism, CYP2CD6-related	AD	Pediatric		General	Pharmacogenomic		Variants may affect the metabolism of mulitple drugs including debrosoquine, sparteine, nortriptyline,  codeine, tamoxifen	4082245; 1978251; 1673290; 8093319; 7903454; 9012401; 11940091; 15625333; 19809024 ; 22406651; 22733239; 22775532 
CYP2R1	20580	120227	Vitamin D hydroxylation deficient rickets, type 1B	AR	Pediatric		Endocrine	Endocrine		Medical treatment (eg, with supraphysiological levels of vitamin D3 or D2) has been reported to result in improvement or resolution of biochemical and clinical/radiographic anomalies	8201479; 15128933; 22855339
CYP2U1	20582	113612	Spastic paraplegia 56, autosomal recessive	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23176821
CYP3A4	2637	1576	Drug metabolism, CYP3A4-related	AD	Pediatric		General	Pharmacogenomic		Selection and dosing of medications (eg,colchicine) may be affected by the presence of variants	9789061; 18973929; 19337788; 19802823; 19907160; 20386561; 21047202; 20437462; 20440227; 21902501; 21902502; 21903774; 21946898 
CYP3A5	2638	1577	Drug metabolism, CYP3A5-related	AD	Pediatric		General	Pharmacogenomic		Selection and dosing of many medications may be affected by the presence of variants	11740341; 15284534; 12065767; 20212519; 21412232; 22015057; 22210422; 22304537; 22407409; 22706623; 22875663; 23033116 
CYP4F2	2645	8529	Warfarin metabolism	AD	Pediatric		General	Pharmacogenomic		Selection and dosing of medications (warfarin) may be affected by the presence of variants	18250228; 19207028; 19300499; 22417713; 22534826; 22854539; 22855976 
CYP4F22	26820	126410	Ichthyosis, congenital, autosomal recessive 5	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16436457
CYP4V2	23198	285440	Bietti crystalline corneoretinal dystrophy; Retinitis pigmentosa, autosomal recessive	AR	N/A	N/A	Ophthalmologic	General	Subclinical manifestations have been described in heterozygous individuals	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5299874; 306693; 3493804; 2783846; 11001583; 15042513; 18398705; 19508456; 21385027; 21565171;  22087103; 22497028; 22605929; 22693542; 22772592; 23143451; 23221965; 23242590; 23538635
CYP7B1	2652	9420	Bile acid synthesis defect, congenital, 3	AR	Pediatric	Allelic with Spastic paraplegia 5A (AR)	Gastrointestinal; Neurologic	Gastrointestinal		Individuals may manifest with early-onset, progressive and severe cholestatic liver disease, and early recognition may allow treatment; Liver transplanation has been described	7987300; 9802883; 18252231; 19187859; 19439420; 21567895; 21623769; 22384504 
CYTB	7427	4519	Myoglobinuria, recurrent; Leber hereditary optic neuropathy; Cardiomyopathy, infantile histiocytoid	Maternal	N/A	N/A	Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6093033; 1732158; 1764087; 9894887; 10502593; 10960495
D2HGDH	28358	728294	D-2-hydroxyglutaric aciduria	AR	N/A	N/A	Biochemical; Cardiovascular; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15609246; 19169842; 20020533
DAG1	2666	1605	Muscular dystrophy-dystroglycanopathy, type C, 9	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14678799; 21388311
DARS2	25538	55157	Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15326244; 17384640; 19592391; 21749991; 21815884; 22677571; 23065766; 23644316
DBH	2689	1621	Dopamine beta-hydroxylase deficiency	AR	Pediatric		Biochemical; Genitourinary; Neurologic; Ophthalmologic; Renal	Biochemical; Renal		Medical therapy (eg, droxidopa) can effectively treat manifestations such as orthostatic hypotension; Surveillance of renal function should be instituted; For untreated individuals, circumstances such as vigorous exercise, hot environements, and dehydration should be avoided; In infantile-onset disease, awareness of hypotension, hypothermia, and hypoglycemia may be beneficial	3010116; 2890806; 2880016; 2300263; 2217667; 9651662; 16722595; 1677640; 11857564; 20063034; 20301647; 21471955 
DBT	2698	1629	Maple syrup urine disease, type II	AR	Pediatric		Biochemical; Neurologic	Biochemical		Dietary measures (eg, leucine restriction, high-calorie branched chain amino acid-free formulas, isoleucine and valine supplementation) combined with careful surveillance can be beneficial to prevent decompensation and minimize disease sequelae; Specific treatment in times of metabolic decompensation can reduce morbidity and mortaility; Liver transplantation is effective for classic MSUD; Specific monitoring is indicated in pregnancy	1847055; 1990841; 9621512; 11112664; 14517957; 14567968; 16786533; 20301495; 20946191; 22727569; 23313820
DCAF17	25784	80067	Woodhouse-Sakati syndrome	AR	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Endocrine; Neurologic	Cardiovascular; Endocrine		Endocrine anomalies can include hypothyroidism and hypogonadism, and surveillance to allow appropriate medical care  (eg, with replacement therapy, as well as care for manifestations such as diabetes mellitus)  may be beneficial; Cardiac anomalies (including arrhythmia) have been reported, and surveillance and preventive measures may be beneficial; Awareness of hearing impairment may allow early interventions related to speech and language development	6876115; 7710875; 19026396; 18049083; 18175354; 20507343; 21963443; 21964978
DCAF8	24891	50717	Giant axonal neuropathy 2, autosomal dominant	AD	Adult		Cardiovascular; Neurologic	Cardiovascular		Individuals have been described with cardiomyopathy, and awareness may allow early management	3859241; 24500646
DCC	2701	1630	Mirror movements 1	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19127048; 19720981; 20431009; 21242494
DCLRE1C	17642	64421	Omenn syndrome; Severe combined immunodeficiency with sensitivity to ionizing radiation	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal	Allergy/Immunology/Infectious		Individuals typically present early in life with sequelae of infections, which are typically frequent and can be severe, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT may be beneficial	12055248; 12569164; 15731174; 19912631; 21184155 
DCN	2705	1634	Corneal dystrophy, congenital stromal	AD	Adult		Ophthalmologic	Ophthalmologic		In addition to other ophthalmologic care that may be effective (eg, penetrating keratoplasty), open-angle glaucoma has been described in several individuals, and awareness of this risk may allow surveillance and early treatment	5304426; 15671264; 16935612; 20301741; 21993463; 24413633
DCTN1	2711	1639	Neuropathy, distal hereditary motor, type VIIB; Perry syndrome	AD	N/A	N/A	Neurologic; Pulmonary	Neurologic; Pulmonary		In Perry syndrome, individuals may manifest with severe and potentially lethal hypoventilation, and interventions including aggressive pulmonary as well as medical management (eg, carbidopa/levodopa) may be beneficial	1122173; 43704; 3352925; 2247238; 11940687; 12627231; 15326253; 19136952; 20437543; 20702129; 20945553; 24343258
DCX	2714	1641	Lissencephaly, X-linked, 1; Subcortical laminal heteropia, X-linked 	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9489699; 9489700; 9817918; 10430413; 10915612; 11175293; 12034802; 12552055; 19673952; 19050731; 19619967; 19673952; 20301364; 20726879; 21488284; 22408144; 25140959
DCXR	18985	51181	Pentosuria	AR	N/A	N/A	Biochemical	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22042873
DDB2	2718	1643	Xeroderma pigmentosum, group E	AR	Pediatric		Dermatologic; Oncologic; Ophthalmologic	Dermatologic; Oncologic		Skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance (primarily related to skin manifestations, as well as other sequelae) can be beneficial	3175673; 3339259; 8798680; 10447254; 20301571
DDC	2719	1644	Aromatic l-amino acid decarboxylase deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		Medical treatment (eg, with MAOI, dopamine agonists, and pyridoxine) has been reported as resulting in clinical improvement in some patients, largely with a milder form of disease, though functional clinical outcomes may be poor in many individuals	1700191; 1357595; 9309516; 12891654; 15079002; 20505134; 21963339 
DDHD2	29106	23259	Spastic paraplegia 54	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16636240; 23176823; 24482476
DDOST	2728	1650	Congenital disorder of glycosylation, type Ir	AR	Pediatric		Biochemical; Gastrointestinal; Neurologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	22305527
DDR2	2731	4921	Spondylometaepiphyseal dysplasia, short limb-hand type	AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8434618; 19110212; 20223752 
DDX11	2736	1663	Warsaw breakage syndrome	AR	N/A	N/A	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	General	The condition can involve multiple congenital anomalies; It has been suggested that heterozygotes (and, presumably, homozygotes) may be at increased risk of malignancies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20137776; 23033317
DEAF1	14677	10522	Mental retardation, autosomal dominant 24	AD	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21076407; 23020937; 24726472
DECR1	2753	1666	2,4-dienoyl-CoA reductase deficiency	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2332510
DEPDC5	18423	9681	Epilepsy, familial focal, with variable foci	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9851433; 10577924; 14510823; 15329069; 22780917; 23542697; 23542701; 24814846
DES	2770	1674	Myopathy, myofibrillar 1; Cardiomyopathy, dilated, 1I	AD/AR	Pediatric	Allelic with Scapuloperoneal syndrome, neurogenic, Kaeser type (AD)	Cardiovascular; Musculoskeletal; Neurologic	Cardiovascular		In myofibrillar myopathy, individuals typically present with slowly progressive weakness, and a significant proportion of individuals demonstrate cardiomyopathy, such that surveillance for arrhythmia or conduction defects may allow early treatment (eg, pacemaker, ICD); Cardiac transplantation may be necessary in individuals with severe forms of cardiomyopathy; In dilated cardiomyopathy, surveillance (eg, with electrocardiogram and echocardiogram) can allow early detection and interventions (including medications) in order to ameliorate morbidity and mortality	5828910; 8114783; 7672786; 9697706; 9736733;  10430757; 10545598; 11073539; 17221859; 17439987; 19433360; 19879535; 20301672; 20664348; 20718792; 22215463; 24200904
DFNA5	2810	1687	Deafness, autosomal dominant 5	AD	N/A	N/A	Audiologic/Otolaryngologic	General	The onset of deafness has been described as postlingual	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5919633; 5919636; 9771715; 12126021; 12408063; 14559215; 14676472; 17868390; 17427029; 17868390; 19911014; 21805831 
DFNB31	16361	25861	Usher syndrome, type 2D; Deafness, autosomal recessive 31	AR	Pediatric		Audiologic/Otolaryngologic; Ophthalmologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	12833159; 17171570 
DFNB59	29502	494513	Deafness, autosomal recessive 59	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	17718865; 17373699; 7301963; 17329413
DGAT1	2843	8694	Diarrhea 7	AR	Pediatric		Gastrointestinal	Gastrointestinal		Individuals may present in infancy with severe diarrhea, protein-losing enteropathy, metabolic acidosis, and electrolyte disturbances, and preventive measures and early treatment (including TPN) may be beneficial	23114594
DGCR2	2845	9993	Schizophrenia	AD	N/A	N/A	Neurologic	General		Evidence or clinical applicability unclear	21822266
DGKE	2852	8526	Nephrotic syndrome, type 7	AR	Pediatric	N/A	Renal	Renal	Immunosuppressive therapy, as well as medical management (eg, with ACE inhibitors) have been described as beneficial in some individuals, but it is not clear that early (genetic) diagnosis would be beneficial; Renal transplant has been described	In Hemolytic-uremic syndrome, some individuals have been described as responding to medical treatment (eg, immunosuppression, ACE inhibitors), and the choice of specific treatment modalitie, as well as decision to perform renal transplant, may be dictated by genetic diagnosis; Certain agents/precipitating factors should be avoided (eg, certain medications); Renal transplant has been described	23274426; 23542698
DGUOK	2858	1716	Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)	AR	Pediatric		Biochemical; Gastrointestinal; Musculoskeletal; Neurologic 	Gastrointestinal		In individuals with isolated liver disease, liver transplantation  has been described as potentially beneficial, though there has been no reported survival advantage in instances of multisystem illness; Awareness may allow prompt recognition and treatment of manifestations such as neonatal hypoglycemia and hepatic dysfunction	11687800; 12205643; 15883261; 15887277; 16908739; 18205204; 18825706; 20301766; 21534344;  22137549; 22602837; 22622127; 22868686; 23043144; 23141463 
DHCR24	2859	1718	Desmosterolosis	AR	N/A	N/A	Biochemical; Craniofacial; Musculoskeletal; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9450875; 11519011; 12457401; 21559050; 21671375
DHCR7	2860	1717	Smith-Lemli-Opitz syndrome	AR	Pediatric		Biochemical; Cardiovascular; Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Renal	Biochemical	The condition may be recognizable by the constellation of manifestations	Though the data are not definitive, anecdotal reports suggest that cholesterol supplementation and medical treatment (eg, with statins) may be clinically beneficial; Awareness of the potential for multiple malformations (some of which may be occult) may be beneficial to allow prompt recognition and management	14119520; 3812577; 8209913; 7632194; 7684480; 8831138; 8863875; 9024557; 9024564; 9024565; 9024566; 9130950; 9653161; 9683618; 11562938; 9634533; 9683613; 11161831; 10946022; 10951458; 11223857; 11167696; 12366604; 12407710; 15192627; 16761297; 17497248; 20301322; 18285838; 19430384; 20635399; 19365639; 20014133; 23042628; 23072947; 23162303; 23293579; 23319240; 23321614; 23426833; 23532938; 23538569; 23595802; 23688395; 23790112
DHDDS	20603	79947	Retinitis pigmentosa 59	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21295282; 21295283
DHFR	2861	1719	Megaloblastic anemia due to dihydrofolate reductase deficiency	AR	Pediatric		Biochemical; Hematologic; Neurologic	Biochemical		The condition manifests with neurologic sequelae and megaloblastic anemia, and medical management (eg, with folinic acid) may help improve clinical parameters	21310276; 21310277
DHH	2865	50846	46,XY partial gonadal dysgenesis, with minifascicular neuropathy; 46,XY sex reversal 7	AD/AR	Pediatric		Endocrine; Genitourinary; Neurologic; Oncologic	Endocrine; Genitourinary; Oncologic	Heterozygous mutations have been reported associated with mosaic 45,X/46,XY karyotypes	Individuals may be at risk for oncologic processes related to gonadal tumors, and diagnosis and treatment (eg, with surgical removal) may be beneficial	11017805; 15356051; 16390857; 21816240 
DHODH	2867	1723	Miller syndrome; Postaxial acrofacial dysostosis	AR	N/A	N/A	Craniofacial; Musculoskeletal; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	501501; 19915526; 21346561; 22692683 
DHTKD1	23537	55526	Charcot-Marie-Tooth disease, type 2Q; 2-aminoadipic and 2-oxoadipic aciduria	AD/AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic	General	In 2-aminoadipic and 2-oxoadipic aciduria, dietary management (with protein restriction) has been reported, but it is not clear whether this was beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23141293; 23141294
DIABLO	21528	56616	Deafness, autosomal dominant 64	AD	N/A	N/A	Audiologic/Otolaryngologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21722859
DIAPH1	2876	1729	Deafness, autosomal dominant 1	AD	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Onset has been described as prelingual in some individuals, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	7211837; 1350680; 9360932; 22938506 
DIAPH2	2877	1730	Premature ovarian failure 2A	XL	Pediatric		Endocrine; Obstetric	Obstetric	Reported individuals have been affected with cytogenetic imbalances	Genetic knowledge may allow fertility preservation such as by storing eggs	8406446; 9070928; 9497258
DICER1	17098	23405	DICER1 syndrome	AD	Pediatric		Oncologic	Oncologic	Individuals are at risk for multiple malignancy types	As individuals are at risk for a variety of neoplasms, surveillance and early diagnosis allowing early treatment of specific tumor types could potentially be beneficial	6261577; 799599; 9345104; 9295070; 18570301; 19556464; 21036787; 21266384; 21882293; 24761742
DIP2B	29284	57609	Mental retardation, FRA12A type	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4042396; 10955484; 17236128 
DIS3L2	28648	129563	Perlman syndrome	AR	Pediatric		Craniofacial; Musculoskeletal;  Neurologic; Oncologic; Renal	Oncologic	Individuals may be affected by multiple congenital anomalies	Individuals have a high risk of Wilms tumor, and surveillance may allow early detection and treatment, which may be beneficial	4315293; 163679; 6093533; 3024486; 10508986; 22306653; 22705997; 23486540; 23613427
DKC1	2890	1736	Dyskeratosis congenita, X-linked; Hoyeraal-Hreidarsson syndrome	XL	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic;  Oncologic; Pulmonary	Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary		Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; Lung transplant may be indicated in individuals with advanced lung diease; HSCT may be indicated due to manifestations including leukemia and bone marrow failure (which may also be treated with androgen therapy), but the long-term efficacy may not be optimal; Awareness of infectious risk may allow prompt diagnosis and treatment of infections	14096348; 5442429; 768476; 7272212; 6601257; 3009302; 3236366; 3201986; 1958493; 1361371; 1390173; 8318369; 7607282; 9590285; 8616066; 9042917; 9886310; 10583221; 10364516; 10700698; 12406104; 18005359; 18627054; 19415736; 19327580; 21415081; 20301779
DLAT	2896	1737	Pyruvate dehydrogenase E2 deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		Medical treatment (eg, with lipoic acid, thiamine, and ketogenic diet) has been reported as resulting in marked clinical improvement	2112155; 2112155; 20022530; 22896851; 23021068
DLD	2898	1738	Dihydrolipoyl dehydrogenase deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		The potential benefit of long-term medical treatment (eg, with riboflavin, biotin, coenzyme Q and carnitine) has been reported; Biochemical (but not clinical) improvement has been described with high-fat, low-protein diet with MCT oils and sodium dichloroacetate	3769994; 8506365; 8968745; 9298831; 9540846; 9934985; 11687750; 12925875; 14765544; 16770810; 16601893 
DLG3	2902	1741	Mental retardation, X-linked 90	XL	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15185169; 24721225
DLL1	2908	28514	Holoprosencephaly	AD	N/A	N/A	Craniofacial; Endocrine; Neurologic	General	Individuals with holoprosencephaly  may demonstrate endocrine anomalies, including diabetes insipidus	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21196490
DLL3	2909	10683	Spondylocostal dysostosis 1, autosomal recessive	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2805381; 10742114; 12746394; 15200511
DLX3	2916	1747	Trichodontoosseous syndrome; Amelogenesis imperfecta, type IV	AD	N/A	N/A	Craniofacial; Dental; Dermatologic; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9467018; 9783705; 10466415; 15666299; 18203197; 18362318; 18492670; 19608154; 21252474 
DLX5	2918	1749	Split-hand/foot malformation 1 with sensorineural hearing loss	AR	Pediatric		Audiologic/Otolaryngologic; Dental; Musculoskeletal	Audiologic/Otolaryngologic	The condition may be recognizable, but deafness may not be recognized as a component feature	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	22121204
DMD	2928	1756	Duchenne muscular dystrophy; Becker muscular dystrophy; Cardiomyopathy, dilated, 3B	XL	Pediatric		Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	Cardiovascular	Cardiomyopathy is common in individuals, and has been specifically described as an isolated finding in females with mutations	Individuals may present at varying ages and with varying degrees of severity, but due to risk of dilated cardiomyopathy, surveillance for manifestations (including with electrocardiogram and echocardiogram), including in asymptomatic individuals as well as mutation-positive females, is recommended; For individuals with cardiomyopathy, treatment such as medical therapy, pacemakers, and ICD can decrease morbidity and mortality, and early recognition and treatment can improve outcomes, though some individuals with progressive/refractory disease may require cardiac transplantation 	13249581; 6683357; 2879922; 3574369; 3612177; 3384440; 2404210; 2325103; 2180286; 1683155; 1518025; 8232953; 8361506; 7802009; 8198142; 8012195; 8789442; 9611069; 11726549; 9170407; 19367636; 19449031; 19367636; 20301298; 22428906; 22451200; 22609847; 22632414; 22650324; 23092449; 23299919
DMGDH	24475	29958	Dimethylglycine dehydrogenase deficiency	AR	N/A	N/A	Biochemical; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10102904
DMP1	2932	1758	Hypophosphatemic rickets, autosomal recessive 1	AR	Pediatric		Endocrine	Endocrine		Supplementation (eg, with phosphate and vitamin D) can be beneficial  	17033621; 17033625
DMPK	2933	1760	Myotonic dystrophy 1	AD/AR	Pediatric		Cardiovascular; Endocrine; Musculoskeletal; Neurologic	Cardiovascular		Individuals have been reported with fatal arrhythmias prior to other signs and symptoms, and cardiologic surveillance (including with EKG) and preventive measures may be beneficial	1101835; 1167063; 6639233; 1346925; 1310900; 1346924; 1546326; 1346923; 1546325; 1303233; 8353490; 8503448; 8421476; 7696601; 7880334; 8071955; 7473648; 7650805; 8880582; 9106286; 9391889; 10325709; 11071501; 11807903; 15557517; 15596617; 17575483; 17663477; 18565861; 19949042; 19514047; 20018643; 20301344; 21259315; 22643181; 22995693 
DMXL2	2938	23312	Polyendocrine-polyneuropathy syndrome	AR	Pediatric		Endocrine; Neurologic	Endocrine		Among other findings, individuals may manifest with hypothyroidism, early-onset hypoglycemia, and hypogonadotropic hypogonadism, and awareness may allow medical treatment of these endocrine diosrders	25248098
DNA2	2939	1763	Progressive external ophthalmoplegia, autosomal dominant, 6; Seckel syndrome 8	AD/AR	N/A	N/A	Biochemical; Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23352259; 24389050
DNAAF1	30539	123872	Ciliary dyskinesia, primary, 13	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	19944405; 19944400; 20301301 
DNAAF2	20188	55172	Ciliary dyskinesia, primary, 10	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	19052621; 20301301;
DNAAF5	26013	54919	Ciliary dyskinesia, primary, 18	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	20350728; 23040496
DNAH1	2940	25981	Spermatogenic failure	AR	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24360805
DNAH11	2942	8701	Ciliary dyskinesia, primary, 7	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	9585585; 12142464; 18022865; 20301301; 20513915; 22184204; 22499950 
DNAH5	2950	1767	Ciliary dyskinesia, primary, 3, with or without situs inversus	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	11788826; 16627867; 19300264; 19357118; 20301301; 22416021; 22499950
DNAI1	2954	27019	Ciliary dyskinesia, primary, 1	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	10577904; 11231901; 11893720; 16858015; 18434704; 19300264; 20301301; 21143860; 22416021; 22499950 
DNAI2	18744	64446	Ciliary dyskinesia, primary, 9	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	18950741; 20301301; 23261302
DNAJB6	14888	10049	Muscular dystrophy, limb-girdle, type 1E	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22334415; 22366786; 24594375
DNAJC19	30528	131118	3-methylglutaconic aciduria, type V	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Genitourinary; Hematologic; Neurologic; Ophthalmologic	Cardiovascular		Individuals frequently demonstrate findings including cardiac manifestations such as dilated cardiomyopathy and dysrhythmias, and surveillance may allow early detection and management	16055927; 22981120
DNAJC5	16235	80331	Ceroid lipofuscinosis, neuronal 4, Parry type; Kufs disease, autosomal dominant	AD	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5132971; 4414475; 62240; 932739; 11489285; 12112194; 21820099; 22073189; 22235333; 22978711 
DNAJC6	15469	9829	Juvenile Parkinsonism, autosomal recessive	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22563501; 23211418
DNAL1	23247	83544	Ciliary dyskinesia, primary, 16	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	20301301; 21496787
DNAL4	2955	10126	Mirror movements 3	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	25098561
DNASE1L3	2959	1776	Systemic lupus erythematosus 16	AR	N/A	N/A	Allergy/Immunology/Infectious	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22019780
DNM1L	2973	10059	Encephalopathy, lethal, due to defective mitochondrial and peroxisomal fission	AD	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17460227
DNM2	2974	1785	Charcot-Marie-Tooth disease, dominant intermediate B; Charcot-Marie-Tooth disease, axonal, type 2M; Myopathy, centronuclear; Lethal akinesia and musculoskeletal abnormalities, with brain and retinal hemorrhages, autosomal recessive	AD/AR	N/A	N/A	Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	General	Neutropenia has been described in several individuals	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11533912; 12481986; 12761657; 16227997; 15731758; 17932957; 18560793; 19122038; 20817456; 21221624; 22091729; 22396310; 22613877; 22924779; 23092955 
DNMT1	2976	1786	Neuropathy, hereditary sensory, type IE; Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant	AD	N/A	N/A	Audiologic/Otolaryngologic; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7898717; 10210919; 21532572; 22328086; 22338191 
DNMT3A	2978	1788	Tatton-Brown-Rahman syndrome	AD	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24614070
DNMT3B	2979	1789	Immunodeficiency-centromeric instability-facial anomalies syndrome 1	AR	Pediatric		Allergy/Immunology/Infectious; Neurologic 	Allergy/Immunology/Infectious		Though the disorder may be clinically recognizable in many individuals, immunoglobulin supplementation can be beneficial, as can prophylaxis and early and aggressive treatment of infections 	8076938; 10555141; 10647011; 11102980; 17893117
DOCK6	19189	57572	Adams-Oliver syndrome 2	AR	N/A	N/A	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3354597; 21820096; 25132448
DOCK7	19190	85440	Epilepitic encephalopathy, early infantile, 23	AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24814191
DOCK8	19191	81704	Hyper-IgE recurrent infection syndrome, autosomal recessive	AR	Pediatric	Allelic with Mental retardation, autosomal dominant 2 (AD)	Allergy/Immunology/Infectious; Neurologic; Oncologic	Allergy/Immunology/Infectious; Oncologic		Antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial; Individuals may also be at higher risk of oncologic complications, including lymphoma and squamous cell carcinomas,  and awareness and surveillance may be beneficial in order to allow early detection and treatment; HSCT has been described	2338345; 14722525; 18060736; 18337720; 19776401; 23891736; 24104410; 24106060
DOK7	26594	285489	Myasthenia, limb-girdle, familial	AR	Pediatric	Allelic with Fetal akinesia deformation sequence (AR)	Musculoskeletal; Neurologic	Musculoskeletal; Neurologic; Pharmacogenomic		Unlike individuals with other types of genetic myasthenia, individuals with DOK7 mutations typically do not respond to chronic AChE inhibitor treatment, but other therapies (eg,  albuterol, ephedrine, salbutamol) treatment has been reported to result in marked clinical improvement; Agents that affect neuromuscular transmission and exacerbate myasthenic manifestations should be avoided; Additional neurologic monitoring in pregnancy may be beneficial	16917026; 18626973; 18707767; 19261599; 19837590; 20012313; 20301347; 20458068; 20554332; 20562457; 20610155; 22661499; 22884442; 22911480; 23108489; 23219351; 23657916; 23790237; 23831158
DOLK	23406	22845	Congenital disorder of glycosylation, type Im	AR	Pediatric		Biochemical; Cardiovascular; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic	Cardiovascular; Hematologic	Hepatic-metabolized agents should be avoided	In  overall mildly affected individuals, cardiovascular manifestations such as dilated cardiomyopathy can result in severe sequelae, and early diagnosis may allow beneficial management;  Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	17273964; 22242004; 23890587
DPAGT1	2995	1798	Congenital myasthenic syndrome with tubular aggregates 2; Congenital disorder of glycosylation, type Ij (AR)	AR	Pediatric		Biochemical; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Genitourinary	Hematologic; Neurologic	Hepatic-metabolized agents should be avoided	Depending on the age of onset, individuals may present with findings such as hypotonia, gait problems, or falls, and medical treatment (eg, with anticholinesterases or agents that increase nerve terminal acetylcholine release) have been described as beneficial; In CDG, awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	12872255; 16870884; 22742743; 23249953; 23278575  
DPM1	3005	8813	Congenital disorder of glycosylation, type Ie	AR	Pediatric		Biochemical; Craniofacial; Neurologic; Ophthalmologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	642602; 10642597; 15669674; 16641202 
DPM2	3006	8818	Congenital disorder of glycosylation, type Iu	AR	Pediatric		Biochemical; Musculoskeletal; Neurologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	19901254; 23109149
DPM3	3007	54344	Congenital disorder of glycosylation, type Io	AR	Pediatric		Biochemical; Cardiovascular; Musculoskeletal; Neurologic	Cardiovascular; Hematologic	In a reported patient, dilated cardiomyopathy was the presenting complaint; Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	19576565
DPP6	3010	1804	Ventricular fibrillation, paroxysmal familial, 2	AD	Pediatric		Cardiovascular	Cardiovascular		Preventive measures and medical management may be helpful to help decrease morbidity; sudden cardiac death has been reported, including shortly following a normal cardiac examination	19285295
DPY19L2	19414	283417	Spermatogenic failure 9; Globozoospermia	AR	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15533374; 21397063; 21397064; 22627659; 22653751 
DPYD	3012	1806	5-fluorouracil toxicity	AD/AR	Pediatric	Allelic with Schizophrenia (AD)	General	Pharmacogenomic		Homozygous/compound heterozygous mutations can cause Dihydropyrimidine dehydrogenase deficiency; Severe toxicity can occur with certain medications (eg, 5-fluorouracil), and precautions may be beneficial	6488556; 2989687; 3335642; 8051923; 7832988; 9254861; 10027340; 10071185; 15303009; 19296131; 20544545; 20803296; 20920994; 21420945; 21553285; 21590448; 22410472; 22754590; 23042115
DPYS	3013	1807	Dihydropyriminidase deficiency	AR	Pediatric		Biochemical; Neurologic	Pharmacogenomic		Affected individuals could theoretically have severe toxicity with 5-fluorouracil; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1770794; 9323563; 9266350; 9718352; 17383919; 20362666 
DRD2	3023	1813	Myoclonic dystonia	AD	N/A	N/A	Musculoskeletal	General	Mutations have been implicated in Myoclonic dystonia, though the data are mixed	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10220438; 10716258; 12402271; 20301587 
DSC2	3036	1824	Arrhythmogenic right ventricular dysplasia, familial, 11; Arrhythmogenic right ventricular dysplasia with  palmoplantar keratoderma and woolly hair	AD/AR	Pediatric (Arrhythmogenic right ventricular dysplasia with  palmoplantar keratoderma and woolly hair); Adult (Arrhythmogenic right ventricular dysplasia, familial, 11)		Cardiovascular; Dermatologic	Cardiovascular		Individuals may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation 	12392835; 17033975; 17186466; 18957847; 20197793; 20301310
DSC3	3037	1825	Hypotrichosis and recurrent skin vesicles	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19765682
DSE	21144	29940	Ehlers-Danlos syndrome, musculocontractural type 2	AR	Pediatric		Cardiovascular; Craniofacial; Dental; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	Cardiovascular; Hematologic; Musculoskeletal		Extrapolating from similar types of Ehlers-Danlos syndrome, clinical issues relate to connective tissue fragility may affect multiple organs related to bleeding diatheses (eg, after minor trauma), such that recognition may allow precautions and preventive measures, as well as rapid treatment	23704329
DSG1	3048	1828	Severe dermatitis, multiple allergies, and metabolic wasting syndrome (SAM syndrome)	AR	Pediatric	Allelic with Keratosis palmoplantaris striata I (AD)	Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal; Neurologic	Allergy/Immunology/Infectious		Among manifestations affecting multiple organ systems, the condition may include susceptibility to frequent and severe infections, and prophylactic measures and early and aggressive treatment of infections may be beneficial	7544663; 10332028; 11313759; 16484817; 17194569; 19018793; 19157795; 19558595; 20082890; 23974871
DSG2	3049	1829	Cardiomyopathy, dilated, 1BB; Arrhythmogenic right ventricular dysplasia, familial, 10	AD	Pediatric		Cardiovascular	Cardiovascular		In Arrhythmogenic right ventricular dysplasia, familial, 10, individuals may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation; In Dilated cardiomyopathy; surveillance (eg, with echocardiography) may allow early detection of sequelae and medical management, which may decreased morbidity and mortality; Cardiac transplantation has been described	16773573; 16505173; 17105751; 18678517; 20301310 
DSG4	21307	147409	Hypotrichosis 6	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12705872; 16543896; 16439973; 16575393; 17392831; 21495994 
DSP	3052	1832	Arrhythmogenic right ventricular dysplasia, familial 8; Cardiomyopathy, dilated, with wooly hair and keratoderma	AD/AR	Pediatric	Allelic with Keratosis palmoplantaris striata II (AD); Epidermolysis bullosa, lethal acantholytic (AR)	Cardiovascular; Dermatologic	Cardiovascular	Homozygous/compound heterozygous mutations reported as causing biventricular dilative cardiomyopathy with palmoplantar keratoderma and woolly hair (Skin fragility-woolly hair syndrome)	Individuals may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation 	9738775; 9887343; 10902626; 11063735; 12373648; 11841538; 16175511; 21193976; 22527912; 22949226 
DSPP	3054	1834	Deafness, autosomal dominant, 39, with dentinogenesis imperfecta 1; Dentinogenesis imperfecta, Shields type II; Dentinogenesis imperfecta, Shields type III; Dentin dysplasia, type II  	AD	N/A	N/A	Audiologic/Otolaryngologic; Dental	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11175790; 11175779; 12354781; 15592686; 17686168; 18456718; 19026876; 19029076; 19103209; 19131317; 20121932; 20146806; 20618350; 20949630; 21029264; 21736673; 22125647; 22310900; 22521702 
DST	1090	667	Neuropathy, hereditary sensory and autonomic, type VI	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22522446
DSTYK	29043	25778	Congenital anomalies of the kidney and urinary tract	AD	Pediatric		Neurologic; Renal	Renal		Monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function	17273976; 23862974
DTNA	3057	1837	Left ventricular noncompaction 1	AD	Pediatric		Cardiovascular	Cardiovascular		The condition may affect cardiac function and may include arrhythmias, and surveillance (eg, with echocardiography and EKG), preventive measures, and medical management may be beneficial to  decrease morbidity	11238270; 16427346 
DTNBP1	17328	84062	Hermansky-Pudlak syndrome 7	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pharmacogenomic;  Pulmonary		Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination; Surveillance related to ophthalmologic, gastrointestinal, and other manifestations has been recommended in all individuals with HPS	12923531; 20301464
DUOX2	13273	50506	Thyroid dyshormonogenesis 6	AD/AR	Pediatric		Endocrine	Endocrine	Heterozygous mutations have been reported as typically resulting in transient congenital hypothyroidism, while bi-allelic mutations have been described as more frequently causing more severe and permanent forms of disease	Individuals may manifest with congenital or subclinical hypothyroidism, and medical treatment (with thyroid hormone replacement) may be effective	12110737; 16134168; 21565790; 23239635; 23457309
DUOXA2	32698	405753	Thyroid dyshormonogenesis 5	AR	Pediatric		Endocrine	Endocrine		Medical  treatment of hypothyroidism (eg, with T4) can be effective 	18042646; 21367925; 23292166
DUSP6	3072	1848	Hypogonadotropic hypogonadism 19, with or without anosmia	AD/Digenic	Pediatric		Audiologic/Otolaryngologic; Dental; Endocrine; Musculoskeletal; Neurologic	Endocrine	Relatively complex genetic models of disease have been described (eg, involving mutations in other FGF8-network-associated genes)	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	23643382
DUX4	50800	100288687	Facioscapulohumeral muscular dystrophy, type 2	Digenic (involving a SMCHD1 mutation and a permissive D4Z4 haplotype)	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23143600
DYM	21317	54808	Dyggve-Melchior-Clausen disease; Smith-McCort dysplasia	AR	N/A	N/A	Musculoskeletal	General	Atlanto-axial subluxation has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21032395; 1008064; 401564; 679519; 2213845; 1486701; 12491225; 12554689; 16470731; 19005420; 20865280; 22090722 
DYNC1H1	2961	1778	Charcot-Marie-Tooth disease, axonal, type 2O; Mental retardation, autosomal dominant 13; Spinal muscular atrophy, lower extremity, autosomal dominant 	AD	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20697106; 21076407; 21820100; 22459677; 22368300; 25140959
DYNC2H1	2962	79659	Short-rib thoracic dysplasia 3 with or without polydactyly	AR/Digenic 	N/A	N/A	Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	General	Digenic mutations in both NEK1 and DYNC2H1 can result in disease; The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19442771; 19361615; 21211617; 22499340; 22791528; 22499340
DYRK1A	3091	1859	Mental retardation, autosomal dominant 7	AD	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18405873; 21294719; 23099646; 23160955
DYRK1B	3092	9149	Abdominal obesity-metabolic syndrome 3	AD	Adult		Cardiovascular; Endocrine	Cardiovascular		Individuals have been reported as being affected by coronary artery disease, as well as stroke/sudden death, at a relatively young age, and preventive measures and surveillance may allow early management, potentially reducing morbidity and mortality	24827035
DYSF	3097	8291	Miyoshi muscular dystrophy 1; Muscular dystrophy, limb-girdle, type 2B; Myopathy, distal, with anterior tibial onset	AD/AR	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular		Individuals may have mild cardiac anomalies, as well as more severe cardiac manifestations such as dilated cardiomyopathy, and surveillance (eg, with echocardiogram)  may allow early detection and  management of sequelae	3942856;  9009996; 8808603; 9731527; 9731526; 10196377; 10469840;  11134403; 10766988; 11198284; 16087766; 17287450; 17994539; 18306167; 19084402; 20535123; 21522182; 22297152; 22517428; 21816046 
DYX1C1	21493	161582	Ciliary dyskinesia, primary 25	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	23872636
EARS2	29419	124454	Combined oxidative phosphorylation deficiency 12	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22492562; 23008233 
EBP	3133	10682	Chondrodysplasia punctata 2, X-linked dominant	XL	N/A	N/A	Biochemical; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	830452; 535904; 10391219; 10391218; 11038443; 12509714; 18573709; 21634086; 22121851; 22229330
ECE1	3146	1889	Hirschsprung disease, cardiac defects, and autonomic dysfunction	AD	N/A	N/A	Cardiovascular; Genitourinary; Musculoskeletal; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9915973
ECEL1	3147	9427	Arthrogryposis, distal, type 5D	AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23236030; 23261301; 25099528
ECM1	3153	1893	Lipoid proteinosis	AR	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Dermatologic; Neurologic; Pulmonary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5002423; 751090; 4087005; 11929856; 12603844; 19519837; 19734986; 21349189; 21791056; 21886756; 22182433 
EDA	3157	1896	Ectodermal dysplasia, anhidrotic, X-linked; Ectodermal dysplasia, hypohidrotic, X-linked;  Tooth agenesis, selective, X-linked, 1 (XL)	XL	N/A	N/A	Allergy/Immunology/Infectious; Craniofacial; Dental; Dermatologic	General	Frequent respiratory infections have been reported, possibly related to paucity/absence of mucus glands	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13913306; 5771499; 517571; 7446529; 2301459; 8434608; 8775234; 8696334; 9683615; 11388598; 17066260; 16583127; 17256800; 18657636; 18510547; 18231121; 18627052; 19533796; 22008666; 22350046 
EDAR	2895	10913	Ectodermal dysplasia, anhidrotic, autosomal recessive; Ectodermal dysplasia, anhidrotic, autosomal dominant; Hair morphology 1	AD/AR	N/A	N/A	Dental; Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Hair morphology 1 is of unclear clinical significance	10431241; 15373768; 16029325; 18816645; 18231121; 20979233; 21771270; 21876339; 22032522 
EDARADD	14341	128178	Ectodermal dysplasia, anhidrotic, autosomal recessive; Ectodermal dysplasia, anhidrotic, autosomal dominant; Ectodermal dysplasia, hypohidrotic, autosomal dominant; Ectodermal dysplasia, hypohidrotic, autosomal recessive	AD/AR	N/A	N/A	Dental; Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9245989; 11780064; 17354266; 20979233; 21626677; 21876339 
EDN1	3176	1906	Dominant Isolated Question-Mark Ears; Auriculocondylar Syndrome 3	AD/AR	N/A	N/A	Craniofacial	General	Conductive hearing loss has been described in one individual	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24268655
EDN3	3178	1908	Waardenburg syndrome, type 4B; Central hypoventilation syndrome, congenital	AD/AR	Pediatric		Audiologic/Otolaryngologic; Dermatologic; Gastrointestinal; Neurologic; Ophthalmologic; Pulmonary	Audiologic/Otolaryngologic; Gastrointestinal; Neurologic; Pulmonary		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Recognition of potential GI anomalies (eg, aganglionosis) may allow prompt treatment;  In Central hypoventilation syndrome, congenital, early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality	8696331; 8630502; 8630503; 9359047; 9279758; 10231870; 11303518; 19764030
EDNRB	3180	1910	Waardenburg syndrome type 4A; ABCD syndrome	AD/AR	Pediatric		Audiologic/Otolaryngologic; Dermatologic; Gastrointestinal; Ophthalmologic	Audiologic/Otolaryngologic; Gastrointestinal		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Recognition of potential GI manifestations (eg,  Hirschsprung disease) may allow prompt treatment	7264803; 8001158; 8634719; 7778600; 10528251; 11484199; 11891690; 19764031
EFEMP1	3218	2202	Doyne honeycomb degeneration of retina; Malattia leventinese 	AD/AR	N/A	N/A	Ophthalmologic	General	Photodynamic therapy may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10369267; 11384588; 11389162; 11825812; 12431256; 17666404; 22581936; 23036572 
EFEMP2	3219	30008	Cutis laxa, autosomal recessive type IB	AR	Pediatric		Cardiovascular; Dermatologic; Musculoskeletal; Pulmonary	Cardiovascular		Manifestations can include cardiovascular anomalies, including aortic dilatation and aortic aneurysms, and surveillance may allow early detection and management (eg, with beta-blockers and angiotensin-receptor inhibitors), which can decrease morbidity and mortality; Cigarette smoking should be avoided due to risk of exacerbation of pulmonary manifestations (including emphysema)	16685658; 17937443; 19664000; 20389311; 21563328; 22440127; 23212998
EFHC1	16406	114327	Epilepsy, myoclonic juvenile; Epilepsy, juvenile absence, susceptibility to, 1; Epilepsy, severe intractable	AD/AR	N/A	N/A	Neurologic	General	As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7668263; 12439895; 15258581; 17159113; 18505993; 19147686; 22690745; 22727576; 22926142 
EFNB1	3226	1947	Craniofrontonasal dysplasia	XL	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15166289; 15124102; 15959873; 16639408; 17941886; 18627045; 20734337; 21385071; 23509643
EFTUD2	30858	9343	Mandibulofacial dysostosis with microcephaly; Esophageal atresia, syndromic	AD	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic	Audiologic/Otolaryngologic	The condition may frequently be recognizable due to the presence of specific manifestations	Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Recognition of potential GI manifestations (eg,  Hirschsprung disease) may allow prompt treatment	16760738; 19334086; 22541558; 22305528; 23188108
EGF	3229	1950	Hypomagnesemia 4, renal	AR	Pediatric		Renal	Renal		Children may present with tetany and/or convulsions, and failure of early diagnosis (or treatment noncompliance) can be fatal or result in permanent neurological damage due to electrolyte abnormalities; Replacement therapy may be beneficial	3436090; 17671655
EGFR	3236	1956	Acute myeloid leukemia, familial; Lung cancer, familial, susceptibilty to; Inflammatory skin and bowel disease, neonatal, 2	AD/AR	Pediatric		Allergy/Immunology/Infectious; Cardiovascular; Oncologic	Allergy/Immunology/Infectious; Cardiovascular; Oncologic	In familial AML, one family has been reported, in which there was an inherited genomic ERBB rearrangement 	In Acute myeloid leukemia, familial and Lung cancer, familial, susceptibilty to, surveillance and early diagnosis related to the risk of malignancies (eg, including hematologic malaignancies and lung cancer)  could potentially be beneficial in order to allow early treatment; In  Inflammatory skin and bowel disease, neonatal, 2, antiinfectious prophylaxis and  early and aggressive treatment of infections may be beneficial, and individuals may also have cardiovascular manifestations such that surveillance may allow beneficial interventions	10686940; 16258541; 24691054
EGLN1	1232	54583	Erythrocytosis, familial, 3	AD	Pediatric	Allelic with Hemoglobin, high altitude adapation (AR)	Hematologic; Oncologic	Hematologic; Oncologic	In some described individuals, it has been suggested that manifestations involved increased risk of neoplasms as well as hematologic manifestations	Phlebotomy  can be used to maintain the hematocrit value in the desired range; Due to a reported increased risk of neoplasms, awareness may allow early detection and management, which may decrease associated morbidity and mortality	16407130; 17579185; 19092153; 20301715; 20466884; 20595611; 21275967; 21828119; 21904933; 25129147
EGR2	3239	1959	Charcot-Marie-Tooth disease, demyelinating, type 1D; Neuropathy, congenital hypomyelinating, 1 ; Dejerine-Sottas disease	AD/AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9537424; 10369870; 10371530; 11523566; 15947997; 21840889; 22271166; 22522483; 22546699; 22734907 
EHHADH	3247	1962	Fanconi renotubular syndrome 3	AD	Pediatric		Renal	Renal		Manifestations in the described individuals can include severe rickets, and early knowledge may allow medical/dietary interventions (eg, with calcitriol, and phosphate supplementation) to prevent (and treat) this complication	1627757; 24401050
EHMT1	24650	79813	Kleefstra syndrome	AD	N/A	N/A	Cardiovascular; Neurologic; Musculoskeletal	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16826528; 19264732; 21910222; 22670143; 23232695
EIF2AK3	3255	9451	Wolcott-Rallison syndrome	AR	Pediatric		Cardiovascular; Dental; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Renal	Endocrine		Individuals can have infantile-onset insulin-dependent diabetes mellitus (and may present with severe sequelae of diabetes, which may lead to death) prior to obvious manifestation of other, recognizable features, and prompt recognition and treatment could decrease morbidity and mortality, though treatment can be challenging	5008828; 7094931; 7551159; 9598721; 10932183; 12960215; 16813601; 21050479; 21648287; 21518408; 22672868; 23759358
EIF2AK4	19687	440275	Pulmonary venoocclusive disease 2	AR	Pediatric		Cardiovascular; Pulmonary	Cardiovascular; Pulmonary		Medical treatment (eg, with calcium antagonists, anticoagulants, prostanoids, endothelin receptor antagonists, etc.) may be beneficial, though lung transplantation may be required	24292273
EIF2B1	3257	1967	Leukoencephalopathy with vanishing white matter; Ovarioleukodystrophy	AR	Pediatric		Endocrine; Neurologic; Obstetric	Obstetric	The evidence is unclear, but it is possible that certain circumstances may aggravate the condition and accelerate neurological decline, including head trauma (children may benefit from wearing helmets), contact sports, and stressful situations (including high body temperature, and prophylactic measures and rapid treatment related to infections may be beneficial)	Individuals with Ovarioleukodystrophy may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desired	11704758; 11835386; 18263758; 20301435 
EIF2B2	3258	8892	Leukoencephalopathy with vanishing white matter; Ovarioleukodystrophy	AR	Pediatric		Endocrine; Neurologic; Obstetric	Obstetric	The evidence is unclear, but it is possible that certain circumstances may aggravate the condition and accelerate neurological decline, including head trauma (children may benefit from wearing helmets), contact sports, and stressful situations (including high body temperature, and prophylactic measures and rapid treatment related to infections may be beneficial)	Individuals with Ovarioleukodystrophy may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desired	11704758; 11835386; 14566705; 15054402; 18263758; 19625339; 21484434; 22285377; 20301435; 22678813; 22729508 
EIF2B3	3259	8891	Leukoencephalopathy with vanishing white matter; Ovarioleukodystrophy	AR	Pediatric		Endocrine; Neurologic; Obstetric	Obstetric	The evidence is unclear, but it is possible that certain circumstances may aggravate the condition and accelerate neurological decline, including head trauma (children may benefit from wearing helmets), contact sports, and stressful situations (including high body temperature, and prophylactic measures and rapid treatment related to infections may be beneficial)	Individuals with Ovarioleukodystrophy may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desired	11704758; 11835386; 15136673; 18263758; 19158808; 20301435; 21484434; 22312164; 23115207
EIF2B4	3260	8890	Leukoencephalopathy with vanishing white matter; Ovarioleukodystrophy	AR	Pediatric		Endocrine; Neurologic; Obstetric	Obstetric	The evidence is unclear, but it is possible that certain circumstances may aggravate the condition and accelerate neurological decline, including head trauma (children may benefit from wearing helmets), contact sports, and stressful situations (including high body temperature, and prophylactic measures and rapid treatment related to infections may be beneficial)	Individuals with Ovarioleukodystrophy may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desired	11704758; 11835386; 14566705; 15054402; 15776425; 18263758; 20301435 
EIF2B5	3261	8893	Leukoencephalopathy with vanishing white matter; Ovarioleukodystrophy	AR	Pediatric		Endocrine; Neurologic; Obstetric	Obstetric	The evidence is unclear, but it is possible that certain circumstances may aggravate the condition and accelerate neurological decline, including head trauma (children may benefit from wearing helmets), contact sports, and stressful situations (including high body temperature, and prophylactic measures and rapid treatment related to infections may be beneficial)	Individuals with Ovarioleukodystrophy may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desired	11704758; 12325082; 11835386; 14694060; 12707859; 14566705; 15054402; 15136673; 15136690; 15776425; 18263758; 19625339; 20301435; 20975056; 21676421; 22699478 
EIF4A3	18683	9775	Richieri-Costa-Pereira Syndrome	AR	N/A	N/A	Craniofacial; Musculoskeletal	General	The genetic cause involves a noncoding expansion	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24360810
EIF4G1	3296	1981	Parkinson disease 18	AD	N/A	N/A	Neurologic	General	Response to levodopa has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21907011; 23408866 
ELAC2	14198	60528	Combined oxidative phosphorylation deficiency 17	AR	Pediatric		Biochemical; Cardiovascular; Neurologic	Biochemical; Cardiovascular		The condition can include severe cardiac sequelae, such as hypertrophic cardiomyopathy, and though some individuals have been described as not responding to therapy, others have been reported as benefitting from  cardiac surveillance and early insitution of cardioprotective therapy and and biochemical dietary and medical treatment (eg, high-fat diet, coenzyme Q10, riboflavin, thiamine, and carnitine)	23849775
ELANE	3309	1991	Neutropenia, severe congenital 1, autosomal dominant; Neutropenia, cyclic	AD	Pediatric		Allergy/Immunology/Infectious; Oncologic	Allergy/Immunology/Infectious; Oncologic		Antiinfectious prophylaxis (including GCSF and related therapies) and early and aggressive treatment of infections may be beneficial; Surveillance and early treatment for malignancy may be beneficial; HSCT has been described for severe congenital neutropenia	13575153; 6050865; 4319697; 2471075; 2469956; 1282277; 8490166; 7529539; 8541539; 8989458; 8624368; 9116280; 9386665; 10581030; 11001877; 10887102; 17063141; 18028488; 17133096; 18611981; 19036076; 21072829; 22148006; 22080845; 22510773; 22624626; 22758217; 23454784; 23463630
ELMOD3	26158	84173	Deafness, autosomal recessive 88	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	24039609
ELN	3327	2006	Cutis laxa, autosomal dominant 1; Supravalvular aortic stenosis	AD	Pediatric		Cardiovascular; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Pulmonary	Cardiovascular	Individuals with Cutis Laxa may have a clinically recognizable phenotype,	In Cutis laxa, cardiovascular anomalies (eg, aortic aneuryms and pulmonary artery stenosis) are frequent, and surveillance to allow efficient detection and treatment/precautionary measures may be beneficial; In supravalvular aortic stenosis, there is a wide range of severity, including sudden infant death, and early diagnosis and treatment (eg, with surgery in some individuals) may reduce morbidity and mortality	5046633; 8475063; 8362925; 8364568; 8091333; 8132745; 8541862; 9215670; 9215671; 9873040; 11175284; 15955094; 16085695; 18348261; 19844261 
ELOVL4	14415	6785	Icthyosis, spastic quadriplegia, and mental retardation; Spinocerebellar ataxia 34; Startgardt disease 3	AD/AR	N/A	N/A	Biochemical; Dermatologic; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10634627; 11726641; 11138005; 15557430; 22100072; 24566826
ELOVL5	21308	60481	Spinocerebellar ataxia 39	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	25065913
EMD	3331	2010	Emery-Dreifuss muscular dystrophy 1, X-linked	XL	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular	Individuals, including females, can have serious cardiac conduction defects	Surveillance for and treatment of cardiac disease (eg, with EKG), including pacemaker implantation, may be beneficial	4567289; 3319295; 2685312; 7894480; 9195226; 10377322; 10323252; 10382910; 20301609; 21496632; 21697856 
EMG1	16912	10436	Bowen-Conradi syndrome	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	974244; 484596; 12838567; 15578624; 19463982
EMP2	3334	2013	Nephrotic syndrome, type 10	AR	N/A	N/A	Renal	General	Management with cyclophosphamide has been described as beneficial (frequent relapses have been described with steroid treatment)	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24814193
EMX2	3341	2018	Schizencephaly	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8528262; 9359037; 17506092; 18409201 
ENAM	3344	10117	Amelogenesis imperfecta, type IB; Amelogenesis imperfecta, type IC	AR	N/A	N/A	Dental 	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11487571; 11978766; 14684688; 22243262 
ENG	3349	2022	Hereditary hemorrhagic telangiectasia, type 1; Juvenile polyposis syndrome	AD	Pediatric		Cardiovascular; Gastrointestinal; Hematologic; Oncologic	Hematologic; Oncologic	Oncologic complications have been reported (in Juvenile polyposis syndrome), but the evidence appears overall unclear	Individuals may have a variety of vascular complications, such as arteriovenous malformations (eg, pulmonary arteriovenous malformations, which can lead to a number of complications, including cerebral abscesses) and bleeding diatheses, and surveillance and early intervention related to manifestations (eg, related to thromboembolism or hepatic disease) may decrease morbidity and mortality; Though the evidence is unclear, awareness of the possibly increased risk of neoplasms may allow early diagnosis and treatment, potentially decreasing morbidity and mortality	5656734; 4834927; 4050544; 3186989; 2658618; 2729347; 2036743; 1518020; 7894484; 7666879; 9354504; 9541302; 9753031; 10636073; 11006369; 12920067; 15024723; 16287957; 16470787; 16752392; 16155196; 16542389; 17204053; 18831062; 18312453; 19439755; 20301525; 23380110; 23440993; 23722869; 23919827; 23962120; 24001356
ENO3	3354	2027	Glycogen storage disease XIII	AR	N/A	N/A	Biochemical; Musculoskeletal	General	The reported individual had exercise intolerance and increased CK without myoglobinuria	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11506403
ENPP1	3356	5167	Hypophosphatemic rickets, autosomal recessive 2; Arterial calcification, generalized, of infancy, 1	AR	Pediatric	Allelic with Cole disease (AD)	Cardiovascular; Dermatologic; Musculoskeletal; Renal	Renal		For hypophosphatemic rickets, treatment (eg, with phosphates, vitamin D supplements) may be effective; In Arterial calcification, generalized, of infancy, 1, bisphosphonates have been described as beneficial in some	11159191; 12881724; 15940697; 19380683; 20016754; 19206175; 20137772; 20137773; 21745613; 21932012; 22629037; 22229486; 22209248; 24075184
ENTPD1	3363	953	Spastic paraplegia 64	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24482476
EOGT	28526	285203	Adams-Oliver syndrome 4	AR	N/A	N/A	Cardiovascular; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23522784
EP300	3373	2033	Rubinstein-Taybi syndrome 2	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General	The condition may include a risk of malignancy and frequent infections, as well as arrhythmia	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15706485; 17299436; 17220215; 19353645; 20014264; 20301699; 20717166; 21376300 
EPAS1	3374	2034	Erthyrocytosis, familial 4	AD	Pediatric		Hematologic; Oncologic	Hematologic; Oncologic	While presentation is typically described in adulthood, surveillance and treatment may be indicated in the pediatric time period	Individuals can present with manifestations secondary to erythrocytosis (eg, a DVT has been described in one individual), and interventions related to erythrocytosis (eg, venesection) have been described as beneficial; Due to a reported increased risk of neoplasms (eg, pheochromocytoma/paraganglioma), awareness may allow early detection and management, which may decrease associated morbidity and mortality	7747773; 18184961; 18456918; 18378852; 23090011
EPB41	3377	2035	Ellipsocytosis 1	AR	Pediatric		Hematologic	Hematologic		The recessive form is more severe, and due to anemia, individuals may require transfusions, and/or splenectomy	5731934; 7255153; 6894932; 7082842; 3965051; 3995181; 3755799; 3748797; 3674005; 1430200; 16730867; 14692233; 21839655 
EPB41L1	3378	2036	Mental retardation, autosomal dominant 11	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21376300
EPB42	3381	2038	Spherocytosis, type 5	AR	Pediatric		Hematologic	Hematologic		Due to anemia, individuals may require transfusions and/or splenectomy	4830746; 4413274; 2963832; 2386772; 2139792; 1558976; 7803799; 7772513; 9734643; 10406914; 12176912; 14636652; 19269200; 21275958 
EPCAM	11529	4072	Colorectal cancer, hereditary nonpolyposis, type 8; Diarrhea 5, with tufting enteropathy, congenital	AD/AR	Pediatric		Gastrointestinal; Musculoskeletal; Oncologic	Gastrointestinal; Oncologic	Specific deletions result in MSH2 inactivation; Although Colorectal cancer, hereditary nonpolyposis, type 8 typically manifests in adulthood, individuals have been reported such that familial screening would be recommended to commence during the pediatric period; Diarrhea 5, with tufting enteropathy, congenital may include additional features, such as dysmorphism	In HNPCC, for surveillance, colonoscopy with polyp removal is indicated starting at (whichever is earlier) age 20-25 years or 10 years prior to the earliest familial diagnosis; Prophylactic Hysterectomy with bilateral oophorectomy may be considered after childbearing is completed; For individuals with colon cancer, surgical treatment with full colectomy (and ileorectal anastomosis) is recommended; Cigarette smoking should be avoided; For other tumor types, awareness of cancer risk may allow early diagnosis and treatment, which may reduce morbidity and mortality; In Diarrhea 5, with tufting enteropathy, congenital, most affected individuals require parenteral nutrition for normal growth and development, and awareness can allow prompt medical/nutritional support	100367; 8057225; 16951683; 18572020; 19820410; 19098912; 20388775; 20301390; 21309036; 21227399 
EPG5	29331	57724	Vici syndrome	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Surveillance for cardiomyopathy (eg, including echocardiogram) may allow early management; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	20186778; 23222957
EPHA2	3386	1969	Cataract 6, multiple types	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19005574; 19649315; 20361013 
EPHX1	3401	2052	Hypercholanemia, familial	AR	Pediatric		Gastrointestinal	Gastrointestinal		As in other forms of familial hypercholanemia, individuals may respond to medical treatment (eg, with ursodeoxycholic acid)	12878321; 15768832 
EPM2A	3413	7957	Epilepsy, progressive myoclonic 2A (Lafora)	AR	N/A	N/A	Neurologic	General	Some antiepileptic drugs may be effective, but certain medications (eg, phenytoin, and possibly carbamazepine, oxcarbazepine, and lamotrigine) can exacerbate myoclonus	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9771710; 10513696; 14663053; 15277643; 16157917; 16356781; 20301563 
EPOR	3416	2057	Erythrocytosis, familial, 1	AD	Pediatric		Hematologic	Hematologic		Phlebotomy  can be used to maintain the hematocrit value in the desired range	4052634; 1954391; 093406; 9292543; 9649565; 20700488; 21437635 
EPS8	3420	2059	Deafness, autosomal recessive 102	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	24741995
EPX	3423	8288	Eosinophil peroxidase deficiency	AR	N/A	N/A	General	General		The clinical relevance is unclear	7809065
ERBB3	3431	2065	Lethal congenital contractural syndrome 2	AR	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Renal	General	Individuals can have manifestations including cardiovascular anomalies (eg,cardiomyopathy and ventricular septal defects have been described) and hydronephrosis without urinary bladder abnormality	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12548738; 17701904
ERBB4	3432	2066	Amyotrophic lateral sclerosis 19	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24119685
ERCC1	3433	2067	Cerebrooculofacioskeletal syndrome 4	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17273966; 23623389
ERCC2	3434	2068	Trichothiodystrophy; Xeroderma pigmentosum, group D	AR	Pediatric	Allelic with Cerebrooculofacioskeletal syndrome  (AR)	Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic	Allergy/Immunology/Infectious; Dermatologic; Oncologic		In Trichothiodystrophy, individuals may be at high risk for skin cancer, and preventive measures may be beneficial; Frequent infections have been reported, and prophylaxis and early and aggressive treatment of infections may be beneficial; In XP, skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance can be beneficial	2189905; 1372108; 7802014; 8783572; 11709541; 11443545; 21959366; 20301571
ERCC3	3435	2071	Xeroderma pigmentosum, complementation group B; Trichothiodystrophy	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic	Allergy/Immunology/Infectious; Dermatologic; Oncologic		In Trichothiodystrophy, individuals may be at high risk for skin cancer, and preventive measures may be beneficial; Frequent infections have been reported, and prophylaxis and early and aggressive treatment of infections may be beneficial; In XP, skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance (primarily related to skin manifestations, as well as other sequelae) can be beneficial	4811796; 6185841; 2189905; 2167179; 8783572; 9012405; 16947863; 20301571
ERCC4	3436	2072	Fanconi anemia, complementation group Q; Xeroderma pigmentosum, group F	AR	Pediatric	Allelic with XFE progeroid syndrome (AR)	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Dermatologic; Hematologic; Oncologic	Fanconi anemia can involve multiple congenital anomalies	In XP, skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance (primarily related to skin manifestations, as well as other sequelae) can be beneficial; In Fanconi anemia, specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended	3834095; 3372781; 2696553; 8427828; 10447254; 17183314; 20301571; 23623386
ERCC5	3437	2073	Xeroderma pigmentosum, group G; Xeroderma pigmentosum, group G/Cockayne syndrome	AR	Pediatric	Allelic with Cerebrooculofacioskeletal syndrome 3 (AR)	Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic	Dermatologic; Oncologic		Skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance for dermatologic manifestations can be beneficial	492197; 11219864; 3620347; 8317483; 8818951; 9096355; 11228268; 11841555; 20301571
ERCC6	3438	2074	Xeroderma Pigmentosum-Cockayne Syndrome; De Sanctis-Cacchione syndrome	AD/AR	Pediatric	Allelic with Cerebrooculofacioskeletal syndrome (AR); UV-sensitive syndrome (AR), in which individuals have sun senstivity, but are not reported to have skin cancer	Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic	Dermatologic; Oncologic	Individuals with Cockayne syndrome without skin sensitivity have been described	Some individuals with Xeroderma Pigmentosum-Cockayne Syndrome  can have predisposition to skin cancer; Skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance for dermatologic manifestations can be beneficial	14246158; 5560051; 4211825; 4431498; 7264357; 3545087; 1372469; 9443879; 9777763; 10196384; 10767341; 10739753; 15486090; 18446857; 18628313;  20456449; 20301571; 22466610
ERCC6L2	26922	375748	Bone marrow failure syndrome 2	AR	Pediatric		Hematologic; Neurologic	Hematologic		Individuals have been described with tri-lineage bone marrow failure, and awareness may allow prompt recognition and management related to hematologic  (eg, anemia) and infectious sequelae	24507776
ERCC8	3439	1161	UV-sensitive syndrome 2; Cockayne syndrome type A	AR	N/A	N/A	Dermatologic; Musculoskeletal; Neurologic	General	In Cockayne syndrome, some neurological manifestations have been reported as responding to treatment with carbidopa-levodopa; UV-sensitive syndrome 2 has not been described as associated with increased risk of skin cancer	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14783428; 1308368; 7664335; 9443879; 11185579; 14661080; 15744458; 16865293; 18695064;  19329487; 19894250; 21108394
ERLIN2	1356	11160	Spastic paraplegia 18, autosomal recessive	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21330303; 23109145
ERMAP	15743	114625	Blood group, Scianna system; Blood group, Radin	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	7998072; 12393480; 15954808
ERMARD	21056	55780	Periventricular nodular heterotopia 6	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24056535
ESAM	17474	90952	Schizophrenia	AD	N/A	N/A	Neurologic	General		Evidence or clinical applicability is unclear	21822266
ESCO2	27230	157570	SC phocomelia syndrome; Roberts syndrome	AR	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	General	Individuals have been described developing complications such as cardiovascular complications	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7067161; 3740099; 1642282; 16380922; 15821733; 18411254; 19574259
ESPN	13281	83715	Deafness, autosomal dominant, without vestibular involvement; Deafness, autosomal recessive 36	AD/AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	15286153; 15930085; 18973245 
ESR1	3467	2099	Estrogen resistance	AR	N/A	N/A	Endocrine	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8090165; 8961262; 9396482; 18505767; 23841731
ESRRB	3473	2103	Deafness, autosomal recessive 35	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	12529709; 18179891
ETFA	3481	2108	Multiple acyl-CoA dehydrogenase deficiency; Glutaric aciduria II	AR	Pediatric		Biochemical; Gastrointestinal; Musculoskeletal; Neurologic; Renal	Biochemical		Dietary measures (fasting avoidance and low-fat diet, as well as supplementation, such as with riboflavin and carnitine) may be beneficial	7145508; 8771170; 1882842; 1430199; 12815589; 18289905; 20736750; 22231380
ETFB	3482	2109	Multiple acyl-CoA dehydrogenase deficiency; Glutaric aciduria II	AR	Pediatric		Biochemical; Gastrointestinal; Musculoskeletal; Neurologic; Renal	Biochemical		Dietary measures (fasting avoidance and low-fat diet, as well as supplementation, such as with riboflavin and carnitine) may be beneficial	7145508; 8771170; 7912128; 12706375; 12815589; 18289905; 22231380
ETFDH	3483	2110	Multiple acyl-CoA dehydrogenase deficiency; Glutaric aciduria II	AR	Pediatric		Biochemical; Gastrointestinal; Musculoskeletal; Neurologic; Renal	Biochemical		Dietary measures (fasting avoidance and low-fat diet, as well as supplementation, such as with riboflavin and carnitine) may be beneficial	7145508; 8771170; 12815589; 16527485; 17412732; 17584774; 18289905; 19208393; 19249206; 19758981; 19783111; 20138856; 20370797; 20837308; 21088898; 21616504; 21907580; 22041377; 22231380; 22664151; 23106979; 23893693
ETHE1	23287	23474	Ethylmalonic encephalopathy	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Neurologic	Biochemical		The condition can manifest with features including neurological impairment and chronic diarrhea, and dietary (eg, with restriction of branched amino acids, fatty acids, and methionine) and medical treatment (eg, with metronidazole and N-acetylcysteine) has been reported as having clinical benefit	14732903; 18593870; 20528888; 20657580; 20978941; 21472225; 22584649; 22805253
EVC	3497	2121	Ellis-van Creveld syndrome; Weyers acrofacial dysostosis	AD/AR	N/A	N/A	Cardiovascular; Craniofacial; Dental; Dermatologic; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7628126; 10700184; 17024374; 18454448; 18947413; 19744229; 20184732; 23220543
EVC2	19747	132884	Ellis-van Creveld syndrome; Weyers acrodental dysostosis	AD/AR	N/A	N/A	Cardiovascular; Craniofacial; Dental; Dermatologic; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12468274; 12571802; 16404586; 17024374; 20184732; 21815252; 22406498; 23026208; 23220543; 23276573
EXOSC3	17944	51010	Pontocerebellar hypoplasia type 1B	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11020648;  12731647; 22544365; 24524299
EXOSC8	17035	11340	Pontocerebellar hypoplasia, type 1C	AR	N/A	N/A	Audiologic/Otolaryngologic; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24989451
EXPH5	30578	23086	Epidermolysis bullosa, nonspecific, autosomal recessive	AR	N/A	N/A	Dermatologic	General	Though appropriate skin care may be beneficial, it is unclear if early (genetic) diagnosis would be additionally advantageous	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23176819
EXT1	3512	2131	Exostoses, multiple, type 1	AD	Pediatric		Musculoskeletal; Oncologic	Oncologic	Though onset of malignancy is typically described in adulthood, some individuals have been affected at an earlier age; Germline mutations have also been implicated in chondrosarcoma	Though data regarding the efficacy of surveillance are lacking, individuals are at risk for the (relatively infrequent) development of malignant change of exostoses, and awareness may allow early detection and management	7550340; 8981950; 9326317; 9521425; 9463333; 10679937; 11432960; 11170095; 15253765; 16879194; 19344451; 20301413; 22258776; 23629877; 23770606
EXT2	3513	2132	Exostoses, multiple, type 2	AD	Pediatric		Musculoskeletal; Oncologic	Oncologic	Though onset of malignancy is typically described in adulthood, some individuals have been affected at an earlier age; Germline mutations have also been implicated in chondrosarcoma	Though data regarding the efficacy of surveillance are lacking, individuals are at risk for the (relatively infrequent) development of malignant change of exostoses, and awareness may allow early detection and management	7726168; 8782816; 8894688; 9326317; 9463333; 10679937; 11432960; 16879194; 19344451; 20301413; 22258776; 23629877; 23770606
EYA1	3519	2138	Branchiootic syndrome 1; Branchiootorenal syndrome 1; Otofaciocervical syndrome	AD	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Ophthalmologic; Renal	Audiologic/Otolaryngologic; Renal	Individuals can have characteristic aural anomalies, but these may not be readily ascertained; In BOR, surveillance and treatment/prophylaxis related to renal manifestations can be beneficial	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In BOR, surveillance and treatment/prophylaxis related to vesicoureteral reflux can be beneficial	9020840; 9359046; 10991693; 11409867; 12404110; 15146463; 16441263; 16691597; 18177466; 18220287; 20301554; 19206155
EYA4	3522	2070	Cardiomyopathy, dilated, 1J	AD	Adult	Allelic with Deafness, autosomal dominant 10 (AD)	Audiologic/Otolaryngologic; Cardiovascular	Cardiovascular	The condition may also include childhood-onset sensorineural hearing loss	Related to cardiomyopathy, preventive measures and medical management may be helpful to help decrease morbidity	10769282; 10982027; 11159937; 15735644; 17568404; 17567890 
EYS	21555	346007	Retitinis pigmentosa 25	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18836446; 18976725; 21069908; 21179430; 21519034; 22277662; 22302105; 22363543 
EZH2	3527	2146	Weaver syndrome 2	AD	N/A	N/A	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4366187; 22177091
F10	3528	2159	Factor X deficiency	AR	Pediatric		Hematologic	Hematologic; Pharmacogenomic		Individuals can suffer from bleeding diatheses of varying severity, and preventive measures related to bleeding episodes can be beneficial, including in special circumstances such as pregnancy; Precautions should be taken related to certain agents that may provoke/worsen bleeding risk	5450692; 4989292; 4995085; 3732313; 8192155; 3408671; 2567188; 2790181; 1985698; 1997381; 9695984; 10746568; 12028042; 22151249; 22460599; 22506295 
F11	3529	2160	Factor XI deficiency	AD/AR	Pediatric		Hematologic	Hematologic; Pharmacogenomic	Heterozygotes may have manifestations that warrant interventions	Individuals may be at risk of bleeding (eg, following surgery or with injury, and during delivery), and prophylaxis and preventive measures (eg, including avoidance of aspirin) and prompt treatment (eg, with fresh frozen plasma) may be beneficial, including considerations prior to/during pregnancy; Antifibrinolytic therapy may be beneficial in females with menorrhagia	3871646; 2439152; 3553944; 2813350; 8800510; 18434707; 18160615; 19598070; 19367158; 19049995; 21577094; 21699628; 22624777; 22726099
F12	3530	2161	Angioedema, hereditary, type III	AD/AR	Pediatric	Allelic with Factor XII deficiency (AD) (in which, though the evidence is mixed, individuals do not appear to have a predisposition to severe bleeding diatheses or thromboembolic complications)	Allergy/Immunology/Infectious; Hematologic	Allergy/Immunology/Infectious; Pharmacogenomic		Attacks, which can include potentially life-threatening upper airway obstruction, can be precipitated by high estrogen levels (eg, pregnancy, OCPs)	14490552; 4968868; 5432188; 6348471; 2882793; 2110579; 1905067; 8419231; 7947293; 11069485; 15306750; 15013868; 15678272; 19477491; 20729721; 20667118; 20695852; 21849258; 20729721; 21297451; 22043782; 22801442; 22197449; 22729959 
F13A1	3531	2162	Factor XIIIA deficiency	AR	Pediatric		Hematologic	Hematologic; Pharmacogenomic		Individuals have increased bleeding and poor wound healing; awareness and management of bleeding risk in certain situations (eg, obstetric event or surgery) may decrease morbidity; Precautions should be taken related to certain agents that may provoke/worsen bleeding risk	1644910; 8025280; 7727776; 8547636; 9459313; 10365735; 12072871; 12456499; 17393027; 19438481; 20108427; 21512576 
F13B	3534	2165	Factor XIIIB deficiency	AR	Pediatric		Hematologic	Hematologic; Pharmacogenomic		Individuals have increased bleeding and poor wound healing; awareness and management of bleeding risk in certain situations (eg, obstetric event or surgery) may decrease morbidity; Precautions should be taken related to certain agents that may provoke/worsen bleeding risk	2334637; 8324218; 11313256; 20331752; 21640452 
F2	3535	2147	Prothrombin deficiency, congenital; Thrombophilia due to thrombin defect 	AD/AR	Pediatric		Hematologic	Hematologic; Pharmacogenomic	Variants in F2 may interact with variants in other genes, such as F5, to result in susceptibility to hematologic manifestations; Heterozygous mutations associated with Prothrombin deficiency  have been described as demonstrating increased bleeding tendency, such as post-dental or surgical bleeding	In individuals with Thrombophilia due to thrombin defect , as relates to the specific 20210G-A variant, mutation carriers may benefit from preventive measures and/or other interventions when other risk factors are present or in symptomatic disease; In AR forms of disease (Prothrombin deficiency), surveillance and prompt treatment of bleeding diatheses may reduce morbidity; Precautions should be taken related to certain agents that may provoke/worsen bleeding risk	4489469; 7740448; 8916933; 9869612; 10233438; 10477778; 11734673; 10666427; 11167765; 11506076; 15534175; 19598065; 22716977 
F5	3542	2153	Thrombophilia due to activated protein C resistance; Factor V deficiency	AD/AR	Pediatric	FVL (R506Q, 612309.0001) has also been reported as associated with multiple susceptibilities and other conditions	Hematologic	Hematologic; Pharmacogenomic	Variants in F5 may interact with variants in other genes, such as F2 and MTHFR, to result in susceptibility to hematologic manifestations	In Thrombophilia due to activated protein C resistance, surveillance and treatment (including preventive measures in some individuals) may reduce morbidity; Precautions should be taken regarding the avoidance of certain medications (eg, estrogen-containing OCPs); Individuals with Factor V deficiency can suffer from bleeding diatheses of varying severity, and preventive measures, as well as prompt treatment (eg, with fresh frozen plasma or platelet transfusion in instances of severe bleeding) related to bleeding episodes can be beneficial	20293060; 13194849; 13575936; 1239529; 694421; 6348091; 6479988; 8430067; 7803250; 8108421; 8164741; 7910348; 7969326; 8049422; 7911872; 7911873; 7989612; 7586244; 7877648; 8616100; 8627449; 8639453; 8815565; 9207293; 9245936; 9010145; 9372726; 9518910; 9577282; 9877047; 9576178; 9846775; 9734642; 9459326; 9462312; 9488630; 9454742; 10233438; 10477778; 10066036; 10328130; 9878639; 10507841; 10666427; 11001884; 11018168; 11167765; 10943572; 11532625; 11435304; 11781258; 11859850; 12138364; 12393490; 12393635; 14617013; 15534175; 15293282; 14673478; 14996674; 16113779; 16551553; 16707754; 16606808; 19531787; 21292261; 21320286; 21730834; 21777354; 22251029; 22758216; 22888854; 22990475; 23034579 
F7	3544	2155	Factor VII deficiency	AR	Pediatric		Hematologic	Hematologic; Pharmacogenomic		Individuals can suffer from bleeding diatheses of varying severity, and preventive measures and prompt treatment (including with factor replacement therapy) related to bleeding episodes can be beneficial; Precautions should be taken related to certain agents that may provoke/worsen bleeding risk	7919338; 7981691; 8652821; 8883260; 9680360; 11091194; 10984565; 11129332; 10862079; 11225604; 11139238; 11260055; 12181036; 11529858; 22188821; 22327818; 22356641; 22628013; 22684392; 22845882; 22873696; 22974900 
F8	3546	2157	Hemophilia A	XL	Pediatric		Hematologic	Hematologic; Pharmacogenomic		Plasma-derived factor VIII concentrate and/or desmopressin can be used to treat/prevent bleeding; Other considerations may be beneficial in specific circumstances, such as in postpartum females; Certain circumstances should be avoided or need to be specifically managed, such as circumcision, high-risk activities, and medications such as aspirin	13739554; 2987704; 3012775; 3035554; 3097553; 3338800; 3131627; 2833855; 2835904; 3139545; 1688823; 2123300; 1357455; 8275087; 8281136; 8259143; 7662970; 3893256; 8644728; 8968748; 9042915; 11023529; 11396445; 11857744; 12907007; 16786531; 16551972; 18691168; 18217193; 20301578; 21056901; 22507546; 22621702; 22639879; 22866674; 23005041; 23025325; 23047359; 23067060 
F9	3551	2158	Hemophilia B; Thrombophilia, X-linked, due to factor IX defect; Warfarin sensitivity	XL	Pediatric		Hematologic	Hematologic; Pharmacogenomic		In Hemophilia B, recombinant or plasma-derived factor IX concentrate can be effective for prevention/treatment of bleeding episodes; Other considerations may be beneficial in specific circumstances, such as in postpartum females; Certain circumstances should be avoided or need to be specifically managed, such as circumcision, high-risk activities, and medications such as aspirin; In X-linked thrombophilia, preventive measures related to thrombophilia, as well as early  recognition and treatment of manifestations such as deep venous thromboses, may reduce morbidity	14920537; 12997790; 4163943; 4972271; 5781711; 5450691; 734633; 7062952; 6142993; 3001143; 2907054; 3219291; 2841226; 2570235; 1768766; 1873221; 1601420; 8392713; 8352232; 8096443; 8304338; 8594556; 8833911; 9016521; 9233593; 10845896;  11122385; 11328285; 18349091; 18624978; 19251637; 19815722; 19846852; 20301668; 21056901 
FA2H	21197	79152	Spastic paraplegia 35, autosomal recessive	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18463364; 19068277; 20104589; 20853438; 22146942; 22925154; 23745665
FADD	3573	8772	Infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovascular malformations	AR	Pediatric		Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Neurologic	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Patients suffer from stereotypical episodes of fever, liver dyfunction, and encephalopathy, which may be severe and precipitated by viral infections; Other findings, such as cardiovascular malformations, and fucntional hyposplenism, have been described	21109225
FAH	3579	2184	Tyrosinemia, type I	AR	Pediatric		Biochemical; Gastrointestinal; Musculoskeletal; Oncologic; Renal	Biochemical; Oncologic		Dietary (controlled intake of phenylalanine and tyrosine) and medical (eg, nitsinone) treatment can be beneficial, and may reduce risks related to manifestations (eg, hepatocellular carcinoma) that are part of the natural history in untreated individuals; Some individuals require liver transplantation	14085846; 14271358; 6016174; 2536631; 2153931; 2378357; 1383656; 1440864; 8028615; 7977370; 7603784; 8829657; 9101289; 9728331; 10603099; 11575602; 12203990; 15759101; 20301688; 22554029 
FAM111B	24200	374393	Hereditary Fibrosing Poikiloderma with Tendon Contracture, Myopathy, and Pulmonary Fibrosis	AD	N/A	N/A	Dermatologic; Musculoskeletal; Pulmonary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24268661
FAM126A	24587	84668	Leukodystrophy, hypomyelinating, 5	AR	N/A	N/A	Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16951682
FAM134B	25964	54463	Neuropathy, hereditary sensory and autonomic, type IIB	AR	N/A	N/A	Neurologic	General	Insensitivity to pain can result in injuries and infections	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19838196
FAM161A	25808	84140	Retitinis pigmentosa 28	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10507729; 20705279; 20705278  
FAM20A	23015	54757	Amelogenesis imperfecta, type IG (Enamel-renal syndrome)	AR	N/A	N/A	Dental	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18597613; 21549343; 21990045; 23434854; 24196488
FAM20C	22140	56975	Hypophosphatemia,hyperphosphaturia, dental anomalies, intracerebral calcifications and osteosclerosis (Raine syndrome)	AR	Pediatric		Craniofacial; Dental; Musculoskeletal; Neurologic; Renal	Renal		The condition includes hypophosphatemia an urinary phosphate wasting, and medical management  (with oral phosphate supplements) has been described, and may be beneficial	2614802; 2020859; 12868469; 14564151; 17924334; 19250384; 20825432; 23325605 
FAM58A	28434	92002	STAR syndrome; Toe syndactyly, telecanthus, and anogenital and renal malformations	XL	N/A	N/A	Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Renal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8818947; 18297069
FAM83H	24797	286077	Amelogenesis imperfecta, type 3	AD	N/A	N/A	Dental	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18252228; 18484629; 19220331; 19407157; 21702852; 23355523 
FAN1	29170	22909	Interstitial nephritis, karyomegalic	AR	N/A	N/A	Gastrointestinal; Renal	General	Individuals may suffer renal failure, and renal transplant has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7847351; 8546134; 16678356; 17304531; 22772369
FANCA	3582	2175	Fanconi anemia, complementation group A	AR	Pediatric		Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Hematologic; Oncologic	Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended	13826667; 6338978; 2571931; 1536187; 1521091; 8502512; 8081006; 8781414; 9371798; 10094191; 11389461; 14504102; 14605744; 17105750; 20301575; 20507306; 21273304; 22480464; 22950077; 23067021; 23898106; 23973728
FANCB	3583	2187	Fanconi anemia,complementation group B	XL	Pediatric		Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Hematologic; Oncologic	Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended	15502827; 16679491; 20301575; 21910217; 22052692 
FANCC	3584	2176	Fanconi anemia, complementation group C	AR	Pediatric		Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Hematologic; Oncologic	Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended	1574115; 9272737; 10431244; 20301575; 22160080; 22701786; 23028338 
FANCD2	3585	2177	Fanconi anemia, complementation group D2	AR	Pediatric		Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Hematologic; Oncologic	Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended	17436244; 20301575; 22720145; 23285130  
FANCE	3586	2178	Fanconi anemia, complementation group E	AR	Pediatric		Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Hematologic; Oncologic	Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended	11001585; 17924555; 20301575; 22778927 
FANCF	3587	2188	Fanconia anemia, complementation group F	AR	Pediatric		Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Hematologic; Oncologic	Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended	10615118; 20301575
FANCG	3588	2189	Fanconi anemia type G	AR	Pediatric		Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Hematologic; Oncologic	Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended	9806548; 20301575
FANCI	25568	55215	Fanconi anemia, complementation group I	AR	Pediatric		Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Hematologic; Oncologic	Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended	14630800; 17452773; 17460694; 17412408; 20301575; 21568838
FANCL	20748	55120	Fanconi anemia type L	AR	Pediatric		Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Hematologic; Oncologic	Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended	12973351; 20301575; 22720145 
FANCM	23168	57697	Fanconi anemia type M	AR	Pediatric		Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Hematologic; Oncologic	Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended	16116422; 20301575
FARS2	21062	10667	Combined oxidative phosphorylation deficiency 14	AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22499341; 22833457
FAS	11920	355	Autoimmune lymphoproliferative syndrome, type IA	AD/AR	Pediatric		Allergy/Immunology/Infectious; Hematologic; Oncologic; Renal	Allergy/Immunology/Infectious; Oncologic		Lymphoproliferation can be suppressed with medications such as corticosteroids, cyclosporine, tacrolimus, sirolimus, and mycophenolate mofetil; BMT/HSCT the only curative treatment for ALPS, has to date mostly been reported in patients with severe clinical findings; Surveillance for manifestations of lymphoproliferation and autoimmunity, and specialized imaging studies to detect malignant transformation may be beneficial 	4165068; 1386609; 7540117; 8929361; 10709732; 15459302; 20301287 
FASLG	11936	356	Autoimmune lymphoproliferative syndrome, type IB	AD	Pediatric		Allergy/Immunology/Infectious; Hematologic; Oncologic; Renal	Allergy/Immunology/Infectious; Oncologic	Biallelic mutations have been described as resulting in more severe presentations, including as relates to autoimmunity and lymphoproliferation	Lymphoproliferation can be suppressed with medications such as corticosteroids, cyclosporine, tacrolimus, sirolimus, and mycophenolate mofetil; BMT/HSCT the only curative treatment for ALPS, has to date mostly been reported in patients with severe clinical findings; Surveillance for manifestations of lymphoproliferation and autoimmunity, and specialized imaging studies to detect malignant transformation may be beneficial	8787672; 15004557; 16627752; 17605793; 20301287
FASTKD2	29160	22868	Mitochondrial complex IV deficiency	AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18771761
FAT4	23109	79633	Hennekam lymphangiectasia-lymphedema syndrome 2	AR	Pediatric	Allelic with Van Maldergem syndrome 2 (AR)	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Dental; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	Allergy/Immunology/Infectious; Gastrointestinal		The condition can include manifestations such as protein-losing enteropathy (which may be refractory), as well as features for which treatment can be beneficial, such as infectious sequelae, for which early and aggressive treatment may be beneficial	2624276; 22469822; 22473091; 24056717; 24913602
FBLN1	3600	2192	Synpolydactyly 2	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; In Cutis laxa, individuals can have cardiac manifestations such as supravalvular aortic stenosis, but the condition should be recognizable	8831136; 11836357
FBLN5	3602	10516	Macular degeneration, age-related 3 (AD); Cutis laxa, autosomal dominant 2; Cutis laxa, autosomal recessive, type IA	AD/AR	N/A	N/A	Dermatologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12189163; 12618961; 15269314; 20301756; 22829427
FBN1	3603	2200	Marfan syndrome; MASS syndrome; Shprintzen-Goldberg syndrome	AD	Pediatric	Allelic with Geleophysic dysplasia 2 (AD); Weill-Marchesani syndrome 2 (AD); Acromicric dysplasia (AD); Stiff skin syndrome (AD); Ectopia lentis, familial (AD)	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary	Cardiovascular; Musculoskeletal; Ophthalmologic; Pharmacogenomic; Pulmonary		Medications that reduce aortic wall hemodynamic stress (eg, beta blockers) have been shown to be effective; Afterload-reducing agents can improve cardiovascular function in CHF; Surgical aortic repair is indicated depending on parameters such as size and rate of change of aorta; Other issues also require attention and may benefit from regular surveillance, such as those involving ophthalomologic, pulmonary, and skeletal complications; Certain agents and circumstances should be avoided, including activities that impose cardiovascular or musculoskeletal risk, as well as agents such as decongestants, caffeine; LASIK is typically contraindicated	1157278; 370588; 6182156; 2938007; 3189335; 2322060; 1852208; 2337033; 1864149; 1301946; 1569206; 1736263; 1542340; 8406497; 7802039; 7573130; 8152445; 8863159; 8733052; 8790089; 8563763; 9150726; 9761390; 10489951; 10219065; 11256662; 11700157; 12446365; 11845856; 11826022; 12525539; 14598350; 15054843; 15731757; 15517394; 16596670; 16202954; 17366579; 18579813; 19996017; 19353630; 20375004; 20301510; 20301776; 20886638; 21063442; 21683322; 21883168; 21932315; 22034023; 22461464; 22736615; 22876116; 22950452 
FBN2	3604	2201	Congenital contractural arachnodactyly (Beals syndrome)	AD	Pediatric	Allelic with Macular degeneration, early onset (AD)	Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Ophthalmologic	Cardiovascular		The condition may be clinically recognizable in most individuals, but individuals may have cardiovascular manifestations including aortic root dilatation, and surveillance and early interventions may reduce morbidity and mortality	7493032; 7633409; 8900230; 9106527; 9714438; 10797416; 11754102; 16531736; 20301560; 24899048
FBP1	3606	2203	Fructose-1,6-bisphosphatase deficiency	AR	Pediatric		Biochemical	Biochemical		The condition may be lethal in the perinatal period, but prompt recognition and treatment of lactic acidosis and hypoglycemia (eg, with IV/oral glucose, sodium bicarbonate) can be effective	4193749; 4335192; 4341454; 4341015; 175754; 2347355; 1995492; 9382095; 12126934; 17705024; 19259699; 20096900; 22158280 
FBXL4	13601	26235	Mitochondrial DNA depletion syndrome 13	AR	N/A	N/A	Biochemical; Craniofacial; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23993193; 23993194
FBXO31	16510	79791	Mental retardation 45, autosomal recessive	AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24623383
FBXO38	28844	81545	Neuronopathy, distal hereditary motor, type IID	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7723953; 24207122
FBXO7	13586	25793	Parkinson disease 15, autosomal recessive	AR	N/A	N/A	Neurologic	General	Individuals have been described with levodopa response 	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18513678; 19038853; 23318512
FCGR3A	3619	2214	Immunodeficiency 20	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals have been described as affected by early-onset severe herpes viral infections (eg, EBV, HPV), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	8608639; 8874200; 23006327
FCN3	3625	8547	Immunodeficiency due to Ficolin 3 deficiency	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Sequelae have been described as including frequent and severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	19535802
FECH	3647	2235	Protoporphyria, erythropoietic	AD/AR	Pediatric		Dermatologic; Gastrointestinal; Hematologic 	Dermatologic; Gastrointestinal	The inheritance pattern can be complex, and can involve a deleterious mutation in trans with a "low-normal" polymorphism (sometimes termed "pseudodominant" inheritance), as well as homozygosity/compound heterozygosity for deleterious mutations; Agents associated with hepatic dysfunction should be avoided	While the only manifestation in many individuals is photosensitivity (for which light avoidance and possible medical treatment, such as with alpha-melanocyte-stimulating hormone analog, can be beneficial), some individuals can have severe liver sequelae, and surveillance and medical treatment (eg, with cholestyramine) can be beneficial; BMT and liver transplantation may be necessary	14072370; 5835322; 14338805; 6019665; 5536249; 1138541; 1251847; 911406; 3805002; 6742776; 2384686; 1755842; 8571955; 8601739; 9649563; 9585598; 11039124; 11753383; 12601550; 16385445; 17875872; 19144952; 18787536; 19744342; 20857522; 21659066; 22971305; 23016163; 23323258; 23600449
FERMT1	15889	55612	Kindler syndrome	AR	Adult		Dermatologic; Oncologic	Dermatologic; Oncologic		Individuals have an increased risk of squamous cell carcinoma and surveillance for premalignant keratoses/early malignancy may allow early diagnosis and treatment	13149722; 8910840; 9301588; 10809978; 12472544; 12668616; 12789646; 17460733; 17854379; 17916195; 17989907; 18410424; 18835760; 19292718; 19945624; 21336475; 21936020 
FERMT3	23151	83706	Leukocyte adhesion deficiency, type III	AR	Pediatric		Allergy/Immunology/Infectious; Hematologic	Allergy/Immunology/Infectious; Hematologic		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals may have hematologic anomalies, and treatment (which may include RBC and platelet transfusions) may be indicated; BMT has been described	9312170; 12595312; 17185466; 19234460; 19064721; 20357244; 21441448
FEZF1	22788	389549	Hypogonadotropic hypogonadism 22 with or without anosmia	AR	Pediatric		Endocrine; Neurologic	Endocrine		In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	25192046
FGA	3661	2243	Afibrinogenemia, congenital; Dysfibrinogenemia, congenital; Hypodysfibrinogenemia, congenital; Familial visceral amyloidosis	AD/AR	Pediatric		Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Renal	Cardiovascular; Gastrointestinal; Hematologic; Pharmacogenomic	Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	Individuals with afibrinogenemia/dysfibrinogenemia are at risk of a variety of bleeding diatheses; Preventive or treatment-based (eg, with fibrinogen in the case of congenital afibrinogenemia) measures may be beneficial; Individuals with Familial amyloidosis may be at risk of cardiovascular complications, including arrhythmia, and surveillance may allow prompt detection and management;  The treatment of amyloidosis differs depending on the genetic cause (genetic diagnosis may additionally help avoid relatively high-risk treatment regimens), and in fibrinogen-related amyloidosis, liver transplantation may be beneficial	5645286; 7298640; 6191801; 4052020; 3726812; 3618591; 3590111; 3345340; 2133234; 1675636; 2070049; 1391954; 1634621; 8097946; 8140431; 8473507; 8113408; 8675656; 8639778; 9389696; 9916133; 10891444; 10910940; 11739173; 11159525; 12050338; 12358944; 14615374; 15489905; 16362348; 18500534; 20806111; 21245743; 22732251; 22795623 
FGB	3662	2244	Afibrinogenemia, congenital; Dysfibrinogenemia, congenital; Hypodysfibrinogenemia, congenital	AD/AR	Pediatric		Hematologic	Hematologic		Individuals with afibrinogenemia/dysfibrinogenemia are at risk of a variety of bleeding diatheses; preventive or treatment-based (eg, with fibrinogen in the case of congenital afibrinogenemia) may be beneficial	3156856; 2885451; 3388290; 2018836; 1565641; 1634610; 9185528; 10666208; 11468164; 11425767; 12393540; 15070683; 18853456; 21301788; 22955321 
FGD1	3663	2245	Aarskog-Scott syndrome; Mental retardation, X-linked syndromic 16	XL	N/A	N/A	Craniofacial; Genitourinary; Musculoskeletal; Neurologic	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5504078; 5173168; 7954831; 10930571; 11093277; 15809997; 17152066; 17847065; 19110080; 20082460; 21654724; 21739585; 22876573 
FGD4	19125	121512	Charcot-Marie-Tooth disease, type 4H	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15744041; 17564959; 17564972; 19221294; 19332693; 20301641; 21840889; 22734899 
FGF10	3666	2255	Lacrimoauriculodentodigital syndrome	AD	Pediatric	Allelic with Aplasia of lacrimal and salivary glands (AD)	Audiologic/Otolaryngologic; Dental; Endocrine; Musculoskeletal	Audiologic/Otolaryngologic	Lacrimoauriculodentodigital syndrome may be clinically recognizable by a number of manifestations, including outer ear anomalies	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	15654336; 16501574; 16630169; 17213838
FGF14	3671	2259	Spinocerebellar ataxia 27	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12489043; 15470364; 21600715
FGF16	3672	8823	Metacarpal 4-5 fusion	XL	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23709756; 24878828
FGF17	3673	8822	Hypogonadotropic hypogonadism 20, with or without anosmia	AD/Multigenic	Pediatric		Craniofacial; Endocrine; Musculoskeletal; Neurologic	Endocrine	Relatively complex genetic models of disease have been described (eg, involving mutations in other FGF8-network-associated genes)	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	6881209; 23643382
FGF20	3677	26281	Renal hypodysplasia/aplasia 2	AR	N/A	N/A	Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22698282
FGF23	3680	8074	Hypophosphatemic rickets, autosomal dominant; Tumoral calcinosis, hyperphosphatemic	AD/AR	Pediatric		Dental; Renal; Musculoskeletal	Renal		In Hypophosphatemic rickets, autosomal dominant, treatment with both phosphate and high-dose vitamin D can be effective; In Tumoral calcinosis, hyperphosphatemic, phosphate reduction (eg, with dietary means and phosphate-binding agents) can be beneficial	5925614; 5173181; 4538804; 4353218; 3659264; 2777854; 1353055; 9024275; 11062477; 12541190; 15590700 
FGF3	3681	2248	Deafness, congenital with inner ear agenesis, microtia, and microdontia	AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Dental	Audiologic/Otolaryngologic	The condition may typically be recognizable from physical examination	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	17236138; 18435799; 18701883; 21480479
FGF5	3683	2250	Trichomegaly	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24989505
FGF8	3686	2253	Hypogonadotropic hypogonadism 6, with or without anosmia	AD/Digenic	Pediatric	Allelic with Holoprosencephaly (AD)	Craniofacial; Dental; Endocrine; Musculoskeletal; Neurologic	Endocrine	Relatively complex patterns of inheritance (eg, involving mutations in FGFR1) have been described	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	18596921; 21045958; 21832120; 20301509; 21976454; 22319038 
FGF9	3687	2254	Multiple synostoses syndrome 3	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19589401
FGFR1	3688	2260	Hypogonadotropic hypogonadism 2 with or without anosmia; Trigonocephaly 1; Jackson-Weiss syndrome; Pfeiffer syndrome	AD/Digenic/Multigenic	Pediatric	Allelic with Hartsfield syndrome (AD/AR); Osteoglophonic dysplasia (AD)	Audiologic/Otolaryngologic; Craniofacial; Dental; Endocrine; Genitourinary; Musculoskeletal; Neurologic	Audiologic/Otolaryngologic; Endocrine	Complex inheritance models, such as inolving digenic inheritance/synergistic effects (eg, with GNRHR, NELF, as well as other FGF8-network associated genes) has been reported	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required; Some individuals with FGFR1 mutations may have hearing loss, and appropriate interventions may be beneficial as relates to language and speech development	14316612; 7422392; 6881209; 7874169; 8939381; 9475589; 11173846; 10861678; 11420131; 11297579; 2627230; 14564217; 16418210; 15625620; 16470795; 16606836; 17959774; 17360555; 20301509; 17235395; 22035731; 21700882; 23643382; 23812909
FGFR2	3689	2263	Lacrimoauriculodentodigital syndrome; Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis; Sraniofacial-skeletal-dermatological dysplasia; Crouzon syndrome; Jackson-Weiss syndrome; Pfeiffer syndrome; Apert syndrome; Beare-Stevenson cutis gyrata syndrome	AD	Pediatric	Allelic with Bent bone dysplasia syndrome (AD); Scaphocephaly, maxillary retrusion, and mental retardation (AD)	Audiologic/Otolaryngologic; Craniofacial; Dental; Musculoskeletal; Neurologic	Audiologic/Otolaryngologic	FGFR2-related craniosynostosis can include deafness, and may be clinically recognizable, including by outer ear malformations	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	13801313; 5781468; 1271196; 660365; 1519658; 7874170; 7987400; 7674004; 7719333; 8528214; 7719345; 7795583; 7719344; 8644708; 8673103; 8696350; 8683284; 8651276; 9002682; 9150725; 9605588; 9714439; 9664610; 9585583; 9475590; 9475591; 10076886; 10076887; 10067911; 9973282; 10712195; 10951518; 10945669; 10633130; 10735635; 11343323; 12400058; 12900791; 15996217; 15793702; 16440883; 16061565; 16969861; 16876521; 16691624; 16501574; 17529973; 18247426; 19610084; 22387015
FGFR3	3690	2261	Camptodactyly, tall stature, and hearing loss (CATSHL) syndrome; Crouzon syndrome with acanthosis nigricans; Muenke syndrome	AD/AR	Pediatric	Allelic with Thanatophoric dysplasia, type I (AD), Thanatophoric dysplasia, type II (AD); Severe achondroplasia with developmental delay and acanthosis nigricans (AD); Lacrimoauriculodentodigital syndrome (which may be recognizable from multisystem involvement) (AD); Hypochondroplasia (AD); Achondroplasia (AD); Homozygous/compound heterozygous mutations have been described	Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Musculoskeletal; Neurologic	Audiologic/Otolaryngologic	Certain mutations in FGFR3 (such as result in CATSHL or Muenke syndrome) can result in congenital hearing loss, and the  condition may not be recognized early	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	5783850; 4697848; 474637; 3631079; 2650599; 7968151; 8078586; 7913883; 7847369; 7670477; 7493034; 7758520; 7773297; 8589699; 7647778 ; 8585566; 8841188; 8845844; 8923856; 8834055; 8880573; 9279764; 9042914; 9842995; 9600744; 9580776; 3631079; 9279753; 3228140; 9525367; 9733026; 9585583; 9450868; 9797588; 9677066; 10360402; 10360393; 10360392; 10053006; 11055896; 11186939; 10777366; 12116251; 15517832; 16912704; 15241680; 16353253; 16501574; 16411219; 17033969 18000976; 17935505; 17764078; 18000903; 17360555; 17879967; 17895900; 18266238; 18000903; 19449410; 20301540; 20624921; 9842995; 20301588; 19215249; 21204234; 20301331; 20301628; 21403557; 21403567; 22038757; 21971908; 22085076; 22446440; 22565872; 23044018; 23378035; 24168007; 24864036
FGG	3694	2266	Afibrinogenemia, congenital; Dysfibrinogenemia, congenital; Hypodysfibrinogenemia, congenital; Hypodysfibrinogenemia	AD/AR	Pediatric		Hematologic	Hematologic		Individuals with afibrinogenemia/dysfibrinogenemia are at risk of a variety of bleeding diatheses; preventive or treatment-based (eg, with fibrinogen in the case of congenital afibrinogenemia) may be beneficial	4956920; 4427684; 6886002; 4002201; 3563970; 3708159; 3742050; 3337908; 2617471; 2496144; 2257302; 2328317; 7635941; 9746756; 2971042; 2971046; 2738036; 2819242; 2071611; 1471077; 1733971; 8470043; 7740487; 8822581; 9368024; 11001902; 11071644; 11001903; 11435303; 11986213; 17854317; 18832913; 19551918; 20135062; 20580695; 20589319; 20978265
FH	3700	2271	Hereditary leiomyomatosis and renal cell cancer	AD	Pediatric	Allelic with Fumarase deficiency (AR)	Biochemical; Dermatologic; Neurologic; Obstetric; Oncologic	Obstetric; Oncologic		Regular surveillance for dermatologic and uterine neoplasms can be beneficial in order to allow early detection and treatment (which can include medical management and/or surgical excision); Surveillance for renal neoplasms can allow early detection and treatment, which may include total nephrectomy	13520698; 6616883; 3736629; 3807970; 8200987; 11248088; 11865300; 16757530; 15937070; 20301430; 20618355; 21398687; 21404119; 22069215; 23320739; 23254734; 23612258; 23652956; 24346898
FHL1	3702	2273	Myopathy, reducing body, X-linked, childhood-onset; Myopathy, reducing body, X-linked, severe early-onset; Emery-Dreifuss muscular dystrophy 6, X-linked; Myopathy, X-linked, with postural muscle atrophy 	XL	Pediatric	Allelic with Scapuloperoneal myopathy, X-linked dominant (XL)	Cardiovascular; Musculoskeletal	Cardiovascular	In reducing body myopathy, dilated cardiomyopathy has been described, but well after clinical onset; In Myopathy with postural muscle atrophy and Emery-Dreifuss muscular dystrophy 6, heart failure can be deadly, perhaps related to hypertrophic cardiomyopathy; In Emery-Dreifuss muscular dystrophy 6, arrhythmias have been desribed, as well as sudden cardiac death; In all situations, survelliance and early medical management could be beneficial, but the condition may not be easily clinically recognizable	Surveillance for cardiovascular disease (eg, cardiomyopathy, arrhythmias)  and early medical treatment may reduce morbidity	4250729; 7722535; 8619529; 16919903; 18179901; 18952429; 18274675; 18179888;  19716112; 19181672; 19687455; 19171836; 20186852
FIG4	16873	9896	Amyotrophic lateral sclerosis 11; Charcot-Marie Tooth disease, autosomal recessive, type 4J; Polymicrogyria, bilateral occipital	AD/AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17572665; 18758830; 19118816; 21705420; 24598713; 24878229
FIGLA	24669	344018	Premature ovarian failure 6	AD	Pediatric		Endocrine; Obstetric	Obstetric		Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency	18499083
FKBP10	18169	60681	Osteogenesis imperfecta, type XI; Bruck syndrome	AR	N/A	N/A	Dental; Musculoskeletal	General	Bisphosphonates may reduce fracture frequency, but it is unclear if early (genomic) diagnosis would be additionally beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20362275; 20696291; 20839288; 21567934
FKBP14	18625	55033	Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss	AR	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Genitourinary; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	Cardiovascular		Cardiovascular complications, including aortic rupture, have been described, and awareness and surveillance may allow rapid diagnosis and treatment, which may ameliorate morbidity and mortality	22265013; 24773188
FKRP	17997	79147	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5; Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B, 5; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5	AR	Pediatric		Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	Cardiovascular		Individuals have been described with cardiovascular complications (eg, left-ventricular dysfunction), and recognition may allow surveillance (eg, with echocardiogram) and early medical management aimed at optimizing cardiac function; Cardiac transplantation has been described	9577386; 10838249; 11592034; 11320179; 11741828; 12707425; 14647208; 15121789; 14523375; 15580560; 16634037; 16476814; 17336067; 18060779; 18639457; 18671187; 19705481; 19917824; 20301582; 20627570
FKTN	3622	2218	Cardiomyopathy, dilated, 1X; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4; Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4	AD/AR	Pediatric		Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	Cardiovascular; Musculoskeletal		Surveillance for cardiovascular complications may allow early diagnosis and treatment, which may ameliorate morbidity and mortality; Cardiomyopathy, dilated, 1X has been reported as being treated with transplant; Individuals with Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4 has been reported as benefiting from treatment with steroids	7258547; 8124873; 9690476; 10545611; 10817652; 12601708; 17036286; 17044012;  17878207; 18177472; 19015585; 19342235; 19299310; 19179078; 19842201; 20627570; 20961758 
FLCN	27310	201163	Birt-Hogg-Dube syndrome; Pneumothorax, primary spontaneous 	AD	Adult		Dermatologic; Oncologic; Pulmonary	Oncologic; Pulmonary		Individuals are at risk for a number of types of neoplasms, and surveillance and early diagnosis/treatment may be beneficial; Some individuals may demonstrate isolated pneumothorax, but may be at elevated risk for malignancies; Affected individuals commonly have recurrent pneumothoraces, and early pleurodesis may beneficial)	596896; 10522666; 11533913; 12471204; 12204536; 15657874; 15852235; 17496196; 18505456; 18234728; 19320655; 20413710; 20618353; 22146830; 23264078; 23414156; 23542717; 23715758; 23846428; 23995526
FLG	3748	2312	Icthyosis vulgaris	AD/AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12473059; 12838398; 17030239; 16550169; 16444271; 16815158; 17291859; 21692775; 21712002; 21790526; 22299762; 22951058; 22962861; 22989708 
FLI1	3749	2313	Thrombocytopenia, Paris-Trousseau type	AD	Pediatric		Hematologic	Hematologic	Individuals with genomic deletions including FLI1 have been reported with thrombocytopenia, but the evidence for involvement of this gene in the phenotype is unclear	Individuals may have bleeding tendency, and precautions (eg, in surgical situations) may be beneficial	14597985; 22887642 
FLNA	3754	2316	Cardiac valvular dysplasia, X-linked; Heterotopia, periventricular, Ehlers-Danlos variant;  Intestinal pseudoobstruction, neuronal, X-linked/Congenital short bowel syndrome	XL	Pediatric	Allelic with Dysmorphic facies with multi-organ anomalies (XL); FG syndrome 2 (XL); Frontometaphyseal dysplasia (XL); Melnick-Needles syndrome (XL);  Otopalatodigital syndrome, type I (XL); Otopalatodigital syndrome, type II (XL); Periventricular nodular heterotopia (XL); Terminal osseus dysplasia (XL)	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Pulmonary; Renal	Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal		In Cardiac valvular dysplasia, X-linked, surveillance for and correction of valvular anomalies can be beneficial; Individuals with Heterotopia, periventricular, Ehlers-Danlos variant may have cardiac and vascular anomalies, which may warrant surveillance and medical/surgical management; For hearing loss, early recognition may allow beneficial interventions that can help with speech and language development; In Intestinal pseudoobstruction, neuronal, X-linked/Congenital short bowel syndrome, individuals have been described as benefiting from early introduction of enteral feeds, with later weaning from parenteral nutrition, and awareness of the risk of other GI-related complications may allow prompt recognition and management	5938049; 5807657; 8230166; 8290091; 8644737; 9883725; 9800904; 9497244; 10982965; 11857561; 11914408; 12612583; 15249610; 14988809; 15864382; 15940695; 15654694; 15523633; 15917206; 15654694; 15668422; 16299064; 16538226; 16596676; 16926860; 17152064; 17190868; 17264970; 17357080;  17431908; 17632775; 18209785; 18427995; 18854860; 19917821; 20301567; 20014127; 20598277; 20730588; 20888935; 21031081; 21194575; 21412975; 21484998; 21815255; 21960593; 22238415; 22366253; 22740120; 23037936; 23873601
FLNB	3755	2317	Larsen syndrome; Spondylocarpotarsal synostosis syndrome; Boomerang dysplasia; Atelosteogenesis, type I; Atelosteogenesis, type III	AD/AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal	Audiologic/Otolaryngologic; Musculoskeletal		Surveillance and early intervention related to cervical spine stability can allow early detection and treatment of manifestations; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	8609132; 12955767; 14991055; 15994868; 17202879; 16801345; 18257094; 18377309; 18386804; 20301736; 22190451; 22354125 
FLNC	3756	2318	Myopathy, distal, 4; Myopathy, myofibrillar, 5	AD	Adult		Cardiovascular; Musculoskeletal	Cardiovascular		Some affected individuals have been described with cardiomyopathy, and surveillance (eg, including echocardiography an electrocardiography) may allow early diagnosis and management	15929027; 15824355; 19050726; 21620354; 22131542? 22806379; 23109048 
FLRT3	3762	23767	Hypogonadotropic hypogonadism 21, with or without anosmia	AD/Digenic/Multigenic	Pediatric		Audiologic/Otolaryngologic; Endocrine; Musculoskeletal; Neurologic	Endocrine	Relatively complex genetic models of disease have been described (eg, involving mutations in other FGF8-network-associated genes)	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	6881209; 23643382
FLT4	3767	2324	Lymphedema, hereditary I (Milory disease)	AD/AR	Pediatric		Allergy/Immunology/Infectious; Cardiovascular	Allergy/Immunology/Infectious	Biallelic inheritance has been described	Treatment includes early and aggressive treatment of infections, as well as prophylactic antibiotics in some instances	14295660; 9817924; 10835628; 12960217; 15689446; 16965327; 16924388; 19002718; 19289394; 20301417; 22768468 
FLVCR1	24682	28982	Ataxia, posterior column, with retinitis pigmentosa	AR	N/A	N/A	Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9409377; 9855554; 21070897; 21267618; 22279524; 22483575 
FLVCR2	20105	55640	Proliferative vasculopathy and hydraencephaly-hydrocephaly syndrome	AR	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	General		Treatment may involve dietary modification (eg, to restrict trimethylamine precursors), and medical/dietary treatment (eg, with agents such as metronidazole, neomycin,  lactulose, copper chlorphyllin, activated charcoal, (E, E)-2, 4-undecadienal) as well as riboflavin supplementation  (the use of specific pH soaps may be beneficial as well)	7474897; 9398858; 9846928; 10646019; 10485731; 12653714; 12893987; 12938085; 15565078; 16601883; 20301282; 22126753; 23430514
FMO3	3771	2328	Trimethylaminuria	AR	Pediatric		Biochemical	Biochemical		Treatment may involve dietary modification (eg, to restrict trimethylamine precursors), and medical/dietary treatment (eg, with agents such as metronidazole, neomycin,  lactulose, copper chlorphyllin, or activated charcoal) as well as riboflavin supplementation  (the use of specific pH soaps may be beneficial as well)	7474897; 9398858; 9846928; 10646019; 10485731; 12653714; 12893987; 12938085; 15565078; 16601883; 22126753 
FMR1	3775	2332	Premature ovarian failure	XL	Pediatric	Allelic with Fragile X syndrome (XL); Fragile X tremor/ataxia syndrome (XL)	Craniofacial; Endocrine; Neurologic; Obstetric	Obstetric	The conditions frequently involve expanded trinucleotide repeats	Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency	5794013; 7333582; 6958915; 6711591; 3398009; 2195034; 1944467; 9719368; 10208170; 10325264; 11445641; 12730995; 12638084; 12533098; 14747503; 15065016; 15052536; 16043804; 16493202; 17166801; 18348275; 19724010; 19411303; 20228389; 19542082; 21518720; 21188402; 21300345; 21912443 
FN1	3778	2335	Glomerulopathy with fibronectin deposits 2	AD	N/A	N/A	Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1544672; 7747733; 7564073; 12042895; 18268355
FOLR1	3791	2348	Cerebral folate deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		Diagnosis is critical, as the natural history includes severe neurodegeneration and neurologic impairment, and treatment with folinic acid (it is important to note that response to such treatment is better when initiated in early childhood) can reverse symptoms and improve brain abnormalities and function	19732866; 20857335; 21752681; 22586289; 22734130
FOXC1	3800	2296	Peters anomaly; Axenfeld-Rieger syndrome, type 3; Iridogoiodysgenesis, type 1	AD	Adult		Audiologic/Otolaryngologic; Cardiovascular; Musculoskeletal; Ophthalmologic	Cardiovascular; Ophthalmologic; Pharmacogenomic	Severe and difficult to treat glaucoma has been reported in many individuals with Peters anomaly	Individuals with Axenfeld-Rieger anomaly have a high risk of developing glaucoma, but treatment may not be effective in the majority of cases; Awareness of cardiac anomalies (eg, valvular anomalies leading to congestive heart failure have been described) may allow early detection and treatment; Agents that may contribute to glaucoma should be avoided	9445211; 9792859; 9620769; 11004268; 11007653; 10713890; 12036988; 11170889; 12036988; 12614756; 12614756; 17197537; 18498376; 19668217; 19793056; 23239455 
FOXC2	3801	2303	Lymphedema-distichiasis syndrome	AD	N/A	N/A	Cardiovascular; Dermatologic; Musculoskeletal; Ophthalmologic	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14269895; 3573000; 10086462; 11078474; 11499682; 11694548; 12485195; 12114478; 15523639; 17372167; 19760751; 20186799; 20301630; 20450314; 20552815; 21918810; 22349027; 22768468 
FOXE1	3806	2304	Hypothyroidism, thyroidal, with spiky hair and cleft palate (Bamforth-Lazarus syndrome); Congenital hypothyroidism	AR	Pediatric		Craniofacial; Dermatologic; Endocrine; Musculoskeletal	Endocrine		Though the condition may be clinically recognizable, recognition and prompt treatment of hypothyroidism can be beneficial	2918525; 8320710; 9697705; 12165566; 16882747; 17717707; 17318017; 19779022; 20484477; 20453517; 20094846; 21981779; 21311165
FOXE3	3808	2301	Aphakia, congenital primary; Anterior segment mesenchymal dysgenesis	AR/AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3550563; 11159941; 16826526; 21150893
FOXF1	3809	2294	Alveolar capillary dysplasia with misalignment of pulmonary veins	AD	N/A	N/A	Cardiovascular; Genitourinary; Gastrointestinal; Musculoskeletal; Pulmonary	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15520767; 19500772; 20425831; 22990143; 23407133; 23444129; 23505205; 24842713
FOXG1	3811	2290	Rett syndrome, congenital variant	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18571142; 19578037; 19564653; 20736978; 21441262; 21536641; 21910242; 21953941; 22091895; 22129046; 22258524; 22415763; 22670136 
FOXH1	3814	8928	Holoprosencephaly; Congenital heart malformations	AD	N/A	N/A	Cardiovascular; Craniofacial; Endocrine; Neurologic	General	Individuals with holoprosencephaly  may demonstrate endocrine anomalies, including diabetes insipidus	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18538293
FOXI1	3815	2299	Enlarged vestibular aqueduct; Pendred syndrome	AD	Pediatric		Audiologic/Otolaryngologic; Endocrine	Audiologic/Otolaryngologic; Endocrine	Digenic inheritance (with SLC26A4) has been reported	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Pendred syndrome, awareness of the potential for thyroid abnormalities may be beneficial to allow early detection and appropriate management	17503324
FOXL2	1092	668	Blepharophimosis, epicanthus inversus, and ptosis, type 1; Blepharophimosis, epicanthus inversus, and ptosis, type 2; Premature ovarian failure 3	AD	Pediatric		Craniofacial; Endocrine; Genitourinary; Obstetric; Ophthalmologic	Obstetric		Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency (which is also reported in women with BPES)	11175783; 12149404; 15962237; 16283882; 17089161; 19429596; 21325395
FOXN1	12765	8456	T-cell immunodeficiency, congenital alopecia, and nail dystrophy	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic	Allergy/Immunology/Infectious	Heterozygous mutations may result in milder manifestations; In recessive disease, neuroanatomical malformations have been described	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported	8911612; 10206641; 15180707; 18339010; 20429426; 20864124; 21507891 
FOXP1	3823	27086	Mental retardation with language impairment and autistic features	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20571508; 20950788; 21572417; 22521361 
FOXP2	13875	93986	Speech-language disorder 1	AD	N/A	N/A	Musculoskeletal; Neurologic	General	Paternal deletions are associated with Russell-Silver syndrome, and may be related to speech-language involvement in the condition	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3265313; 11586359; 15326624; 15877281; 17033973; 16470794; 20301499; 22106036; 22105961; 22144704 
FOXP3	6106	50943	Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked (IPEX)	XL	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Renal	Allergy/Immunology/Infectious	The condition may involve infectious and autoimmune manifestations	For neutropenia, G-CSF can be effective; Bone marrow transplantation has been reported as effective if performed early; Prophylactic antibiotics can be beneficial; Immunosuppressive agents may be helpful	7040622; 2246696; 8482279; 8777684; 11120765; 11396442; 11137993; 11295725; 11137992; 20301297; 20842625; 21979562; 21741320; 21865090; 22132891; 23534934
FOXRED1	26927	55572	Mitochondrial complex I deficiency; Leigh syndrome	AR	N/A	N/A	Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial, and surveillance for cardiac involvement may be beneficial in order to allow early management	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 20818383; 20858599
FRAS1	19185	80144	Fraser syndrome	AR	N/A	N/A	Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12766769; 16894541; 17163535; 18671281; 22029163 
FREM1	23399	158326	Bifid nose with or without anorectal and renal anomalies; Trigonocephaly 2; Manitoba oculotrichoanal syndrome; Congenital diaphragmatic hernia, autosomal recessive	AD/AR	N/A	N/A	Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Ophthalmologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1554017; 11332973; 11822703; 17352387; 19732862; 21507892; 21931569; 23112756; 23221805 
FREM2	25396	341640	Fraser syndrome	AR	N/A	N/A	Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15838507; 18203166; 18000968; 18671281
FRMD7	8079	90167	Nystagmus, infantile periodic alternating, X-linked	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16020310; 16240070; 17013395; 18087240; 17768376; 19072571; 17962394; 21746984; 21303855; 21386928; 21746984; 22065930; 22262942; 22490987 
FSCN2	3960	25794	Retinitis pigmentosa 30	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11527955
FSHB	3964	2488	Follicle-stimulating hormone deficiency, isolated	AR	Pediatric		Endocrine; Obstetric	Endocrine; Obstetric		Hormonal treatment (eg, with FSH) can allow induction of ovulation and fertility	4344039; 758600; 8220432; 9280841; 17961559 
FSHMD1A	3966	2489	Facioscapulohumeral muscular dystrophy 1A	AD/AR	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Musculoskeletal; Ophthalmologic	Cardiovascular; Ophthalmologic		Awareness and surveillance of cardiac manifestations, including arrhythmias (eg, with EKG), may allow early treatment, which may ameliorate morbidity and mortality; Individuals may present with ophthalmologic anomalies (including retinal telangiectasia, which may rarely progress to Coats disease), and recognition may allow surveillance and prompt management	15411118; 6704043; 6745940; 3580827; 1927871; 1363881; 7987304; 9506542; 10631134; 14557558; 15154112; 16178028; 17229919; 17563001; 20301616; 21984394; 22217918; 22482803
FSHR	3969	2492	Ovarian hyperstimulation syndrome; Ovarian dysgenesis 1	AD/AR	Pediatric		Endocrine; Genitourinary; Obstetric	Obstetric		In Ovarian hyperstimulation syndrome, diagnosis may be beneficial for preconception/reproductive planning (eg, in order to avoid precipitating factors related to ovarian hyperstimulation); In Ovarian dysgenesis 1, genetic knowledge may be beneficial to allow Interventions such as preserving eggs in women with premature ovarian insufficiency	7553856; 9769327; 12498425; 11889179; 12930928; 12930927; 12930924; 17721928; 20087398
FTCD	3974	10841	Glutamate formiminotransferase deficiency	AR	N/A	N/A	Biochemical	General	Early descriptions included benefits of folic acid treatment, but later descriptions call this into question, and the clinical consequences of the deficiency are unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5897668; 5956503; 4413489; 235753; 1272625; 12815595; 22108709 
FTH1	3976	2495	Hemochromatosis, type 5	AD	Pediatric		Hematologic	Hematologic		Preventive measures to ameliorate iron overload may be beneficial	11389486
FTL	3999	2512	L-ferritin deficiency; Neurodegeneration with brain iron accumulation 3; Hyperferritinemia-cataract syndrome	AD/AR	N/A	N/A	Hematologic; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7493028; 8558554; 7669675; 11438811; 11703332; 12200611; 12199804; 12746423; 15173247; 15280904; 15099026; 17142829; 18413574; 18854324; 20301320; 22020773; 22278127 ; 22515742; 23940258
FTO	24678	79068	Growth retardation, developmental delay, coarse facies, and early death	AR	N/A	N/A	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19559399
FTSJ1	13254	24140	Mental retardation, X-linked 9	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8288232; 10398246; 12239714; 15162322; 15342698; 18081026 
FUCA1	4006	2517	Fucosidosis	AR	N/A	N/A	Biochemical; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4172303; 4241464; 4247654; 5026163; 1214294; 4128078; 7460371; 6538300; 2903667; 3409541; 2642067; 2012122; 8719750; 9039984; 9762612; 10094192; 12408193; 17427030; 18504684 
FUS	4010	2521	Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia; Essential tremor	AD/AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12840784; 12858291; 19741216; 19251627; 19741215; 19251628; 19861302; 20385912; 20577002; 20660363; 20668259; 22863194; 22980027; 22999566; 23046859 
FUT1	4012	2523	Bombay phenotype; Para-Bombay phenotype; H-deficient blood group; Reunion variant	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	14918471; 13269394; 13767673; 5763629; 7246545; 7180848; 6177241; 6859043; 2118655; 7912436; 9299444
FUT3	4014	2525	Blood group, Lewis	AD	Pediatric		Hematologic	Hematologic		Variants may be associated with a blood group may be important in specific situations (eg, related to transfusion)	2922027; 7961897; 8943285; 9703429; 11668626; 15383031 
FUT6	4017	2528	Fucosyltransferase 6 deficiency	AR	N/A	N/A	Biochemical	General		Clinical relevance is unclear	8175676
FUZ	26219	80199	Neural tube defects, susceptibility to	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21840926
FXN	3951	2395	Friedreich ataxia	AR	Pediatric		Cardiovascular; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic	Cardiovascular	The conditions frequently involve expanded trinucleotide repeats	Though frequently clinically recognizable, the majority of individuals have cardiomyopathy,  and medications (eg, antiarrhythmics, medications for cardiac-failure, anticoagulants, and pacemaker insertion) may be beneficial; Heart transplantation has been described	13872187; 5673214; 5533984; 4206197; 7272714; 6231891; 8057123; 7695235; 8596916; 8623752; 8815938; 8751856; 9150176; 9142000; 9245990; 9259271; 9539351; 10399865; 10543403; 10533031; 10500204; 11425956; 11843702; 11857753; 15539131; 19347027; 20301458; 21700145; 21570254; 22409940; 22522441; 22691228; 22752483; 22752493; 22764179; 23196337; 23242090
FXYD2	4026	486	Hypomagnesemia 2, renal	AD	Pediatric		Renal	Renal		Surveillance for and treatment of electrolyte abnormalities can be beneficial (eg, to avoid sequelae such as pseudogout, as has been described in affected individuals)	3298795; 11062458 
FYCO1	14673	79443	Cataract, autosomal recessive congenital 2	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11519376; 21636066
FZD4	4042	8322	Exudative vitreoretinopathy; Retinopathy of prematurity	AD/Digenic	N/A	N/A	Ophthalmologic	General	Digenic inheritance (with LRP5 has been reported)	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12172548; 14507768; 15488808; 15981244; 21097938 
FZD6	4044	8323	Nail disorder, nonsyndromic noncongenital 10	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21665003
G6PC	4056	2538	Glycogen storage disease Ia	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Oncologic; Renal	Biochemical; Gastrointestinal; Oncologic; Renal		Dietary measures can be beneficial allow optimal glucose levels and promote growth and development (additionally, specific carbohydrate sources should be limited); Allopurinol to prevent gout and lipid-lowering medications to prevent hyperlipidemia may be necessary when dietary therapy is ineffective; Citrate supplementation and ACE inhibitors may help prevent development of decrease renal complications, though renal transplant may ultimately be necessary; Surveillance for and treatment of hepatic neoplasms (including liver transplant in some) can be beneficial  	5240134; 4302545; 204806; 204758; 6928317; 6581385; 2883397; 3030527; 3422104; 2199830; 2109144; 1743219; 8391447; 8211187; 8448918; 8319728; 8441093; 8319729; 8319726 ; 8203427; 8273986; 7668282; 7573034; 8733042; 8758135; 9427147; 9332655; 10472532; 10070617; 10748407; 11241046; 11757580; 15151508; 19762333; 20301489; 20720360; 21058447; 21481415; 21620082 
G6PC3	24861	92579	Neutropenia, severe congenital, 4, autosomal recessive; Dursun syndrome	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Hematologic; Neurologic; Renal	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Genitourinary; Hematologic		Antiinfectious prophylaxis (including with G-CSF) and early and aggressive treatment of infections may be beneficial; Awareness of other manifestations, including affecting the cardiac, endocrine, and urogenital systems may allow early diagnosis and treatment	19696212; 19118303; 20799326; 20616219; 20717171; 21285905; 22050868 
G6PD	4057	2539	Glucose-6-phosphate dehydrogenase deficiency	XL	Pediatric		Allergy/Immunology/Infectious; Hematologic	Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic	The condition involves predisposition to anemia, which can be precipitated by, among other things, certain medications; Complete G6PD deficiency can result in chronic granulamotous disease secondary to neutrophil deficiency	Hemolytic reactions can result from a variety of triggers, such as infections, dietary items, and medications, and avoidance of precipitating agents (or redosing in order to decreased the chance of certain medication reactions, as well as prompt removal in the case of a reaction) can be beneficial; Individuals are also susceptible to neonatal jaundice; Complete G6PD deficiency can result in immunodeficiency, and prophylactic measures, as well as prompt and aggressive treatment of infections, can be beneficial	13360274; 13500095; 14014720; 14158057; 4388132; 5369703; 5305539; 4401271; 4125296; 5448; 3681550; 3446582; 2836867; 2912069; 2910917; 2602358; 2248331; 2263506; 2157298; 2321910; 1999409; 2005960; 1303182; 1611091; 1551674;  1536798; 1562739; 8471773; 8490627; 8364584; 7949118; 8533762; 7617034; 8627445; 8807322; 8826878; 8579052; 8956035; 9427729; 9674740; 10666231; 11048840; 11433050; 11803413; 11857737; 12028056; 15349799; 16204390; 15724035; 16155737; 16493607; 16607506; 16528451; 17444323; 18177777; 19112496; 18379570; 19177059; 20007901; 20701405; 21641489; 22573495; 22795224; 23237606; 23384623; 23573906; 23714236; 23815264; 23834949; 23860572; 23874116; 23874768
GAA	4065	2548	Glycogen storage disease II	AR	Pediatric		Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Pulmonary	Biochemical; Cardiovascular; Pharmacogenomic		Enzyme therapy is available; Disease-specific care of cardiomyopathy may be beneficial (eg, some standard drugs are contraindicated, and there is high  risk for arrhythmias and sudden cardiac death)	5217754; 4288232; 5229488; 5247277; 5240358; 6810200; 6401355; 3084996; 3093639; 3090917; 3322184; 3135192; 3282727; 3288378; 2403755; 2243227; 2203258; 1895140; 11071489; 10931430; 11286229; 12601120; 12897283; 15668445; 15985590; 16433701; 17190962; 16917947; 19047571; 19047572; 20301438; 21543987; 21518733; 21637107; 22253258; 22334186; 22353292; 22365055; 22492103; 22538254; 22539577; 22581536; 22616199; 23884227; 24008937; 24011652; 24044919
GABRA1	4075	2554	Epilepsy, juvenile myoclonic, susceptibility to, 5; Epilepsy, childhood absence, susceptibility to, 4; Epileptic encephalopathy, early infantile 19	AD	N/A	N/A	Neurologic	General	As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11992121; 16718694; 20551311; 24623842
GABRB3	4083	2562	Epilepsy, childhood absence, susceptibility to, 5	AD	N/A	N/A	Neurologic	General	As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12189488; 11920158; 11810291; 16835263; 17957331; 18514161; 22303015 
GABRG2	4087	2566	Dravet syndrome; Generalized epilepsy with febrile seizures plus, type 3; Familial febrile seizures 8; Epilepsy, childhood absence, susceptibility to, 2	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Many variants may involve a susceptibility locus and/or evidence or clinical applicability is unclear	11326274; 11326275; 1748509; 12117362; 17190949; 19261880; 20308251; 23069679
GAD1	4092	2571	Cerebral palsy, spastic quadriplegic, 1	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9084927; 15571623
GALC	4115	2581	Krabbe disease	AR	Pediatric		Biochemical; Neurologic	Biochemical		BMT/HSCT have been described, and in presymptomatic infants as well as older mildly-affected individuals, this treatment may improve and preserve cognitive function (ie, presymptomatic transplant has much better neurological outcomes)	14024503; 3123790; 4773865; 1817026; 1817027; 2056315; 1891085; 8297359; 7581365; 9449482; 8940268; 9338580; 9545360; 10833326; 15901860; 16607461; 17579360; 19332366; 21070211; 20301416; 20886637; 22115770; 22704718; 23462331; 23276707
GALE	4116	2582	Galactose epimerase deficiency	AR	Pediatric		Biochemical; Gastrointestinal; Neurologic; Ophthalmologic; Renal	Biochemical; Neurologic		The generalized form, which typically manifests clinically in infancy upon exposure to lactose-containing diet, can result in lethal sequelae, and can be treated or prevented through dietary means (galactose/lactose restriction); Though data are unclear, individuals with intermediate forms of disease may also benefit from galactose restriction as well	4644860; 4785150; 404274; 7305435; 7227386; 6408303; 3948246; 9700591; 3141714; 8295413; 9326324; 9700591; 9538513; 9973283; 10086948; 11117433; 14970742; 15639193; 16301867; 16302980; 16385452; 18188677; 19250319; 19904445; 20725869; 21290786; 23430501
GALK1	4118	2584	Galactokinase deficiency	AR	Pediatric		Biochemical; Neurologic; Ophthalmologic	Biochemical		Individuals may manifest with early-onset cataracts, and dietary measures (galactose/lactose restricted diet) can be effective; The presence of pseudotumor cerebri has been described, and awareness may allow prompt recognition and management	3043741; 5109408; 5034870; 74495; 490246; 7670469; 8908517; 10570908; 10521295; 10790206; 11139256; 11978884; 12705493; 15024738; 17517531; 20405025; 21290184; 22154682; 22632133
GALNS	4122	2588	Mucopolysaccharidosis IVA (Morquio syndrome A)	AR	Pediatric	N/A	Biochemical; Dental; Musculoskeletal; Ophthalmologic; Pulmonary	Cardiovascular; Musculoskeletal; Ophthalmologic; Pulmonary		The condition may involve cardiac manifestations including cardiac valve abnormalities, and awareness may allow surveillance and prompt recognition and treatment (eg, through surgical interventions); As individuals are at risk of injury due to spinal stenosis, awareness may allow appropriate precautions (eg, during surgeries or medical procedures); Awareness of the risk of certain ophthalmological complications (including glaucoma) can allow prompt awareness and treatment; Measures to optimize pulmonary function can be beneficial	770035; 5704829; 17569489; 3129221; 7607677; 8651279; 9298823; 10814710; 16287098; 20574428; 22078177; 22178352; 22231379; 22358740; 22521955; 22976768; 23313879; 23371450; 23385297; 23452954; 23665161; 23844448; 23860310; 23876334
GALNT12	19877	79695	Colorectal cancer, susceptibility to, 1	AD	Adult		Oncologic	Oncologic		Surveillance for colorectal neoplasms may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality	19617566; 22461326 
GALNT3	4125	2591	Tumoral calcinosis, hyperphosphatemic	AR	Pediatric		Dermatologic; Musculoskeletal; Renal	Renal		Individuals may manifest with sequelae (ie, increased calcium phosphate deposition) of hyperphosphatemia due to increased renal phosphate absorption, and phosphate reduction (eg, with dietary means and phosphate-binding agents) can be beneficial, though families for whom treatment was not effective have been reported	3774168; 4538804; 3998061; 3839626; 3659264; 338191; 2777854; 12541190; 15133511; 15599692; 15687324; 16528452; 16528452; 16567474; 16940445; 17129170; 17311862; 17351710; 17853462; 18322299; 18618993; 18982401; 19255228; 20358599; 21347749; 22142751
GALT	4135	2592	Galactosemia	AR	Pediatric		Biochemical; Endocrine; Gastrointestinal; Hematologic; Neurologic; Obstetric; Ophthalmologic; Renal	Biochemical		Although there is some controversy related to treatment of individuals with various enzymatic activities, dietary measures (eg,lactose-free and galactose-restricted diet, with vitamin supplementation aimed to prevent decreased bone mineralization) can be effective	1610789; 1766867; 7927329; 8040766; 8051928; 8112740; 8499924; 8522334; 8956044; 1897530; 1373122; 2011574; 5337683; 4926707; 4136146; 90818; 6290834; 2512439; 1706789; 8444204; 8198125; 7887416; 8692963; 8943248; 8969739; 9012409; 11261429; 10472536; 10424825; 10604151; 12595586; 16838075; 19224951; 19793842; 20075179; 20222886; 20301691; 20978943; 21059483; 21321007; 21735606; 21779791; 22461411; 22483615; 22944367; 23022339
GAMT	4136	2593	Guanidinoacetate methyltransferase deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		Medical (eg, with creatine-monohydrate, L-ornithine, and/or sodium benzoate) as well as dietary (eg, with ornithine supplementation and protein/arginine restriction) has been reported to increase cerebral creatine, resulting in improvement or stabilization of clinical manifestations in all symptomatic individuals	7808840; 8651275; 9386672; 11196109; 15651030; 17171576; 17336114; 19027335; 20301745; 23031365; 24268530
GAN	4137	8139	Giant axonal neuropathy 1, autosomal recessive	AR	N/A	N/A	Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11062483; 11053687; 18595793; 19231187; 20301315; 20949505; 21356581 
GARS	4162	2617	Charcot-Marie-Tooth disease, type 2D; Neuropathy, distal hereditary motor, type V 	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8541851; 8872480; 10732809; 9879677; 12690580; 16769947; 19329989; 20169446; 20301420; 20301462; 22462675; 23279345 
GAS1	4165	2619	Holoprosencephaly 4	AD	N/A	N/A	Craniofacial; Endocrine; Neurologic	General	Individuals with holoprosencephaly  may demonstrate endocrine anomalies, including diabetes insipidus	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20583177; 21842183
GATA1	4170	2623	Thrombocytopenia with beta-thalessemia, X-linked; Anemia, X-linked, without thrombocytopenia; Dyserythropoietic anemia with thrombocytopenia	XL	Pediatric		Hematologic	Hematologic; Pharmacogenomic		Individuals, especially males (though females have been reported with bleeding complications, such as in the postpartum period), may require preventive measures and treatment (eg, with platelet and/or RBC transfusions) related to bleeding diathesis; Certain activities and agents (eg, contact sports and medications such as NSAIDS) should be avoided in some individuals; BMT has been reported	871527; 10700180; 11418466; 11675338; 11809723; 12200364; 17209061; 20301538; 22102271
GATA2	4171	2624	Immunodeficiency 21; Emberger syndrome; Myelodysplastic syndrome; Acute myeloid leukemia, familial; Chronic neutropenia associated with monocytopenia, evolving to myelodysplasia and acute myeloid leukemia	AD	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dermatologic; Hematologic; Oncologic; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Oncologic		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Surveillance for myelodysplastic syndrome and related oncologic processes (eg, acute myeloid leukemia) may allow early diagnosis and treatment, which may reduce morbidity and mortality; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; HSCT has been described	295075; 21765025; 21892162; 21892158; 22147895; 22271902; 23223431; 24227816
GATA3	4172	2625	Hypoparathyroidism, sensorineural deafness, and renal dysplasia	AD	Pediatric		Audiologic/Otolaryngologic; Endocrine; Renal	Audiologic/Otolaryngologic; Endocrine; Renal		Early recognition of electrolyte abnormalitities (eg, hypocalcemia) can allow prompt treatment in order to avoid severe sequelae; Individuals may also have deafness of varying ages of onset, and may benefit from early recognition and treatment of hearing impairment 	10935639; 11389161; 17309062; 19248180; 9253381; 21399899; 21242646; 21834031; 21157112; 21120445 
GATA4	4173	2626	Atrioventricular septal defect 4; Ventricular septal defect 1; Atrial septal defect 2; Testicular anomalies with or without congenital heart disease; Tetralogy of Fallot	AD	Pediatric		Cardiovascular; Genitourinary	Cardiovascular	Some individuals have been described with multiple congenital anomalies (in addition to cardiac anomalies)	Individuals may present with frank, obvious congenital cardiac malformations, but more subtle presentations have also been described, including valvular anomalies and arrhythmias, and surveillance (eg, with electrocardiogram and echocardiogram) may allow early detection and treatment of manifestations	12845333; 15810002; 17643447; 18055909; 18672102; 20347099; 20659440; 21110066; 21220346; 21637914; 22101736; 22552926; 22648249
GATA6	4174	2627	Heart defects, congenital, and other congenital anomalies	AD	Pediatric	Allelic with Atrial septal defect 9 (AD); atrioventricular septal defect 5 (AD); Persistent truncus arteriosus (AD); Tetralogy of Fallot (AD)	Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic	Gastrointestinal	The conditions can involve multiple congenital anomalies; It has been reported that mutations may result in isolated (and later-onset) pancreatic disease, including adult-onset diabetes mellitus, as well as isolated cardiac disease (it has been suggested that mutations may also result in arrhythmias), or a combination of multiple anomalies	The condition may include pancreatic a/hypogenesis, and individuals may manifest neonatally with severe sequelae of endocrine and exocrine pancreatic insufficiency, and prompt detection can allow potentially beneficial management (eg, with insulin treatment and replacement of exocrine pancreatic enzymes)	19666519; 20631719; 20581743; 22158542; 22750565; 22824924; 22962692; 23020118; 23158662; 23223019; 23635550; 23639568; 24385578
GATAD1	29941	57798	Cardiomyopathy, dilated, 2B	AR	Adult		Cardiovascular	Cardiovascular		Surveillance (eg, echocardiography/electocardiography), preventive measures and medical management (including ICD placement) may be helpful to  decrease morbidity and mortality	21965549
GATAD2B	30778	57459	Mental retardation, autosomal dominant, 18	AD	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23033978
GATM	4175	2628	Arginine:glycine amidinotransferase deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical	Treatment with oral creatine has been reported to possibly increase cerebral creatine, resulting in improved cognitive development	Treatment with oral creatine has been reported to possibly increase cerebral creatine, resulting in improved cognitive development	10762163; 11555793; 12468279; 16769397; 20301745; 20682460; 22386973; 23660394
GBA	4177	2629	Gaucher disease	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	Biochemical; Cardiovascular	Variants may also contribute to neurologic conditions such as Parkinson disease	Enzyme replacement (ERT) and substrate reduction therapy (SRT) is available, and can be effective in terms of hematologic, visceral, and skeletal manifestations; In addition to  supportive care (which can include, for example, the need for RBC transfusions), splenectomy may be beneficial related to splenomegaly and thrombocytopenia in individuals for whom ERT/SRT is not available; BMT/HSCT has been reported in certain severe forms of  disease (eg, type 3, which include neurological involvement); D409H homozygosity results in a phenotype involving specific cardiovascular manifestations, and early diagnosis and care of these manifestations may reduce morbidity and mortality	13906837; 4713569; 870871; 7363908; 7138174;  7160406; 6507325; 3732318; 3950849; 2880291; 3385740; 3342593; 3353383; 2464926; 2308952; 2378352; 2023606; 1817041; 1897529; 1333717; 8434610; 8437594; 7475546; 7500785; 8118463; 8544197; 8544959; 7701581; 7942798; 8737974; 9011805; 9040001; 10636167; 10796875; 10649495; 10682310; 10685993; 11359469; 11241475; 11486896; 12133749; 12359135; 12970647; 12752568; 12595585; 14677062; 15525722; 15669682; 15690354; 16199246; 16630170; 15813845; 15734007; 15937077; 16601874; 16790605; 17464953; 17850633; 17878420; 18338393; 18332251; 19067373; 19286695; 19858467; 19846850; 20837857; 20301446; 21502868; 22375149; 22713811; 22916340; 23363328; 23536258; 23570288; 23683771; 23647506
GBA2	18986	57704	Cerebellar ataxia with spasticity, autosomal recessive 	AR	N/A	N/A	Genitourinary; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18332254; 23332916; 23332917
GBE1	4180	2632	Glycogen storage disease IV	AR	Pediatric	Allelic with Adult polyglucosan body disease (AR); Lethal pterygium syndrome, autosomal recessive (AR)	Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic 	Biochemical; Cardiovascular		In some forms of Glycogen storage disease IV, management to decrease morbidity and mortality related to cardiac sequalae may be beneficial; Liver transplant may be beneficial in some individuals	13279125; 5229990; 4502299; 284761; 6579239; 3464425; 3474393; 3162725; 1984162; 1375445; 7683169; 8437594; 8059607; 8494336;  8613547; 8830177; 9851430; 10384399; 10545044; 10449659; 10603098; 10762170; 12913206; 15452297; 15520786; 14755501; 15019703; 16007674; 16528737; 17662246; 17915577; 17994551; 18661138; 18230843; 20301758; 19813197; 20058079; 20833045; 20531024; 21917543; 22305237; 23218673 
GCDH	4189	2639	Glutaric aciduria, type I	AR	Pediatric		Biochemical; Cardiovascular; Neurologic	Biochemical		Early detection to allow treatment to decrease morbidity/mortality related to acute metabolic compensation, as well as dietary measures to  reduce lysine oxidation and influx (eg, with low lysine diet and arginine supplementation) and increase glutaryl-CoA detoxification (eg, with carnitine supplementation) can be beneficial	1137568; 624191; 3658174; 2027453; 1951469; 8139602; 8541831; 7564239; 8552212; 8900227; 11060535; 10699052; 12473778; 12888985; 15505396; 15954035; 15985591; 16641220; 17188916; 17203377; 17478444; 17622945; 17957492; 18775269; 19260933; 20084589; 20301313; 20732827; 21031586; 21912879; 22520952; 23225040; 23395213; 23884036
GCH1	4193	2643	Hyperphenylalaninemia, BH4-deficient, B; Autosomal Recessive Dopa-Responsive Dystonia with or without Hyperphenylalaninemia; GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia	AD/AR	Pediatric		Biochemical; Neurologic	Biochemical		In Hyperphenylalaninemia, BH4-deficient, B and Autosomal Recessive Dopa-Responsive Dystonia with or without Hyperphenylalaninemia, B, medical therapy (eg, BH-4, 5-HT, L-dopa) may be beneficial;  In GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia, which may not be easily clinically recognizable early, L-dopa can be effective	942621; 945938; 6734669; 3762960; 3822637; 3400489; 3041760; 2296384; 1899474; 8163996; 7874165; 7869202; 7730309; 9667588; 10208576; 10987649; 11113234; 11346370; 12084887; 12552057; 15753436; 16908750; 17111153; 20301681
GCK	4195	2645	Diabetes mellitus, permanent neonatal; Hyperinsulinemic hypoglycemia, familial 3	AD/AR	Pediatric		Endocrine	Endocrine		Recognition may allow prompt treatment of hypoglycemia; At initial diagnosis, hypoglycemia can be corrected with IV glucose in order to prevent brain damage; Long-term management includes diazoxide, somatostatin analogs, nifedipine, glucagon, recombinant IGF-I, glucocorticoids, human growth hormone, and dietary intervention; If aggressive medical management fails or is not possible (for example, in the case of some individuals with severe AR disease), pancreatic resection may be considered.	1360036; 1303265; 1570017; 8376578; 9435328; 9662401; 9469993; 11372010; 11916951; 14517946; 12941786; 15277402; 16965331; 17204055; 18399931; 18571549; 20301549; 20375417; 20301620 
GCLC	4311	2729	Gamma-glutamylcysteine synthetase deficiency	AR	Pediatric		Hematologic	Hematologic; Pharmacogenomic		Individuals have required exchange transfusion for infantile hyperbilirubinemia; Hemolysis-causing medications should be avoided; Supplementation (eg, with vitamins C or E) may be beneficial	5058793; 4852017; 2294991; 8634459; 10515893; 10733484; 12663448; 21657237 
GCM2	4198	9247	Hypoparathyroidism, familial isolated	AD/AR	Pediatric		Endocrine	Endocrine		Early recognition of electrolyte abnormalitities (eg, hypocalcemia) can allow prompt treatment in order to avoid severe sequelae	15863676; 18583467; 19940031; 20190276; 20463099; 22066718; 23155703
GCNT2	4204	2651	Blood group, Ii	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 	6858080; 3799539; 11739194; 12424189
GCSH	4208	2653	Glycine encephalopathy	AR	Pediatric		Biochemical; Neurologic; Ophthalmologic	Biochemical		There is no current effective treatment for severe disease; however, children with mutations associated with residual GCS enzyme activity treated aggressively early with sodium benzoate and N-methyl D-aspartate receptor site antagonists may have improved outcomes (no mutation-positive individuals with biallelic mutations have been described to date, but there is biochemical evidence of one such individuals)	6790577; 12402263; 20301531; 21470805
GDAP1	15968	54332	Charcot-Marie-Tooth disease, recessive intermediate, A; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis; Charcot-Marie-Tooth disease, axonal, type 2K; Charcot-Marie-Tooth disease, type 4A	AD/AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743579; 1174358012499475; 12707075; 12566285; 15805163; 17039978;  18492089; 20685671; 21753178; 22200116; 22971097 
GDF1	4214	2657	Transposition of the great arteries, dextro-looped 3; Double-outlet right ventricle	AD	N/A	N/A	Cardiovascular	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17924340
GDF2	4217	2658	Hereditary hemorrhagic telangiectasia, type 5	AD	Pediatric		Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Pulmonary	Cardiovascular; Gastrointestinal; Hematologic; Obstetric; Pharmacogenomic; Pulmonary		There are a number of surveillance/preventive/treatment based measures; These include: epistaxis treatment with humidification, lubricants, hormone therapy, anti-fibrinolytic agents, ablation, surgery, etc.; GI bleeding: iron replacement, hormonal or anti-fibrinolytic medication, surgery, etc.; Pulmonary AVM: catheter occlusion, and preventive measures such as antibiotic prophylaxis; symptomatic cerebral AVMs: surgery/embolotherapy, etc;  Severe hepatic AVMs: liver transplantation if medical management fails; Specific pregnancy-related screening may be indicated; Anemia: Iron replacement or transfusion; Avoidance of certain activities and use of anticoagulant and anti-inflammatory agents (including aspirin) in the case of significant bleeding; For PAH, medical therapy (eg, prostanoids, endothelin receptor antagonists, etc.) may be beneficial, but lung transplantation may be indicated	23972370
GDF3	4218	9573	Microphthalmia, isolated 7; Microphthalmia, isolated, with coloboma 6; Klippel-Feil syndrome 3, autosomal dominant; Coloboma, ocular	AD	N/A	N/A	Musculoskeletal; Ophthalmologic	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15241163; 19864492
GDF5	4220	8200	Acromesomelic dysplasia, Hunter-Thompson type; Fibular hypoplasia and complex brachydactyly; Multiple synostoses syndrome 2; Chondrodysplasia, Grebe type; Symphalangism, proximal 1B; Brachydactyly, type A1; Brachydactyly, type A1, C; Brachydactyly, type A2; Brachydactyly, type C	AD/AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13953230; 14159881; 4850715; 964999; 2624264; 2703235; 2363425; 8954778; 8589725; 9288098; 9489798; 12357473; 12121354; 12567410; 14735582; 16127465; 16222676; 16532400; 16014698; 16957682; 16892395; 17384641; 18629880; 18283415; 19956691; 20683927
GDF6	4221	392255	Microphthalmia, isolated 4; Microphthalmia, isolated, with coloboma 6; Coloboma, ocular; Klippel-Feil syndrome 1, autosomal dominant; Leber congenital amaurosis 17	AD/AR	N/A	N/A	Musculoskeletal; Ophthalmologic	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8533765; 17236135; 18425797; 19129173; 19864492; 21070663; 23307924
GDI1	4226	2664	Mental retardation, X-linked 41	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8826463; 9106537; 9668174; 9620768; 22002931
GDNF	4232	2668	Central hypoventilation syndrome	AD	Pediatric		Neurologic	Neurologic		Early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality	8896568; 8968758; 8896569; 9497256; 11973622; 11823451; 22729463 
GFAP	4235	2670	Alexander disease	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15409268; 13665382; 11138011; 11567214; 12034785; 12447932; 12034796; 14557587; 12975300; 15732097; 15732098; 16505300; 17894839; 17438228; 20301351; 21822933; 21917775; 21987397; 22118268; 22198646; 22488673; 22619055; 23254569; 23364391; 23634874
GFER	4236	2671	Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay 	AR	N/A	N/A	Audiologic/Otolaryngologic; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19409522
GFI1	4237	2672	Neutropenia, severe congenital, 2 autosomal dominant; Neutropenia, nonimmune chronic idiopathic, of adults 	AD	Pediatric		Allergy/Immunology/Infectious; Oncologic	Allergy/Immunology/Infectious; Oncologic	The condition can be clinically silent in some individuals	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; The condition may predispose to leukemia, and thus surveillance for hematologic anomalies may allow early diagnosis and treatment	1810106; 12778173; 12963840; 20560965 
GFM1	13780	85476	Combined oxidative phosphorylation deficiency 1	AR	N/A	N/A	Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15537906; 17160893; 21119709
GFPT1	4241	2673	Myasthenia,limb-girdle, with tubular aggregates	AR	Pediatric		Musculoskeletal; Neurologic	Musculoskeletal; Neurologic; Pharmacogenomic		Acetylcholinesterase inhibitors have been shown to result in a favorable treatment response; Avoidance of certain agents involved in neuromuscular transmission is indicated (eg, ciprofloxacin, chloroquine, lithium, phenytoin, beta-blockers, procainamide); Additional neurologic monitoring in pregnancy may be beneficial	8664562; 12467753; 21310273; 23108489
GGCX	4247	2677	Vitamin K-dependent clotting factors, combined deficiency of, 1; Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency	AD/AR/Digenic	Pediatric		Cardiovascular; Dermatologic; Hematologic; Musculoskeletal	Cardiovascular; Hematologic	Digenic inheritance (with ABCC6) has been reported in Pseudoxanthoma elasticum	In Vitamin K-dependent clotting factors, combined deficiency of, 1, vitamin K administration can be effective; In Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency, surveillance and prompt treatment of bleeding diatheses, as well as vascular malformations, may reduce morbidity and mortality	5936414; 426915; 7085873; 9845520; 17110937; 18800149; 19116367 
GH1	4261	2688	Isolated growth hormone deficiency, isolated, type IA; Isolated growth hormone deficiency, type 1B; Growth hormone deficiency, isolated, type II; Kowarski syndrome	AD/AR	Pediatric		Endocrine	Endocrine		Some individuals respond well to exogenous GH treatment, and benefits may be increased with early diagnosis and treatment; In certain forms, some individuals may manifest over time with a number of endocrine anomalies, and surveillance and early diagnosis and treatment can be beneficial	7714096; 8530604; 9076339; 9024229; 9024235; 8552145; 9276733; 9435425; 10678654; 11443201; 12915652; 12655557; 15713716; 16060904; 15671105; 17785701; 18554279; 17925337; 20852587 
GHR	4263	2690	Growth hormone insensitivity syndrome (Laron syndrome)	AD/AR	Pediatric		Endocrine	Endocrine		Medical treatment (eg, with recombinant human IGF1) can be beneficial	5707789; 4470894; 1349669; 8488849; 7565946; 8784089; 9140387; 9024266; 9360502; 9851797; 11297575; 11468686; 12679461; 15001620; 17148568; 18404972; 18073295; 19789204; 20583548; 19812236; 20606392; 20962506; 21325617; 21396571; 21900382; 22117696; 22423513; 22587301; 23006617
GHRHR	4266	2692	Isolated growth hormone deficiency, type 1B	AR	Pediatric		Endocrine	Endocrine		Combined treatment of GH and GNRHa can be effective in increasing final height, even in the case of advanced bone age and pubertal stage, though consideration related to cardiovascular-related treatment effects may be beneficial	8528260; 11443201; 17925337; 19733620; 21274317; 21044116; 22423511; 21816782; 21292919; 22416078 
GHSR	4267	2693	Short stature	AD/AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16511605; 19789204; 21646290 
GIF	4268	2694	Intrinsic factor deficiency	AR	Pediatric		Gastrointestinal; Hematologic	Gastrointestinal	Digenic disease (with FUT2 variants) has been described	Individuals typically present in infancy (though presentations at much later ages have been reported) with pernicious (megaloblastic) anemia, and vitamin B12 administration can be effective	2071148; 14695536; 14576042; 15738392; 20408840; 22929189; 23402911; 23430489
GIGYF2	11960	26058	Parkinson disease, autosomal dominant, 11	AD	N/A	N/A	Neurologic	General	The association with disease is controversial; Response to levodopa has been documented	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18358451; 18923002; 19250854; 19279319; 19449032; 19482505; 19845746;  19906271; 20004041; 20044296; 20060621; 20178831; 20641165; 20816920; 22115759
GIPC3	18183	126326	Deafness, autosomal recessive 15	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	9286457; 9106521; 17690910; 21326233; 21660509; 23226338; 23510777
GJA1	4274	2697	Oculodentodigital dysplasia, autosomal dominant	AD	Pediatric	Allelic with Hypoplastic left heart syndrome-1 (AD); Syndactyly, type III (AD); Oculodentodigital dysplasia, autosomal recessive (AR);  Atrioventricular septal defect 3 (AR)	Cardiovascular; Craniofacial; Dental; Musculoskeletal; Ophthalmologic	Cardiovascular	The conditions can involve multiple congenital anomalies	Individuals with cardiac arrhythmias have been reported, and surveillance (eg, with EKG) may allow early detection and treatment	2157843; 7815444; 11470490; 12457340; 15108203; 14974090; 14729836; 14981729; 15551259; 15637728; 16709485; 16816024; 17256797; 18412120; 19338053; 21670345; 22179534; 22214631 
GJA3	4277	2700	Cataract 14, multiple types	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10205266; 10746562; 15286166; 22312188; 22550389; 22876138; 23592915; 23734083
GJA5	4279	2702	Atrial fibrillation, familial 11; Progressive familial heart block, type I; Atrial standstill, digenic	AD/Digenic	Adult		Cardiovascular	Cardiovascular	Variants may be somatic or germline, and may contribute to phenotypes resulting from primary mutations in other genes (eg, SCN5A); Digenic inheritance (with SCN5A) has been described	Surveillance (eg, with echocardiography/electrocardiography) and medical/surgical intervention related to arrhythmias and associated sequelae may be beneficial	12522116; 16790700; 21076161; 22247482 
GJA8	4281	2703	Cataract 1, multiple types	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14059288; 9497259; 10480374; 11846744; 14627691; 16604058; 18006672; 19756179; 21720542; 20019893; 20597646; 20806042; 21921990 
GJB1	4283	2705	Charcot-Marie-Tooth neuropathy, X-linked dominant, 1 	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8266101; 10487913; 17100997; 17353473; 21254193; 21504505; 21692908; 21922480; 21692908; 22483671; 22577229 
GJB2	4284	2706	Deafness, autosomal recessive 1A; Deafness, digenic; Hystrix-like ichthyosis with deafness; Deafness, autosomal dominant 3A; Bart-Pumphrey syndrome; Keratoderma, palmoplantar, with deafness; Vohwinkel syndrome; Keratitis-icthyosis-deafness syndrome	AD/AR/Digenic	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dermatologic; Oncologic; Ophthalmologic	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Oncologic	In nonsyndromic deafness, onset of AD disease can be pre or postlingual; In syndromic disease,  although skin and other findings may be obvious in some individuals, the syndromic combination of features may not be as readily appreciated as being related to hearing impairment; Digenic inheritance (eg, with GJB3, GJB6) has been described	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In certain conditions (eg, KID syndrome), infectious and malignant complications may benefit from surveillance leading to microbial prophylaxis and early and aggressive treatment of infections and early detection and treatment of malignancy	6015974; 1532426; 8010352; 7748756; 9139825; 9529365; 9620796; 10218527; 10369869; 10633135; 10807696; 11298683; 11807148; 12047643; 11960582; 11912510; 11889383; 12372058; 12072059; 11918723; 12560944; 14694360; 15150777; 15482471; 14700667; 16222667; 16380907; 15994881; 15633193; 15691545; 15996214; 16840571; 17041943; 17330861; 993581; 17041943; 19050930; 18843290; 20815033; 20412116
GJB3	4285	2707	Deafness, autosomal recessive; Deafness autosomal dominant 2B; Deafness, autosomal dominant, with peripheral neuropathy; Deafness digenic 	AD/Digenic	Pediatric	Allelic with Erythrokeratodermia variabilis et progressiva (AD/AR); Deafness, autosomal dominant 2B (AD)	Audiologic/Otolaryngologic; Dermatologic; Neurologic	Audiologic/Otolaryngologic	Digenic inheritance (eg, with GJB2) has been described 	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	1828175; 9843209; 9843210; 10594760; 10798362; 11175305; 12019212; 12452892; 19050930
GJB4	4286	127534	Erythrokeratodermia variabilis et progressiva ; Erythrokeratodermia variabilis with erythema gyratum repens	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	148984; 11017804; 12648223; 19291775; 21564177; 22266302; 23037955 
GJB6	4288	10804	Deafness, autosomal recessive 1B; Deafness, digenic	AR/Digenic	Pediatric	The AD form can also cause deafness (Deafness, autosomal dominant 3B) (AD); Allelic with Ectodermal dysplasia, hidrotic (Clouston syndrome) (AD)	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dental; Dermatologic	Audiologic/Otolaryngologic	Digenic inheritance (eg, with GJB2) has been described	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	10471490; 11017065; 11807148; 11896458; 15150777; 15994881; 17041943; 18324688; 21465647
GJC2	17494	57165	Lymphedema, hereditary, IC; Spastic paraplegia 44, autosomal recessive; Leukodystrophy, hypomyelinating, 2	AD/AR	N/A	N/A	Cardiovascular; Dermatologic; Neurologic	General	Individuals with Lymphedema have been described with recurrent skin infections	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15192806; 16969684; 18094336; 19056803; 20513814; 20537300; 21266381; 21959080; 22610664; 22669416; 23143715; 24374284
GK	4289	2710	Glycerol kinase deficiency	XL	Pediatric		Biochemical; Neurologic	Biochemical		Specific dietary measures (eg, fat/glycerol-restricted diet) can be beneficial	6325658; 8651297; 9719371; 10736265; 11032329; 18607276; 21542762; 23009783
GLA	4296	2717	Fabry disease; Fabry disease, cardiac variant 	XL	Pediatric		Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Dermatologic; Neurologic; Ophthalmologic; Renal	Biochemical; Cardiovascular; Renal		In individuals with Fabry disease, enzyme therapy is available; Both males and females with mutations can suffer from significant multisystemic disease manifestations (including cardiovascular, cerebrovascular, and renal disease) and require monitoring and treatment, which can reduce morbidity; Individuals with Cardiac variant Fabry disease can have adult-onset left ventricular hypertrophy with or without renal failure, and early diagnosis and medical management may be beneficial	5411915; 4914726; 5466114; 6294821; 6283080; 3107860; 2539398; 2120125; 1645238; 1846223; 8395937; 7879606; 7817917; 7596372; 8807334; 8738659; 11105184; 10618424; 11694547; 11179018; 11732485; 11530143; 11386930; 11804208; 11889412; 12911529; 12519371; 15253767; 15162124; 15154115; 16298216; 16533976; 16926253; 16980809; 17371887; 17256799; 17362993; 17224688; 18023222; 19473999; 19318041; 19843486; 19853240; 19959221; 19965549; 19745746; 20301469; 21502868; 22431073; 22450713; 22498845; 22704481; 22731890; 22878429; 22880956; 22881192; 22880956; 22898981; 22963910; 22998007; 23040658; 23089251; 23094092
GLB1	4298	2720	Mucopolysaccharidosis type IVB (Morquio syndrome B);  GM1-gangliosidosis, type I; GM1-gangliosidosis, type II; GM1-gangliosidosis, type III	AR	N/A	N/A	Biochemical; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14209687; 14261015; 4227214; 4173446; 4231206; 4243740; 5541675; 4650864; 5031983; 4143049; 4420522; 4139552; 131309; 62026; 404231; 416929; 99363; 121869; 6777095; 6791574; 6791575; 7173264; 3926630;  3917501; 1909089; 1928092; 1907800; 1336295; 1353343; 8198123; 7586649; 10841810; 10737981; 11511921; 12644936; 15986423; 16466959; 16941474; 17309651; 18524657; 19472408; 20175788; 21204790; 21497194; 22234367; 23046582 
GLDC	4313	2731	Glycine encephalopathy	AR	Pediatric		Biochemical; Neurologic; Ophthalmologic	Biochemical		Treatment may be less effective for individuals with severe disease; however, aggressive early treatment with sodium benzoate and N-methyl D-aspartate receptor site antagonists in individuals with mutations associated with residual GCS enzyme activity have been reported to result in improved outcomes	10873393; 12402263; 15077252; 15236413; 15851735; 16151895; 16404748; 16450403; 17361008; 20301531; 20933183; 21411353; 23349517
GLE1	4315	2733	Arthrogryposis, lethal, with anterior horn cell disease; Lethal congenital contracture syndrome 1 	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7966188; 7897624; 18204449
GLI2	4318	2736	Culler-Jones syndrome	AD	Pediatric	Allelic with Holoprosencephaly 9 (AD)	Craniofacial; Endocrine; Musculoskeletal; Neurologic 	Endocrine		While initially reported (and named) as associated with holoprosencephaly the more classic presentation is (sometimes subclinical) endocrinological manifestations, including treatable deficiency, such as of thyroid hormone and growth hormone, along with postaxial polydactyly	14581620; 15994174; 17096318; 20685856; 22967285; 23112757; 23304807; 23408573; 24744436
GLI3	4319	2737	Acrocallosal syndrome; Pallister-Hall syndrome; Grieg cephalopolysndactyly syndrome; Postaxial polydactyly type A1; Polydactyly, preaxial, type IV; Polydactyly, postaxial, types A1 and B	AD	N/A	N/A	Craniofacial; Endocrine; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4317883; 7211952; 6295159; 6641002; 2596511; 1650914; 9054938; 9042919; 9302279; 10441570; 10945658; 10678662; 12794692; 14608643; 15811011; 15739154; 18000979; 18435847; 20301619; 20301638; 20503312; 20583172; 20672375; 21108399; 21320477; 21326280; 22428873; 23633388
GLIS2	29450	84662	Nephronophthisis 7	AR	N/A	N/A	Renal	General	Renal transplantation has been desribed	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17618285
GLIS3	28510	169792	Diabetes mellitus, neonatal, with congenital hypothyroidism	AR	Pediatric		Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Endocrine		Prompt treatment (eg, of ketoacidosis and dehydration) can avoid morbidity; Treatment of congenital hypothyroidism can improve outcome	12966531; 16715098
GLMN	14373	11146	Glomuvenous malformations	AD	N/A	N/A	Cardiovascular; Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11845407; 23375657
GLRA1	4326	2741	Hyperekplexia, hereditary	AD/AR	Pediatric		Neurologic	Neurologic		Neonates are at risk of sudden death from apnea/aspiration, and surveillance, as well as primary prevention with medical treatments (eg, clonazepam) may be beneficial	1334371; 8298642; 7881416; 11104232; 8571969; 16832093; 20301437
GLRB	4329	2743	Hyperekplexia 2	AR	Pediatric		Neurologic	Neurologic		Neonates are at risk of sudden death from apnea/aspiration, and surveillance, as well as primary prevention with medical treatments (eg, clonazepam) may be beneficial	11929858; 21391991; 20301437
GLRX5	20134	51218	Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive	AR	Pediatric		Hematologic	Hematologic		An individual has been reported who required RBC transfusions, and in whom iron chelation was partially effective	17485548
GLUD1	4335	2746	Hyperinsulinemic hypoglycemia, familial; Hyperammonemia-hyperinsulinism	AD/AR	Pediatric		Biochemical; Endocrine	Biochemical; Endocrine		At initial diagnosis, hypoglycemia can be corrected with IV glucose in order to prevent brain damage; Long-term management includes diazoxide, somatostatin analogs, nifedipine, glucagon, recombinant IGF-I, glucocorticoids, human growth hormone, and dietary intervention (including with leucine restrictions in some recessive forms of disease); If aggressive medical management fails or is not possible, pancreatic resection may be considered	9843361; 9571255; 9469993; 10636977; 10871207; 11518822; 11241047; 11297618; 11214910; 19046187; 20857847; 20301549; 22106762; 21932603; 22759688 
GLUL	4341	2752	Glutamine deficiency, congenital	AR	Pediatric		Biochemical; Neurologic	Biochemical		Supplementation with glutamine has been reported as resulting in clinical (measured by alertness) and electroencephalogram-documented improvements	16267323; 21353613; 22830360 
GLYCTK	24247	132158	D-glyceric aciduria	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4599249; 2537226; 20949620
GM2A	4367	2760	GM2-gangliosidosis, AB variant	AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5135907; 10364519; 11339652 
GMPPA	22923	29926	Alacrima, achalasia, and mental retardation syndrome	AR	N/A	N/A	Audiologic/Otolaryngologic; Dermatologic; Gastrointestinal; Neurologic; Ophthalmologic	General	Onset and severity of hearing impairment is unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24035193
GMPPB	22932	29925	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14; Limb-girdle muscular dystrophy-dystroglycanopathy, type B, 14; Limb-girdle muscular dystrophy-dystroglycanopathy, type C, 14	AR	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	Cardiovascular		Cardiovascular complications, including long QT syndrome and cardiomyopathy, have been described, and awareness may allow surveillance and prompt management	23768512
GNA11	4379	2767	Hypocalcemia 2, autosomal dominant; Hypocalciuric hypercalcemia, autosomal dominant	AD	Pediatric		Endocrine	Endocrine		In Hypoparathyroidism (Hypocalcemia), early recognition of electrolyte abnormalitities (eg, hypocalcemia) can allow prompt appropriate management in order to avoid and/or promptly treat severe sequelae, which can include hypocalcemic seizures; In Hypocalciuric hypercalcemia, accurate diagnosis may be important in order to decrease the use of unhelpful therapies	6278146; 23782177; 23802516; 23802536; 24823460
GNAI3	4387	2773	Auriculocondylar syndrome 1	AD	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22560091; 23315542
GNAL	4388	2774	Primary torsion dystonia	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23222958
GNAS	4392	2778	Pseudohypoparathyroidism, type IA; Pseudohypoparathyroidism, type IB; Pseudohypoparathyroidism, type IC; Progressive osseous heteroplasia; McCune-Albright syndrome	AD	Pediatric		Dermatologic; Endocrine; Musculoskeletal; Oncologic; Renal	Endocrine; Oncologic; Renal	Mosaic mutations have been described; PPHP occurs with paternal inheritance	In Pseudohypoparathyroidism, medical treatment (eg, with calcium and vitamin D therapy) of electrolyte abnormalities and related complications such as osteitis fibrosa cystica can be effective, and complications; Surveillance and early treatment of endocrinological manifestations (eg, hypothyroidism, hypogonadism) can be beneficial; In McCune-Albright syndrome, medical (eg, related to estrogen production, hyperthyroidism, growth hormone production) and surgical (eg, to treat adrenal pathology, hyperthyroidism) treatment of endocrinopathies may be beneficial, and surveillance and early and specific treatment for manifestations such as a number of types of neoplasms, including GH-producing tumors (eg, with long-acting octreotide, GHR antagonists) can be beneficial, as well as surveillance for and treatment of Cushing syndrome (some patients require adrenalectomy)	13005676; 5906056; 1083395; 198661; 219790; 431133; 6265935; 3126297;  2829196; 2273209; 2109828; 3093862; 2122458; 1955519; 1944469; 1400888; 1621772; 1424186; 1594625; 1346061; 8421479; 7980957; 8126048; 8126161; 7739708; 7671486; 9226216; 9506752; 0614538; 10356155; 10190480; 11073544; 10646121; 11067869; 11095461; 10998448; 11600516; 11406605; 11297617; 11583302; 11397863; 11029463; 12414879; 12024004; 12407707; 11788646; 11784876; 14561710; 12605446; 12727968; 12858292; 14557424; 12624854; 15001590; 15126527; 15711092; 16060910; 15537666; 16984995; 17405850; 17651445; 18553568; 18416659; 18397987; 20480732; 19858129; 21816789; 21488135; 21357941; 22640971 
GNAT1	4393	2779	Night blindness, congenital stationary, autosomal dominant 3; Night blindness, congenital stationary, autosomal recessive	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8673138; 22190596
GNAT2	4394	2780	Achromatopsia 4	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12205108; 12077706; 15557429; 21107338 
GNB4	20731	59345	Charcot-Marie-Tooth disease, dominant intermediate F	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20627571; 23434117
GNE	23657	10020	Sialuria, French type ; Nonaka myopathy; Inclusion body myopathy, autosomal recessive	AD/AR	N/A	N/A	Biochemical; Gastrointestinal; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7252518; 2443758; 2808337; 1779656; 8439453; 10330343; 11528398; 11486897; 11326336; 12473780; 11916006;  12473753; 12177386; 12473769; 16372135; 17718674; 20059379; 20175955; 20300792; 20301343; 20301439; 20346669; 21131200; 21708040; 22196754; 22507750; 22883483; 23127962; 24796702
GNMT	4415	27232	Glycine N-methyltransferase deficiency	AR	N/A	N/A	Biochemical; Gastrointestinal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11596649; 11810299
GNPAT	4416	8443	Rhizomelic chondrodysplasia punctata, rhizomelic, type 2	AR	N/A	N/A	Biochemical; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1405476; 8466247; 7530787; 7541833; 9536089; 20583171; 21990100 
GNPTAB	29670	79158	Mucolipidosis III alpha/beta (Pseudo-Hurler polydstrophy); Mucolipidosis II alpha/beta (I-cell disease)	AR	N/A	N/A	Biochemical; Cardiovascular; Musculoskeletal; Neurologic	General	Bisphosphonate therapy may be beneficial for bone pain; The conditions may include severe cardiac manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4958870; 4247489; 4327936; 6461005; 6309902; 3003148; 3001079; 7628121; 12705498; 16116615; 15633164; 16094673; 16630736; 19197337; 19659762; 20301728; 21416587; 22162509;  22495880 
GNPTG	23026	84572	Mucolipidosis III gamma	AR	N/A	N/A	Biochemical; Cardiovascular; Musculoskeletal	General	The condition may include severe cardiac manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10712439; 15532026; 19370764; 19659762; 20034096; 20951619; 21792934 
GNRH1	4419	2796	Hypogonadotropic hypogonadism 12 with or without anosmia	AR/Digenic	Pediatric		Endocrine; Genitourinary; Neurologic	Endocrine	Digenic inheritance (with NR0B1) has been reported;	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	19535795; 19567835; 20301509; 20389089; 20887715; 21722705 
GNRHR	4421	2798	Hypogonadotropic hypogonadism; Fertile eunuch syndrome	AD/AR/Digenic	Pediatric		Endocrine; Genitourinary	Endocrine	Digenic inheritance (with FGFR1) has been reported	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	13061573; 9371856; 10690855; 11397842; 17235395; 20301455; 20301509; 22035731; 22724017
GNS	4422	2799	Mucopolysaccharidosis IIID (Sanfilippo syndrome D)	AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6450420; 12624138; 12573255; 17998446; 19650410; 20232353 
GORAB	25676	92344	Geroderma osteodysplasticum	AR	N/A	N/A	Dermatologic; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	631850; 474638; 3236370; 8213917; 8723088; 9018419; 18997784; 18348262; 19681135; 21204221
GOSR2	4431	9570	Epilepsy, progessive myoclonic 6	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21549339; 23449775
GP1BA	4439	2811	Bernard-Soulier syndrome, type A2; Bernard-Soulier syndrome, type A1; Pseudo-von Willebrand disease	AD/AR	Pediatric		Hematologic	Hematologic; Pharmacogenomic		Preventive measures (eg, in the case of surgery) and treatment of bleeding episodes can be beneficial; Specific medications (eg, certain anesthetics) that interfere with platelet function should be avoided	18116504; 14081293; 6019024; 6286015; 6798442; 6333901; 2308962; 2052556; 1901273; 1730088; 8384898; 9616133; 11222377; 14711733; 21173099; 22102188; 23014764 
GP1BB	4440	2812	Bernard-Soulier syndrome; Giant platelet disorder, isolated	AR	Pediatric		Hematologic	Hematologic; Pharmacogenomic		Preventive measures (eg, in the case of surgery) and treatment of bleeding episodes can be beneficial; Specific medications (eg, certain anesthetics) that interfere with platelet function should be avoided	18116504; 14081293; 6019024; 1901273; 8703016; 9116284; 9616133; 21173099; 21800012; 22102188 
GP6	14388	51206	Bleeding disorder, platelet-type, 11	AR	Pediatric		Hematologic	Hematologic		Individuals may demonstrate a bleeding diathesis (including postraumatic/postsurgical), and surveillance and prompt treatment of bleeding episodes may reduce morbidity	19549989; 19552682
GP9	4444	2815	Bernard-Soulier syndrome	AR	Pediatric		Hematologic	Hematologic		Preventive measures (eg, in the case of surgery) and treatment of bleeding episodes can be beneficial; Specific medications (eg, certain anesthetics) that interfere with platelet function should be avoided	18116504; 14081293; 6019024; 1901273; 8481514; 9616133; 16268478; 17109744; 21173099; 21699652 
GPC3	4451	2719	Simpson-Golabi-Behmel syndrome, type 1	XL	Pediatric		Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Cardiovascular; Oncologic	The condition may involve multiple congenital anomalies	The disorder, which can include certain types of tumors, should be clinically recognizable, but surveillance for neoplasms may allow early diagnosis and treatment, which may ameliorate morbidity and mortality; Awareness of the risk of cardiac sequelae, which can include anatomic anomalies and dysrhythmias, may allow prompt detection and management	1227524; 6490008; 6538755; 3177455; 1479609; 7909248; 8589713; 9950367; 10232747; 11477610; 16158429; 17850639; 17603795; 18203194; 2018065; 20301398; 20950395; 21434539; 21362501; 22807161; 23463737; 23606591
GPC6	4454	10082	Omodysplasia 1	AR	N/A	N/A	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19481194
GPD1	4455	2819	Hypertriglyceridemia, transient infantile	AR	Pediatric		Gastrointestinal	Gastrointestinal		Individuals may present with failure to thrive and other sequelae of disease, and dietary management (with high-calorie, low-fat diet) has been described as beneficial	22226083; 24549054
GPD1L	28956	23171	Brugada syndrome 2	AD	Pediatric		Cardiovascular	Cardiovascular; Pharmacogenomic		Surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial;  Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever	11839626; 17967977; 17967976
GPHN	15465	10243	Hyperekplexia, autosomal dominant; Molybdenum cofactor deficiency, type C	AD/AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	General	In Hyperekplexia, autosomal dominant, evidence for pathogenicity is unclear (though multiple medical treatments, including clonazepam may be beneficial)	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11095995; 12684523; 20301437; 21031595; 22040219 
GPI	4458	2821	Hemolytic anemia, nonspherocytic due to glucose phosphate isomerase deficiency	AD	Pediatric		Hematologic	Hematologic; Pharmacogenomic		Anemia may be ameliorated by splenectomy, and it may be beneficial to avoid agents (or provide monitoring if such agents are unavoidable) that may precipitate hemolytic anemia	5672849; 469896; 3796702; 10916680; 17041899; 20516363; 22782259 
GPIHBP1	24945	338328	Hyperlipoproteinemia, type ID	AR	Pediatric		Cardiovascular; Gastrointestinal	Cardiovascular; Gastrointestinal		Individuals have been described with severe chylomicronemia/hypertriglyceridemia, and dietary measures (eg, low fat diet) have been described as beneficial related to sequelae such as pancreatitis and colitis, as well as other cardiovascular manifestations	17883852; 19304573; 20026666; 20124439; 21816778; 22239554; 24614124
GPR143	20145	4935	Nystagmus 6, congenital, X-linked; Ocular albinism, type I	XL	N/A	N/A	Dermatologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7915878;  7647783; 8634705; 9887374; 9529334; 11214907; 11520764; 11793467; 17516023; 18523664; 19123159; 19390656; 19604113; 19610097; 20301517; 20649618; 21274678; 21348135; 21423867; 22916221 
GPR179	31371	440435	Night blindness, congenital stationary, type 1E	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22325361; 22325362; 23714322
GPR56	4512	9289	Polymicrogyria, bilateral frontoparietal; Polymicrogyris, bilateral perisylvian	AR	N/A	N/A	Neurologic	General	Mutations involving cis-regulatory elements have additionally been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15044805; 20929962; 21349848; 21723461;  23274687; 24531968
GPR98	17416	84059	Usher syndrome, type IIC	AR/Digenic	Pediatric		Audiologic/Otolaryngologic; Ophthalmologic	Audiologic/Otolaryngologic	Digenic inheritance has been described (withPDZD7)	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	12402266; 14740321;19357116; 18854872; 0440071; 21174530
GPSM2	29501	29899	Chudley-McCullough syndrome; Deafness, autosomal recessive 82	AR	Pediatric		Audiologic/Otolaryngologic; Neurologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	20602914; 20602914 
GPX4	4556	2879	Sedaghatian-type spondylometaphyseal dysplasia	AR	N/A	N/A	Cardiovascular; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22529034; 24706940
GRHL2	2799	79977	Ectodermal dysplasia/short stature syndrome	AD/AR	Pediatric	Allelic with Deafness, autosomal dominant 28 (AD)	Audiologic/Otolaryngologic; Dental; Dermatologic; Musculoskeletal	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	12393799; 25152456
GRHL3	25839	57822	van der Woude syndrome 2	AD	N/A	N/A	Craniofacial; Dental; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24360809
GRHPR	4570	9380	Hyperoxaluria, primary, type II	AR	Pediatric		Biochemical; Renal	Renal		Fluid intake and medical management (eg, orthophosphate, potassium citrate, magnesium) to prevent calcium oxalate crystallization can be effective; Temporary dialysis for ESRD, followed by transplantation may be required; Surveillance of renal function and related parameters may be effective; Dehydration and excessive intake of oxalate-rich foods should be avoided	4321474; 2040928; 7987654; 9243228; 10484776; 11030416; 11518794; 11156702; 11135054; 11477177; 12185464; 14635115; 12897114; 15327387; 16756993; 17510093; 19296982; 20301742; 24116921
GRIA3	4573	2892	Mental retardation, X-linked 94	XL	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17568425; 17989220; 19449417; 22124977 
GRIK2	4580	2898	Mental retardation, autosomal recessive 6	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17120046; 17847003
GRIK4	4582	2900	Response to antidepressant treatment with citalopram	AD	Pediatric		General	Pharmacogenomic		The choice of medications may be affected by the presence of variants	17671280; 18370842; 19924111 
GRIN1	4584	2902	Mental retardation, autosomal dominant 8	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21376300
GRIN2A	4585	2903	Epilepsy with neurodevelopmental defects	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20890276; 24504326
GRIN2B	4586	2904	Mental retardation, autosomal dominant 6; Epileptic encephalopathy, early infantile 27	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20890276; 22521361; 22495309; 23934111; 24272827
GRIP1	18708	23426	Fraser syndrome	AR	N/A	N/A	Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22510445
GRK1	10013	6011	Oguchi disease 2	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14281981; 9020843; 17070587; 17765441; 19753316; 22959359
GRM1	4593	2911	Spinocerebellar ataxia, autosomal recessive 13	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22901947
GRM6	4598	2916	Night blindness, congenital stationary, type 1B	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11874764; 15781871; 16249515; 16622103; 22008250 
GRN	4601	2896	Frontotemporal lobar degeneration with TDP43 inclusions, GRN-related; Neuronal ceroid lipofuscinosis 11	AD/AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6497355; 9633693; 16862116; 16862115; 16983677; 16401619; 16983685; 16495329; 17436289; 17210807; 18392865; 18543312; 18183624; 18413474; 18703462; 18723524; 19884572; 20142524; 20142525; 22338605; 22366770; 22491866; 22608501; 22647257; 22815225; 22890101; 22906081; 22986778 
GRXCR1	31673	389207	Deafness, autosomal recessive 25	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	20137778
GRXCR2	33862	643226	Deafness, autosomal recessive 101	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	24619944
GSC	4612	145258	Short Stature, Auditory-Canal Atresia, Mandibular Hypoplasia, and Skeletal Abnormalities (SAMS)	AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Genitourinary; Musculoskeletal	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	9475592; 24290375
GSN	4620	2934	Amyloidosis, Finnish type	AD	Adult		Cardiovascular; Dermatologic; Neurologic; Ophthalmologic; Renal	Cardiovascular	Recessive disease has been reported as resulting in a more severe phenotype 	Individuals with cardiac conduction disease have been described, and surveillance (eg, with electocardiogram) may allow early management (eg, with pacemaker)	4543600; 2153578; 2176164; 1322359; 1311149; 1315718; 8395367; 8684801; 11754099; 16258946; 22068858; 22622774 
GSS	4624	2937	Glutathione synthetase deficiency	AR	Pediatric		Biochemical; Hematologic; Neurologic; Ophthalmologic	Biochemical;Hematologic; Pharmacogenomic		Medical therapy (eg, N-acetylcysteine, vitamin E), may improve outcomes, especially if administered early; Hemolysis-causing drugs should be avoided; Acidosis can be medically corrected	13731008; 5901982; 5486400; 5476481; 481537; 3944259; 2502672; 1770788; 1986110; 7937585; 8896573; 11445798; 15717202; 15990954; 16435214; 17206463; 17479648; 19728142; 21988557 
GTF2H5	21157	404672	Trichothiodystrophy	AR	N/A	N/A	Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2189905; 8783572; 15220921; 18470933; 18603627
GUCA1A	4678	2978	Cone dystrophy 3/Cone-rod dystrophy 14	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9425234; 15735604; 15953638; 15790869; 19459154 
GUCA1B	4679	2979	Retinitis pigmentosa 48	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15452722
GUCY1A3	4685	2982	Moyamoya disease 6 with achalasia	AR	Pediatric		Cardiovascular; Gastrointestinal	Cardiovascular		Surveillance for cardiovascular complications, as well as related preventive measures to help control contributory factors and clinical manifestations (eg, hypertension) may reduce morbidity and mortality	24581742
GUCY2C	4688	2984	Diarrhea 6; Meconium ileus	AD/AR	Pediatric		Gastrointestinal; Renal	Gastrointestinal; Renal	Individuals with Meconium ileus have been described with features of Diarrhea 6 (in terms of chronic diarrhea in infancy)	In Diarrhea 6,  individuals may present in infancy with relatively severe dehydration, metabolic acidosis, and electrolyte disturbances, and preventive measures and early treatment may be beneficial; Awareness of sequelae that may require surgical interventions (eg, small bowel obstruction) may allow prompt recognition and treatment; Individuals may be at increased risk of urolithiasis, and preventive measures and prompt treatment may be beneficial; In Meconium ileus, individuals may present in infancy with relatively severe dehydration, metabolic acidosis, and electrolyte disturbances, and preventive measures and early treatment may be beneficial	4006357; 22436048; 22436048; 22521417
GUCY2D	4689	3000	Cone-rod dystrophy 6; Leber congenital amaurosis, type 1; Cone-Rod dystrophy, autosomal recessive	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8554074; 9097965; 9618177; 11709018; 12015276; 12325031; 12623820; 12552567; 15024725; 20006823; 20301475; 20517349; 22194653; 22695961 
GUSB	4696	2990	Mucopolysaccharidosis type VII	AR	N/A	N/A	Biochemical; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic	General	The condition can include cardiac manifestations; Bone marrow transplant has been described as benefitting some clinical parameters	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4265197; 144057; 101485; 6813001; 1702266; 7680524; 9099834; 9543069; 12403825; 12522561; 12748853; 19224584 
GYG1	4699	2992	Glycogen storage disease XV	AR	Pediatric		Biochemical; Cardiovascular	Cardiovascular		Surveillance to allow early diagnosis and treatment of cardiac complications (eg, treatment of heart failure and arrhythmias via medical management and ICD placement) may be beneficial	20357282
GYPA	4702	2993	Blood group, MN locus; Blood group, Erik	BG	Pediatric	 	Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	275842; 7040988; 7052193; 8245024
GYPB	4703	2994	Blood group, Ss	BG	Pediatric	 	Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	3818169; 3456608; 2823938; 3477806
GYPC	4704	2995	Blood group, Gerbich; Blood group, Webb; Blood group, Duch	BG	Pediatric	 	Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	5011657; 7095818; 3539763; 1991173; 1719701; 1413665; 8157284; 11719395; 12469115
GYS1	4706	2997	Glycogen storage disease, type 0, muscle	AR	Pediatric		Biochemical; Cardiovascular; Musculoskeletal; Neurologic	Cardiovascular	An individual with seizures has been described, but it is not clear if this finding was primarily related to the underlying condition	Individuals may manifest with findings such as hypertrophic cardiomyopathy and sudden cardiac arrest and death, and treatment with cardioprotective medications (eg, beta-blockers) has been reported as beneficial	17928598; 21958591 
GYS2	4707	2998	Glycogen storage disease, type 0, liver	AR	Pediatric		Biochemical; Gastrointestinal; Neurologic	Biochemical		Dietary management (eg, with frequent and overnight feeds) can be beneficial	21032403; 4505568; 8831078; 9691087; 11483824; 12794686; 18341095; 20051115; 23426827
H19	4713	283120	Wilms tumor 2; Beckwith-Wiedemann syndrome	AD (with imprinting)	Pediatric		Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Renal	Endocrine; Oncologic	Inheritance involves imprinting; The condition may include the presence of multiple congenital anomalies	Surveillance for and early diagnosis of Wilms tumor could  be beneficial in order to allow early treatment, which could benefit related morbidity and mortality; Recognition and surveillance for and treatment of neonatal hypoglycemia can be beneficial	15314640; 15743916; 18836444
H6PD	4795	9563	Cortisone reductase deficiency	AR 	N/A	N/A	Endocrine	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10522997; 12858176; 15827106; 18628520
HADH	4799	3033	3-hydroxyacyl-CoA dehydrogenase deficiency	AR	Pediatric		Biochemical; Endocrine; Gastrointestinal	Cardiovascular; Endocrine; Gastrointestinal		Individuals may present with hypoglycemic seizures, which can lead to neurologic sequelae, and measures to treat/prevent hypoglycemia (eg, with diazoxide) can be effective; In the longer-term, medical and/or surgical treatment (eg, with pancreatectomy, glucagon) may help prevent severe sequelae; Surveillance for cardiovascular manifestations (eg, cardiomyopathy) may allow prompt management; Liver transplant has been described	4193973; 904979; 1835339; 10347277; 10931422; 11489939; 12400064; 14693719; 15870679; 16725361; 19417036; 19318379; 20301549; 21347589; 23273570 
HADHA	4801	3030	Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency; Trifunctional protein deficiency	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic	Biochemical	Variants are also related to maternal HELLP syndrome and Acute fatty liver of pregnancy	Early diagnosis to allow interventions such as avoidance of fasting and urgent metabolic care in the setting of acute metabolic decompensation can reduce morbidity and mortality	7813533; 7811722; 7846063; 8770876; 10518281; 12621125; 17143551; 21549624; 21103935; 21630065 
HADHB	4803	3032	Trifunctional protein deficiency	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic	Biochemical	Variants are also related to maternal HELLP syndrome and Acute fatty liver of pregnancy	Early diagnosis to allow interventions such as avoidance of fasting and urgent metabolic care in the setting of acute metabolic decompensation may reduce morbidity and mortality	8163672; 7738175; 8651282; 9259266; 12754706; 19699128; 21549624; 22000755; 21630065 
HAL	4806	3034	Histidinemia	AR	N/A	N/A	Biochemical	General	The clinical relevance of the condition is unclear 	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13704885; 13863215; 4421298; 6192285; 6410118; 8669938; 15806399; 20156889 
HAMP	15598	57817	Hemochromatosis, type 2B	AR	Pediatric		Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic	Biochemical; Gastrointestinal; Hematologic	Digenic inheritance (with HFE) has been reported; HAMP variants may contribute to severity/manifestations of hemochromatosis associated with mutations in other genes	Patients may benefit from surveillance related to iron overload, and from interventions such as venesection; Certain agents should be avoided (eg, alcohol consumption; iron-containing compounds; uncooked seafood); Hormone therapy may be beneficial in order to prevent osteoporosis	10205270; 12490283; 12915468; 12469120; 15099344; 15345104; 14670915; 15024747; 15198949; 16204153; 19214511; 20301349; 22297252; 22924847 
HARS	4816	3035	Usher syndrome, type 3B	AR	Pediatric		Audiologic/Otolaryngologic; Neurologic; Ophthalmologic	Audiologic/Otolaryngologic	Hearing loss data unclear but suggestive of early loss	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	22279524
HARS2	4817	23438	Perrault syndrome 2	AR	Pediatric		Audiologic/Otolaryngologic; Endocrine; Genitourinary; Obstetric	Audiologic/Otolaryngologic	 Females have been described as being affected by genitourinary anomalies in addition to hearing impairment	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	517579; 21464306
HAX1	16915	10456	Neutropenia, severe congenital, 3	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Neurologic; Oncologic	Allergy/Immunology/Infectious; Oncologic		Individuals manifest with findings including susceptibility to severe bacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Use of G-CSF has been reported, as well as treatment with BMT; Surveillance for malignancies may allow early detection and treatment, as there is an increased risk of manifestations such as acute myeloid leukemia and myelodysplastic syndrome	13326376; 17187068; 18337561; 21108402
HBA1	4823	3039	Alpha-thalassemia (Hemoglobin Bart syndrome); Alpha-thalassemia (Hemoglobin H  disease)	AR/Digenic	Pediatric		Hematologic	Hematologic; Pharmacogenomic		RBC transfusions may be effective for individuals with HbH disease during hemolytic/aplastic crises;  Individuals with HbH disease should be monitored for hemolytic/aplastic crisis during febrile episodes; Monitoring should be performed in order to assess iron overload; Individuals with HbH should avoid inappropriate iron therapy, oxidant drugs (eg sulphonamides), some antimalarials; Mutations may also result in a variety of hematologic disease (eg, hemolytic anemia), and genetic diagnosis may aid early recognition and treatment, as well as avoid uneccesary treatments (eg, splenectomy in Heinz body anemia)	980019; 6199634; 2649166; 2831458; 4138824; 7615401; 9405682; 9516118; 10215545; 10339580; 11283697; 12393486; 16138310; 19205971; 20301608; 21381239; 22531344; 22631041; 24006930; 24081251; 24136020
HBA2	4824	3040	Alpha-thalassemia (Hemoglobin Bart syndrome); Alpha-thalassemia (Hemoglobin H  disease)	AR/Digenic	Pediatric		Hematologic	Hematologic; Pharmacogenomic		RBC transfusions may be effective for individuals with alpha-thalassemia or HbH disease during hemolytic/aplastic crises; Individuals with HbH disease should be monitored for hemolytic/aplastic crisis during febrile episodes; Monitoring should be performed in order to assess iron overload; Individuals with HbH should avoid inappropriate iron therapy, oxidant drugs (eg sulphonamides), some antimalarials; Mutations may also result in a variety of hematologic disease (eg, hemolytic anemia), and genetic diagnosis may aid early recognition and treatment, as well as avoid uneccesary treatments (eg, splenectomy in Heinz body anemia)	9516118; 2831458; 4138824; 15266345; 12393486; 16461765; 20301608; 22631041 
HBB	4827	3043	Beta-thalassemia; Sickle cell disease; Thalassemia-beta, dominant inclusion body; Other Thalassemias/Hemoglobinopathies	AD/AR/Digenic	Pediatric	Allelic with Hereditary persistence of fetal hemogoblin (AD)	Allergy/Immunology/Infectious; Cardiovascular; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Pulmonary	Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Pulmonary	The LCRB region is also relevant	For beta-thalassemia, specific treatments (eg, transfusions, as well as managing related issues such as potential iron overload), can be effective; For sickle cell anemia, surveillance, immune prophylaxis, and preventive measures (eg, hydroxyurea, prophylactic antibiotics) can be effective in reducing morbidity, as well as aid in the prompt recognition and treatment of crises and sequelae; Mutations may also result in a variety of hematologic disease (eg, hemolytic anemia), and genetic diagnosis may aid early recognition and treatment (eg, with RBC transfusion), as well as avoid uneccesary treatments (eg, splenectomy in Heinz body anemia)	4232783; 4351905; 49057; 7137165;  3048433; 2563949; 1971109; 1707292; 1586746; 8201467; 7715639; 8982148; 10861320; 12614204; 19036119; 19486366; 20098328; 20301599; 20305663; 21131035; 20301551; 22622672; 22631042; 22645178; 22740566; 22786487; 22857974; 22892550; 22899478; 22923496; 22972063; 23076916; 23108767 
HBG1	4831	3047	Hereditary persistence of fetal hemoglobin	AD	N/A	Allelic with Hereditary persistence of fetal hemogoblin (AD)	Hematologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2578620; 2423160; 21057501 
HBG2	4832	3048	Cyanosis, transient neonatal	AD	Pediatric	Allelic with Hereditary persistence of fetal hemoglobin (AD)	Hematologic	Hematologic		Though a range of severity has been described, some individuals have been reported as requiring supplemental oxygen and/or RBC transfusions	6158500; 6174163; 6205403; 6208955; 2483933; 8811323; 12603090; 21561349; 22935660 
HCCS	4837	3052	Microphthalmia, syndromic 7 (MIDAS syndrome)	XL	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	Audiologic/Otolaryngologic; Cardiovascular		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; As individuals have been described with a variety of cardiovascular anomalies, surveillance (eg, with echocardiogram/electrocardiogram) may allow detection and early management of related manifestations	16059943; 17033964; 17893649; 20301767; 21200317
HCFC1	4839	3054	Combined methylmalonic acidemia and hyperhomocysteinemia	XL	Pediatric		Biochemical; Neurologic	Biochemical		Medical interventions (eg, cofactor therapy with injectable hydroxycobalamin) and dietary management (eg, high-calorie, low protein diet and avoidance of fasting, with measures taken to avoid/treat decompensation) may be to beneficial in both acute and chronic states	24011988
HCN1	4845	348980	Epileptic encephalopathy, early infantile, 24	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24747641
HCN4	16882	10021	Brugada syndrome 8; Sick sinus syndrome 2	AD	Pediatric		Cardiovascular	Cardiovascular; Pharmacogenomic		Mutations may result in several cardiac conditions involving arrhythmia, and, depending on the condition, surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial;  Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever	8750801; 12750403; 15123648; 16407510; 17646576; 19165230; 20301690
HCRT	4847	3060	Narcolepsy 1	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10973318
HDAC4	14063	9759	Brachydacytly-mental retardation syndrome	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General	An individual with, among other manifestations, cardiovascular anomalies and sensorineural hearing loss, has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20691407
HDAC6	14064	10013	Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia	XL	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16001442; 20181727
HDC	4855	3067	Tourette's syndrome	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20445167
HEPACAM	26361	220296	Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation; Megalencephalic leukoencephalopathy with subcortical cysts 2A	AD/AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20517947; 21419380
HERC2	4868	8924	Skin/hair/eye pigmentation 1; Mental retardation, autosomal recessive 38	AD/AR	N/A	N/A	Dermatologic; Neurologic	General		Skin/hair/eye pigmentation 1 may not have clinical relevance, but may act a susceptibility factor locus for a multifactorial disease (melanoma); For Nonsyndromic intellectual disability, autism, and gait disturbance, genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17952075; 18172690; 18252221; 18252222; 21471978; 21926416; 22065085; 22234890; 23065719 
HES7	15977	84667	Spondylocostal dysostosis 4, autosomal recessive	AR	N/A	N/A	Musculoskeletal; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18775957; 20087400; 20301771
HESX1	4877	8820	Pituitary hormone deficiency, combined; Septooptic dysplasia	AR/AD	Pediatric		Endocrine; Neurologic; Ophthalmologic	Endocrine		Some individuals may have life-threatening adrenal insufficiency as well as additional endocrine insufficiency, and early recognition and immediate and long-term treatment can be beneficial	8696006; 9620767; 11136712; 14561704; 12519827; 16940453; 22145475 
HEXA	4878	3073	Tay-Sachs disease; GM2-gangliosidosis; Hexosaminidase A deficiency	AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5793973; 175770; 3375249; 2848800; 2140574; 2220809; 2824459; 2137287; 9090523; 15557512; 15714079; 15108204; 15956171; 20301397; 21937992; 21967858; 22441121; 22723944; 22789865 
HEXB	4879	3074	Sandhoff disease	AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Substrate reduction therapy has been described as potentially beneficial; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5651108; 571983; 3017984; 2948136; 8357844; 15956171; 18758829; 19898952; 20798201; 21150067; 22789865; 22848519; 23046579; 23113155 
HFE	4886	3077	Hemochromatosis	AR/Digenic	Pediatric		Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic	Biochemical; Gastrointestinal; Hematologic	Heterozygotes may display mild manifestations in some circumstances; Digenic inheritance (with HAMP) has been described	Interventions such as phlebotomy (including when presymptomatic) and dietary measures may be effective, though there is some controversy regarding specifics	678784; 3979748; 4058506; 3658574; 2919850; 2346731; 1614776; 8419246; 8051482; 8943161; 8696333; 9132598; 9867745; 9867746; 9792863; 9687253; 11336458; 10401000; 10471457; 11069625; 11087882; 10673305; 10673304; 11260010; 11386022; 11423500; 11325323; 11565552; 12915468; 14618419; 15024747; 15347835; 15175440; 15466004; 15657376; 18061062; 18566337; 18809761; 19214511; 20843714; 21901659; 21411349;  22265917; 22196777; 20301613
HFE2	4887	148738	Hemochromatosis, type 2A	AR	Pediatric		Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic	Biochemical; Gastrointestinal; Hematologic	Variants may also modify the severity of HFE-related hemochromatosis	Patients may benefit from surveillance related to iron overload, and from interventions such as venesection; Certain agents should be avoided (eg, alcohol consumption; iron-containing compounds; uncooked seafood); Hormone therapy may be beneficial in order to prevent osteoporosis	10205270; 12891378; 14982873; 15254010; 14982867; 14647275; 15461631; 15811010; 17847004; 18492090; 19796184; 20301349 
HFM1	20193	164045	Premature ovarian failure 9	AR	Pediatric		Endocrine; Obstetric	Obstetric		Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency	24597873
HGD	4892	3081	Alkaptonuria	AR	Pediatric		Biochemical; Cardiovascular; Musculoskeletal; Renal	Biochemical; Cardiovascular; Musculoskeletal; Renal		The condition can include cardiac complications, and surveillance for early detection and management of manifestations such as aortic dilatation, valvular disease, or coronary artery calcification may be beneficial; Awareness of complications including urolithiasis and joint degeneration may allow prompt recognition and treatment; Other, more specific therapies are under investigation	12784973; 5472968; 2667832; 2771520; 2270175; 2316305; 8782815; 9154114; 9529363; 9809834; 10482952; 10594001; 11001939; 10970188; 10945668; 12359141; 12501223; 12872815; 15260431; 20301627; 21620748; 21927854; 22482092; 22772574; 23035044; 23357094; 23353776; 23430897; 23430917; 23438536; 23466771; 23486607; 23619548; 23879342; 24009934; 24009959
HGF	4893	3082	Deafness, autosomal recessive 39	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	14512973; 19576567 
HGSNAT	26527	138050	Mucopolysaccharidosis type IIIC (Sanfilippo syndrome C)	AR	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Gastrointestinal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	33384; 3142713; 16960811; 17033958; 18024218; 18518886; 19479962; 20583299; 20825431
HIBCH	4908	26275	3-hydroxyisobutryl-CoA hydrolase deficiency	AR	Pediatric		Biochemical;Neurologic	Biochemical		Dietary measures (eg, low-protein, high carbohydrate) especially in ketosis, as well as medical treatment (eg, carnitine) may be beneficial)	7122152; 17160907
HK1	4922	3098	Hemolytic anemia, nonspherocytic, due to hexokinase deficiency	AR	Pediatric	Allelic with Neuropathy, motor and sensory, Russe type (Charcot-Marie-Tooth disease type 4G) (AR)	Hematologic; Neurologic; Ophthalmologic	Hematologic		Individuals may manifest with severe hemolysis, and anemia may be sufficiently severe to require splenectomy	6015552; 27532; 7234862; 6848140; 7655856; 12393545; 19536174; 19608687; 22978647
HLA-A	4931	3105	Drug-induced toxicity, susceptibility to	AD	Pediatric		General	Pharmacogenomic		Susceptibility to adverse reactions (including Stevens-Johnson syndrome), may have pharmacogenomic relevance related to a number of medications, including allopurinol, carbamazepine; HIV disease, progression in	15743917; 17258541; 21149285; 21428768; 21428769
HLA-B	4932	3106	Drug-induced toxicity, susceptibility to	AD	Pediatric		General	Pharmacogenomic		Susceptibility to adverse reactions (including Stevens-Johnson syndrome),  may have pharmacogenomic importance related to a number of medications, including abacavir, allopurinol, carbamazepine, flucocloxacillin	3477129; 16415921; 16538176; 17258541; 19933789; 203459391; 21244392; 21428768; 21676164; 22348415; 22348435 
HLCS	4976	3141	Holocarboxylase synthetase deficiency	AR	Pediatric		Biochemical; Dermatologic; Neurologic; Ophthalmologic	Biochemical		Biotin therapy can be beneficial to treat severe manifestations (which can include findings such as  alopecia, keratoconjunctivitis, lactic acidosis,  perioral erosions, and seizures), though the degree of response varies	6798072; 6794361; 6114319; 6790844; 6133032; 8319716; 7842009; 8817339; 9128289; 10190325; 11735028; 12124727; 12855220; 16134170; 16231399; 20095979; 21874615 
HMBS	4982	3145	Hydroxymethylbilane synthase deficiency; Porphyria, acute intermittent	AD/AR	Pediatric		Biochemical; Endocrine; Gastrointestinal; Hematologic; Neurologic; Oncologic	Biochemical; Endocrine; Gastrointestinal; Pharmacogenomic; Oncologic	Homozygosity/compound heterozygosity results in a distinct and much more severe phenotype	Attacks may be precipitated by porphyrinogenic agents (eg, barbiturates, sulfonamides), which, along with other exacerbating factors (eg, alcohol, infection) should be avoided; Endocrinological interventions may be beneficial in affected females; Acute attacks can be managed with supportive care (including TPN if necessary), and with medical treatment (eg, hematin); Surveillance for complications (eg, hepatocellular carcinoma) is indicated; Liver transplant has been reported as effective	13354248; 14198005; 4907358; 1106284; 329053; 665312; 87561; 449661; 7251856; 7258864; 6878621; 6433194; 2864531; 3724815; 3595653; 2789372; 2563167; 2246851; 2246852; 1577472; 7866402; 9199558; 10343207; 9860299; 10453740; 11071386; 14970743; 15001330; 15534187; 16211556;  17298217; 18627369; 18647325; 19460837; 19656452; 20301372; 22748422
HMGB3	5004	3149	Microphthalmia, syndromic 13	XL	N/A	N/A	Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4998085; 24993872
HMGCL	5005	3155	3-hydroxy-3-methylglutaryl-CoA lyase deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		Treatment to prevent and efficiently treat metabolic decompenstation can be beneficial; Avoidance of prolonged fasting and chronic low-fat, protein (including leucine)-restricted diet with carnitine supplementation can be beneficial	1256504; 1000856; 91680; 85928; 6156427; 6112838; 6489380; 6475954; 3099065; 3128690; 2246860; 8440722; 8617516; 11129331; 17692550; 19177531; 19932602 
HMGCR	5006	3156	Statins, efficacy of	AD	Pediatric		General	Pharmacogenomic		Selection and dosage of cholesterol-lowering medications may be impacted by genotyping results	15199031; 15367547; 24001602
HMGCS2	5008	3158	3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		Specific dietary measures (especially avoidance of fasting) as well as other treatments may be beneficial, both in well and decompensated state	9337379; 9727719; 11228257; 11479731; 16601895
HMOX1	5013	3162	Heme oxygenase 1 deficiency	AR	N/A	N/A	Allergy/Immunology/Infectious; Craniofacial; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Renal	Allergy/Immunology/Infectious; Hematologic 		Although the disease may ultimately be fatal, the condition includes immunodeficiency (includind due to asplenia), and prophylaxis and prompt and aggressive treatment of infections may be beneficial; RBC transfusions may be indicated for anemia	9884342; 21088618; 22023467 
HMX1	5017	3166	Oculoauricular syndrome	AD	N/A	N/A	Craniofacial; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18423520; 21417677 
HNF1A	11621	6927	Renal cell carcinoma, nonpapillary clear cell; Liver adenomatosis; Maturity onset diabetes of the young, type III	AD	Pediatric	Mutations may also cause or be associated with Diabetes mellitus, as in Diabetes mellitus, insulin-dependent, 20 (AD)	Endocrine; Oncologic	Endocrine; Oncologic		Surveillance and early detection of and treatment for neoplasms (eg, including renal and/or hepatic neoplasms) may decrease morbidity and mortality; Individuals with MODY-3 have been reported as presenting in childhood with macrosomia and hyperinsulinism, which has been reported as diazoxide-responsive 	8945470; 9313763; 10482964; 11058894; 10649494; 11575290; 11668618; 11904371; 12050210; 12355088; 12355088; 14598263; 15001650; 15649945; 21120312; 21683639; 22517943; 22802087 
HNF1B	11630	6928	Renal cell carcinoma, nonpapillary chromophobe	AD	Adult	Allelic with Renal cysts and diabetes syndrome (AD) 	Endocrine; Genitourinary; Oncologic; Renal	Oncologic		Surveillance and early detection of and treatment for malignancy may decrease morbidity and mortality	7151342; 2624270; 9398836; 10484768; 11085914; 12161522; 12675839; 15068978; 16249435; 15649945; 21380624; 21617276; 21767339; 22587559; 22269832; 22432796; 22706971
HNF4A	5024	3172	Congenital hyperinsulinism, diazoxide-responsive; Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young; Maturity onset diabetes of the young, 1	AD	Pediatric	Mutations may also cause or be associated with Diabetes mellitus, insulin dependent (AD)	Endocrine; Renal	Endocrine; Renal		Individuals can present in childhood with macrosomia and hyperinsulinism, which has been reported as diazoxide-responsive; For individuals whose phenotype includes Fanconi syndrome, awareness may allow prompt treatment through replacement of lost solutes	8945471; 9313765; 9294105; 9449683; 9920109; 11232004; 12050210; 17407387; 21683639; 21922456; 22802087; 24285859
HNRNPA1	5031	3178	Amyotrophic lateral sclerosis 19; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3	AD	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20116073; 23455423
HNRNPA2B1	5033	3181	Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2	AD	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23455423
HNRNPDL	5037	9987	Limb-girdle muscular dystrophy, type 1G	AD	N/A	N/A	Musculoskeletal; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24647604
HOGA1	25155	112817	Hyperoxaluria, primary, type III	AD/AR	Pediatric		Biochemical; Renal	Renal		Increased fluid intake in order to promote hydration as well as medical therapy (eg, neutral phosphate therapy, citrate medications, thiazides) may be beneficial	20797690; 21896830; 22781098; 22688746; 22391140 
HOXA1	5099	3198	Athabaskan brainstem dysgenesis syndrome; Bosley-Salih-Alorainy syndrome	AR	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Neurologic	Audiologic/Otolaryngologic	The conditions can involve multiple congenital anomalies	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	16155570; 18412118; 20075099 
HOXA11	5101	3207	Radioulnar synostosis with amegakaryocytic thrombocytopenia	AD	Pediatric		Hematologic; Musculoskeletal	Hematologic		Individuals can have symptomatic thrombocytopenia and bone marrow failure manifesting in the neonatal period, requiring early bone marrow/umbilical cord stem cell transplantation	11101832; 11442476; 16765069; 20562651 
HOXA13	5102	3209	Hand-foot-genital syndrome; Guttmacher syndrome; Hand-foot-uterus syndrome	AD	N/A	N/A	Genitourinary; Musculoskeletal; Renal	Renal	The conditions can involve multiple congenital anomalies	The disorder may be recognizable in the majority of individuals, but individuals are at risk of renal findings such as unrecognized vesicoureteral reflux, which can cause renal damage, and prophylactic/treatment measures can be beneficial	5450271; 8484413; 9020844; 10839976; 11968094; 12073020; 12414828; 12676922; 19591980; 20301596; 21549968 
HOXA2	5103	3199	Microtia, hearing impairment, and cleft palate	AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal	Audiologic/Otolaryngologic	The condition may be recognizable from manifestations ascertained through physical examination	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	18394579
HOXB1	5111	3211	Facial paresis, hereditary congenital, 3	AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Neurologic; Ophthalmologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	22770981
HOXC13	5125	3229	Ectodermal dysplasia 9	AR	N/A	N/A	Dermatologic	General		Males have been described as being affected with genitourinary anomalies, some of which require interventions; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23063621
HOXD10	5133	3236	Vertical talus, congenital	AD	N/A	N/A	Musculoskeletal	General	One described family was also affected by Charcot-Marie-Tooth disease	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15146389; 16450407
HOXD13	5136	3239	Brachydactyly-syndactyly syndrome; Brachydactyly, type D; Brachydactyly, type E1; Syndactyly, type V; Synopolydactyly, type I, Synopolydactyly, type II; Synopolydactyly with clefting, autosomal recessive	AD/AR	N/A	N/A	Craniofacial; Musculoskeletal	Renal	The condition has also been implicated in VACTERL association (AD), but the pathogenesis is unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7666393; 8817328; 8614804; 8933344; 9758628; 11778160; 12116248; 12649808; 12900906; 16222680; 17236141; 19006232; 18177473; 19060004; 20974300; 21814222; 22233338; 22373878; 22374128; 22406499; 22473151 
HP	5141	3240	Anhaptoglobinemia; Hypohaptoglobinemia	AR	Pediatric		Hematologic	Hematologic		Variants may be important in specific situations (eg, related to transfusion)	9463309; 10666182; 14999562
HPD	5147	3242	Tyrosinemia, type III; Hawksinuria	AD/AR	Pediatric		Biochemical; Neurologic	Biochemical	It is unclear if a strict low tyrosine diet alters the natural history of tyrosinemia type III, though some have suggested that treatment may be important, especially in infancy	In Tyrosinemia III, specific dietary measures (eg, restriction of phenylalanine and tyrosine) are recommended; In Hawksinuria, individuals may present with manifestations including failure to thrive, and a protein-restricted diet has been reported as beneficial in some instances	1130176; 858207; 7278885; 6828337; 6132360; 1519651; 9343288; 10412819; 10942115; 11073718; 11916315; 17560158 
HPGD	5154	3248	Hypertrophic osteoarthropathy, primary, autosomal recessive 1; Cranioosteoarthropathy; Digital clubbing, isolated congenital 	AR	Pediatric	Allelic  Digital clubbing, isolated congenital  (AR)	Musculoskeletal	General		Medical treatment (eg, with sulfasalazine, methotrexate) has been described as beneficial related to joing manifestations	9402870; 17551338; 17285282; 18500342; 18805827; 19306095; 19568269; 20299379; 20406614; 21426412; 24533558
HPRT1	5157	3251	Kelley-Seegmiller syndrome; Lesch-Nyhan syndrome	XL	Pediatric		Biochemical; Hematologic; Musculoskeletal; Neurologic; Renal	Biochemical; Renal	In Lesch-Nyhan syndrome, an allelic condition, as in Kelley-Seegmiller syndrome, control of uric acid production can be effective to reduce sequelae, but does not affect Neurological manifestations	Treatments related to uric acid overproduction, such as alkalinization and allopurinol,  can be effective in order to prevent and treat sequelae such as renal dysfunction and gouty arthritis	14142409; 4291947; 4322125; 3600927; 10657589; 11891689; 20301328; 20558399 
HPS1	5163	3257	Hermansky-Pudlak syndrome 1	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pulmonary	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pharmacogenomic;  Pulmonary		Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination; Surveillance related to ophthalmologic, gastrointestinal, and other manifestations has been recommended in all individuals with HPS; Lung transplantation has been described	3921802; 2916560; 8896559; 9562579; 9497254; 10411151; 10768343; 11414528; 12126938; 16210149; 19398212; 19729668; 20301464; 20514622; 20662851; 21833017
HPS3	15597	84343	Hermansky-Pudlak syndrome 3	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pulmonary	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic		Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination; Surveillance related to ophthalmologic, gastrointestinal, and other manifestations has been recommended in all individuals with HPS	11455388; 20301464
HPS4	15844	89781	Hermansky-Pudlak syndrome 4	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pulmonary	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pharmacogenomic;  Pulmonary		Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination; Surveillance related to ophthalmologic, gastrointestinal, and other manifestations has been recommended in all individuals with HPS	11836498; 20301464; 21833017 
HPS5	17022	11234	Hermansky-Pudlak syndrome 5	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pulmonary	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic		Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination; Surveillance related to ophthalmologic, gastrointestinal, and other manifestations has been recommended in all individuals with HPS	12548288; 20301464; 21833017 
HPS6	18817	79803	Hermansky-Pudlak syndrome 6	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pulmonary	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic		Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination; Surveillance related to ophthalmologic, gastrointestinal, and other manifestations has been recommended in all individuals with HPS	12548288; 20301464
HPSE2	18374	60495	Ochoa syndrome; Urofacial syndrome 1	AR	Pediatric		Craniofacial; Neurologic; Renal	Renal		Individuals are at high risk of infantile-onset vesicoureteral reflux leading to kidney damage, hypertension, and eventual renal failure, and surveillance and preventive measures related to manifestations such as urinary tract/renal infections may be beneficial	11446407; 19839856; 19669792; 20560209; 20560210; 20605127; 21332471; 21450525
HR	5172	55806	Hypotrichosis 4; Atrichia with papular lesions; Alopecia universalis congenita	AD/AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13150805; 13763141; 5570254; 9758627; 10205263; 10827399; 11410842; 12271294; 11982770; 12880440; 17869066; 10417283; 11069461; 10854110; 10777357; 15149494; 17680008; 19122663; 20659777; 20814945; 21272494; 21919222; 22584530 
HRAS	5173	3265	Costello syndrome; Congenital myopathy with excess of muscle spindles	AD	Pediatric		Cardiovascular; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic; Oncologic	Cardiovascular; Oncologic		The condition may be frequently clinically recognizable, but often includes cardiovascular manifestations, including  structural anomalies, hypertrophic cardiomyopathy, and arrhythmias, as well as an elevated risk for malignancy, and surveillance and appropriate care may be beneficial	907573; 8882404; 8834040; 9863604; 9521961; 10424828; 10449656; 10678668; 11857557; 11857556; 12210337; 12561057; 12605434; 16170316; 15940703; 16372351; 16329078; 16969868; 16443854; 17551924; 17412879; 17054105; 18042262; 18247425; 18302240; 19213030; 19288554; 19206176; 20301680; 20425820; 21438134; 21495179; 21834037; 22098123; 22261753; 22420426; 22488832; 22495831; 22495892; 22510203; 22887473; 22926243; 23429430; 23751039; 23813656; 23918324; 24057668
HRG	5181	3273	Thrombophilia due to histidine-rich glycoprotein deficiency	AD	Adult		Hematologic	Hematologic	Elevated histidine-rich glycoprotein (HRG) has also been described as associated with risk of thromboembolism	Individuals are at risk for thromboembolic events.and related sequelae, and knowledge may allow preventive measures as well as prompt treatment of manifestations	3689697; 8236132; 7769366; 8815595; 11057869 
HS6ST1	5201	9394	Hypogonadotropic hypogonadism 15, with or without anosmia	AD/AR/Digenic/Multigenic	Pediatric		Endocrine; Musculoskeletal; Neurologic	Endocrine	Relatively complex models of inheritance such as digenic inheritance and interaction with other related loci (eg, FGF8-network-associated genes) have been described	Surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to male fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	21700882; 23643382
HSD11B1	5208	3290	Cortisone reductase deficiency 1	AD/AR (Triallelic)	N/A	N/A	Endocrine	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3990293; 8923828; 10522997; 12858176; 21325058
HSD11B2	5209	3291	Cortisol 11-beta-ketoreductase deficiency	AR	Pediatric		Endocrine; Renal	Renal		There is a broad range of severity, including potentially lethal early chidlhood disease, and medical treatment (eg, with spironolactone) can be beneficial	870517; 1740492; 3460996; 3164727; 8370690; 7670488; 9683587; 9707624; 10536001; 10523339; 17314322; 19909806
HSD17B10	4800	3028	17-beta-hydroxysteroid dehydrogenase X deficiency; Mental retardation, X-linked syndromic 10	XL	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Neurologic 	General	Dietary measures (eg, isoleucine restriction) and medications (eg, benzhexol, mitochondrial cocktails), have been reported, but the overall efficacy has been decribed as ineffective; Mental retardation, X-linked syndromic 10 has been described as distinct from 17-beta-hydroxysteroid dehydrogenase X deficiency	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10521307; 11102558; 12112118; 12555940; 12696021; 12872843; 14729408; 15059617; 16148061; 17236142; 19706438; 20664630; 22132097; 22127393 
HSD17B3	5212	3293	17-Beta hydroxysteroid dehydrogenase III deficiency	AR	Pediatric		Endocrine; Genitourinary	Endocrine; Genitourinary		Prepubertal diagnosis may allow surgical treatment via removal of  abnormal testes, preventing typical presenting clinical signs in puberty (marked masculinization and hirsutism)	2998649; 8075637; 8550739; 10599740; 21700882; 22212252; 22594312; 22445608; 22876557 
HSD17B4	5213	3295	Perrault syndrome	AR	Pediatric	Allelic with D-bifunctional protein deficiency (AR)	Audiologic/Otolaryngologic; Biochemical; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Obstetric	Audiologic/Otolaryngologic	The condition may be clinically recognizable in females, and the exact onset of hearing loss is unclear, but evidence suggests a prelingual onset	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	4061497; 2868085; 2882519; 2921319; 2122104; 1357231; 8147505; 8279468; 9482850; 9915948; 10400999; 11992265; 11743515; 15216544; 16385454; 20673864; 23181892; 24553428
HSD3B2	5218	3284	3-beta-hydroxysteroid dehydrogenase, type II deficiency	AR	Pediatric		Endocrine; Genitourinary	Endocrine		Adrenal replacement can be effective, though individuals may nevertheless demonstrate severe manifestations	13968789; 295036; 3088022; 2826919; 1309452; 1363812; 14764797; 18252794; 24553428
HSD3B7	18324	80270	Bile acid synthesis defect, congenital, 1	AR	Pediatric		Gastrointestinal	Gastrointestinal		Due to early-onset progressive hepatic disease, affected invididuals commonly present in infancy with  failure to thrive and coagulopathy, and typically demonstrate a favorable response to medical treatment (with oral bile acid therapy)	3470305; 11067870; 12679481; 22095780
HSF4	5227	3299	Cataract 5, multiple types	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3233780; 12089525; 18941546; 19014451; 20670914 
HSPA1L	5234	3305	Abacavir, susceptibility to toxicity with	AD 	Pediatric		General	Pharmacogenomic		Medication choice and administration may be affeted by the presence of variants	11943262; 11888582; 15024131
HSPB1	5246	3315	Neuropathy, distal hereditary motor, type IIB; Charcot-Marie-Tooth disease, axonal, type 2F 	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11528513; 15122254; 16087758; 18325928; 18832141; 18952241; 20301462; 20870250; 22176143 
HSPB3	5248	8988	Neuronopathy, distal hereditary motor, type IIC	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20142617
HSPB8	30171	26353	Charcot-Marie-Tooth disease, axonal, type 2L; Distal hereditary motor neuronopathy IIA	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1517763; 15122253; 15021985; 15565283; 18325928; 20538880; 21985219 
HSPD1	5261	3329	Spastic paraplegia-13; Leukodystrophy, hypomyelinating, 4	AD/AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10677329; 11898127; 17420924; 18571143
HSPG2	5273	3339	Schwartz-Jampel syndrome, type 1	AD/AR	Pediatric	Allelic with Dyssegmental dysplasia, Silverman-Handmaker type (AR)	Craniofacial; Musculoskeletal	General; Pharmacogenomic		An increased risk of malignant hyperthermia has been described; Variants may have additional pharmacogenomic importance (eg, related to tardive dyskinesia); Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13909723; 4953364; 11101850; 11038441; 11279527; 11941538; 16927315; 20072119; 20542149; 21808285 
HTR1A	5286	3350	Periodic fever, menstrual cycle dependent	AD	Pediatric		Allergy/Immunology/Infectious; Endocrine; Obstetric	Allergy/Immunology/Infectious	As the disorder affects females, the onset may be in the pediatric timeframe due to the typical age of menarche, though reported individuals have been typically described as older	Fevers have been reported as responding to medical treatments such as HTR1A-agonists	21990073
HTR2A	5293	3356	Major depressive disorder, response to citalopram therapy in; Clozapine, response to	AD	Pediatric		General	Pharmacogenomic		Variants may relate to the efficacy of medications such as Citalopram and clozapine	9491814; 12563180; 16642436
HTRA1	9476	5654	Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL)	AR	N/A	N/A	Cardiovascular; Dermatologic; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17053108; 17053109; 17884985; 17568988; 18511946; 19387015; 20437615; 21115960; 21482952; 22900900 
HTT	4851	3064	Huntington disease	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2992086; 2881213; 8401589; 8401587; 8458085;  8401588; 7826277; 8659522; 9150168; 11553930; 12791042; 16096998; 17240289; 19776381; 19455596
HUWE1	30892	10075	Mental retardation, X-linked syndromic, Turner type	XL	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7943042; 18252223; 23721686
HYAL1	5320	3373	Mucopolysaccharidosis type IX	AR	N/A	N/A	Biochemical; Craniofacial; Dermatologic; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8793927; 10339581
HYLS1	26558	219844	Hydrolethalus syndrome	AR	N/A	N/A	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Pulmonary	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7028327; 15843405; 18648327 
IARS2	29685	55699	Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia (CAGSSS)	AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial;  Endocrine; Musculoskeletal; Ophthalmologic; Neurologic	Audiologic/Otolaryngologic; Endocrine		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Awareness of growth hormone deficiency may allow early recognition and treatment	8409271; 25130867
IBA57	27302	200205	Multiple mitochondrial dysfunctions syndrome 3	AR	N/A	N/A	Biochemical; Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23462291
ICAM4	5347	3386	Blood group, Landsteiner-Wiener	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	7632968; 8639917
ICK	21219	22858	Endocrine-cerebroosteodysplasia	AR	N/A	N/A	Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19185282
ICOS	5351	29851	Immunodeficiency, common variable, 1	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis (including with administration of IVIG) and early and aggressive treatment of infections may be beneficial	12577056; 15507387; 18424338; 19426217; 20301476; 21970952 
IDH2	5383	3418	D-2-hydroxyglutaric aciduria 2	AD	N/A	N/A	Biochemical; Cardiovascular; Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20847235
IDH3B	5385	3420	Retinitis pigmentosa, autosomal recessive, IDH3B-related	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18806796
IDS	5389	3423	Mucopolysaccharidosis type II	XL	Pediatric		Biochemical; Cardiovascular	Biochemical		Enzyme replacement therapy is available and may positively influence biochemical parameters and some outcomes (such as height and endurance), but there is not evidence that the outcome would be positively affected with earlier (genetic) diagnosis, and replacement may not affect neurologic (CNS) manifestations; Awareness of multisystemic involvement, including cardiac manifestations, may allow early and beneficial management of sequelae such as cardiac valvular disease; BMT has been reported	4622960; 1901826; 1906048; 1303211; 8111411; 7581397; 8940265; 9660053; 9762601; 9501270; 9921913; 10399096; 16912578; 17185020; 18038146; 19901005; 19748810; 20301451; 21502868; 23497636; 23537841
IDUA	5391	3425	Mucopolysaccharidosis type I	AR	Pediatric		Biochemical; Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary	Biochemical	The condition includes a wide degree of severity, and multiple subtypes, including Scheie syndrome, Hurler-Scheie syndrome, and Hurler syndrome	Enzyme replacement therapy, the timing of which affects outcome is available, but may not affect cerebral manifestations; HSCT in selected children with severe MPS I before age two years can be beneficial	6139633; 9516162; 7550242; 11735025; 11172140; 15128896; 19748810; 20301341; 21502868
IER3IP1	18550	51124	Microcephaly, epilepsy, and diabetes syndrome	AR	N/A	N/A	Endocrine; Neurologic	General	Individuals may have early-onset diabetes, which may be difficult to control 	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16972080; 21835305
IFIH1	18873	64135	Aicardi-Goutieres syndrome 7	AD	N/A	N/A	Allergy/Immunology/Infectious; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24686847; 24995871; 25243380
IFITM5	16644	387733	Osteogenesis imperfecta, type V	AD	N/A	N/A	Craniofacial; Musculoskeletal	General	Pamidronate treatment has been described as beneficial in terms of reducing fracture risk, but the advantage of early (genetic) diagnosis is unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10976985; 16162424; 22863190; 22863195; 23408678; 23612438; 23674381; 23813632
IFNGR1	5439	3459	Immunodeficiency 27B Immunodeficiency 27A	AD/AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may be susceptible to frequent and severe mycobacterial infections, and awareness and early and aggressive treatment of infections may be beneficial; Consideration of potential adverse effects of BCG vaccination in some individuals may be beneficial	8960475; 8960473; 9389728; 10192386
IFNGR2	5440	3460	Immunodeficiency 28	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may be susceptible to frequent and severe mycobacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	15924140; 23161749 
IFNL3	18365	282617	Drug metabolism, IL28B-related	AD	Pediatric		General	Pharmacogenomic		Variants may have pharmacogenomic importance, as selection and dosing of medications (including peg-interferon and ribavirin) may be affected by the presence of variants	19684573; 19749758; 19749757; 19759533; 21254158; 21993426; 21443535; 21951981 
IFT122	13556	55764	Cranioectodermal dysplasia 1; Sensenbrenner syndrome	AR	N/A	N/A	Craniofacial; Dental; Dermatologic; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17022080; 19760620; 20493458
IFT140	29077	9742	Short-rib thoracic dysplasia 9 with or without polydactyly	AR	N/A	N/A	Musculoskeletal; Neurologic; Ophthalmologic; Renal	General		Mutations may modify ciliopathies due to mutations in other genes; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22503633; 23418020 
IFT172	30391	26160	Short -rib thoracic dysplasia 10 with or without polydactyly	AR	N/A	N/A	Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Renal transplantation has been desribed; The conditions may involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24140113
IFT27	18626	11020	Bardet Biedl syndrome 19	AR	N/A	N/A	Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition frequently involves multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24488770
IFT43	29669	112752	Cranioectodermal dysplasia 3	AR	N/A	N/A	Craniofacial; Dental; Dermatologic; Musculoskeletal; Renal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21378380
IFT80	29262	57560	Short-rib thoracic dysplasia 2 with or without polydactyly	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17468754; 19610081; 19648123 
IFT88	20606	8100	Ciliopathy, IFT88-related	AR	N/A	N/A	Gastrointestinal; Neurologic; Renal	General		Individuals may have renal and hepatic manifestations in this reported lethal disorder; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22941275
IGBP1	5461	3476	Corpus callosum, agenesis of, with mental retardation, ocular coloboma and micrognathia	XL	N/A	N/A	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14556245
IGF1	5464	3479	Insulin-like growth factor I deficiency	AR	Pediatric		Audiologic/Otolaryngologic; Endocrine; Neurologic	Audiologic/Otolaryngologic; Endocrine		Recombinant human IGF1 treatment has been reported to improve linear growth and insulin sensitivity; Interventions related to hearing impairment may also be beneficial 	8857020; 10323388; 10770174; 14684690; 20668042; 21237682; 22832530 
IGF1R	5465	3480	Insulin-like growth factor I, resistance to	AD/AR	Pediatric		Endocrine	Endocrine	Bi-allelic mutations have been described as resulting in a more severe phenotype	Individuals may manifest with severe growth deficiency, and growth hormone therapy (starting at a relatively early age) can be beneficial	14657428; 22998174; 22130793; 23045302
IGFALS	5468	3483	Insulin-like growth factor-binding protein, acid-labile subunit, deficiency of	AR	Pediatric		Endocrine	Endocrine		As growth hormone treatment has not been reported as being effective in this condition, genetic diagnosis may be beneficial in terms of pursuing optimal management	14762184; 17726072; 21396577; 21664162; 23488611
IGFBP7	5476	3490	Retinal arterial macroaneurysm with supravalvular pulmonic stenosis	AR	N/A	N/A	Cardiovascular; Ophthalmologic	General	Argon laser photocoagulation of the retinal macroaneurysms has been described as resulting in clinical improvement in some individuals; Surgical repair of pulmonic stenosis may be indicated in some individuals	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12441727; 21835307
IGHM	5541	3507	Agammaglobulinemia 1	AR	Pediatric		Allergy/Immunology/Infectious; Gastrointestinal	Allergy/Immunology/Infectious		Antiinfectious prophylaxis (including with administration of IVIG) and early and aggressive treatment of infections may be beneficial	8890099; 12370281; 21039741 
IGHMBP2	5542	3508	Spinal muscular atrophy, distal, autosomal recessive, 1	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11528396; 14681881; 15290238; 16458836; 16765827; 17431882; 20859832; 21353777; 22157136 
IGKC	5716	3514	Immunoglobulin kappa light chain deficiency	AR	N/A	N/A	General	General		The clinical relevance is unclear	4117311; 812574; 815819; 3931219
IGLL1	5870	3543	Agammaglobulinemia 2	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis (including with administration of IVIG) and early and aggressive treatment of infections may be beneficial	9419212; 10077633; 10590911 
IGSF1	5948	3547	Central hypothyroidism and testicular enlargement	XL	Pediatric		Endocrine;Genitourinary; Neurologic	Endocrine		Individuals can demonstrate a number of endocrine deficiencies (including central hypothyroidism, as well as growth hormone deficiency), for which hormone replacement therapy may be beneficial	23143598
IHH	5956	3549	Acrocapitofemoral dysplasia; Brachydactyly, type A1 	AD/AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8592325; 11455389; 12384778; 32327,; 12525541; 15886999; 16871364; 17486609; 18629882; 22406540 
IKBKAP	5959	8518	Dysautonomia, familial	AR	N/A	N/A	Craniofacial; Neurologic; Renal	General	One report has described possible increased tumorigenesis in affected individuals; Individuals may be prone to injury due to pain insensitivity	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18118947; 14071043; 14245781; 4322121; 7374014; 7254974; 7097419; 3585611; 11179021; 11179008; 12406829; 12546638; 15088259; 19651702; 19914433; 20301359; 22129610; 22170819; 22229594; 22571291; 22727867; 22739220; 22850346
IKBKB	5960	3551	Immunodeficiency 15	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may be susceptible to severe and recurrent infections, and prophylaxis and early and aggressive treatment of infections may be beneficial; BMT/HSCT has been described	24369075; 25216719
IKBKG	5961	8517	Immunodeficiency 33; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency; Immunodeficiency, isolated; Incontinentia pigmenti, type II; Invasive pneumococcal disease, recurrent, isolated, 2	XL	Pediatric		Allergy/Immunology/Infectious; Dental; Dermatologic; Neurologic; Ophthalmologic	Allergy/Immunology/Infectious; Craniofacial; Dental; Ophthalmologic	In Ectodermal dysplasia, anhdyrotic/hypohidrotic, with immune deficiency, some individuals have been described as not responding well to preventive measures/treatment; Lung transplantation has been described	In Immunodeficiency 33 (Atypical mycobacteriosis), BCG vacine should be avoided, and recognition of potential sequelae of immunodeficiency may allow prompt diagnosis and treatment of infectious manifestations; In Ectodermal dysplasia, anhdyrotic/hypohidrotic, with immune deficiency, prophylactic measures relating to infectious complications, (eg, IVIG and  antibiotics) have in some individuals been described as improve clinical status when initiated early, and prompt and aggressive treatment of infections may be beneficial; In Isolated immunodeficiency, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; In Incontinentia pigmenti, type II, which may be clinically recognizable, fluorescein angiography has been recommended in order to diagnose ischemic retina in individuals with retinal changes, and early treatment with peripheral retinal photocoagulation may reduce the risk of retinal detachment; In IKBKG-related immunodeficiency such as Invasive pneumococcal disease, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	117248; 8923006; 10839543; 11047757; 11590134; 11242109; 11224521; 11241484; 12588226; 15577852; 15356572; 16228229; 16333836; 16532398; 16818673; 16950813; 20301645; 20829317; 21993693; 22453515
IL10	5962	3586	Graft vs. host disease	AD	Pediatric	 	General	Pharmacogenomic		In Graft vs. host disease, variants may have clinical relevance, as specific allele(s) shown to be a marker of favorable outcome following transplantation	14657422; 14657427; 20305143 
IL10RA	5964	3587	Inflammatory bowel disease 28, early onset, autosomal recessive	AR	N/A	N/A	Allergy/Immunology/Infectious; Gastrointestinal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19890111; 21519361; 22476154
IL10RB	5965	3588	Inflammatory bowel disease 25, early onset, autosomal recessive	AR	N/A	N/A	Allergy/Immunology/Infectious; Gastrointestinal	General	HSCT has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19890111; 21519361
IL11RA	5967	3590	Craniosynostosis and dental anomalies	AR	N/A	N/A	Craniofacial; Dental	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21741611
IL12B	5970	3593	Immunodeficiency 28; Immunodeficiency 29	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may be susceptible to severe and recurrent infections, including adverse sequelae from BCG vaccination, and prophylaxis and early and aggressive treatment of infections may be beneficial	9603732; 9789052; 11753820
IL12RB1	5971	3594	Immunodeficiency 30	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals have been described as susceptible to severe atypical mycobacterial infections (as well as other infections, including Salmonella, Cryptococcal, Coccidioides  infections), and prophylaxis and early and aggressive treatment of infections may be beneficial; Consideration of potential adverse effects of BCG vaccination in some individuals may be beneficial	9603732; 9603733; 12591909; 15736007; 21905505; 21258095; 22523911 
IL17F	16404	112744	Candidiasis, familial, 6	AD	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may manifest with chronic cutaneous candidiasis, and awareness may allow early detection and aggressive treatment of infections may be beneficial	21350122
IL17RA	5985	23765	Candiasis, familial, 5	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals have been described as susceptible to infections such as Candida albicans and Staph aureus dermatitis, and awareness may allow early detection and early and aggressive treatment of infections may be beneficial	21350122
IL17RD	17616	54756	Hypogonadotropic hypogonadism 18, with or without anosmia	AD/Digenic	Pediatric		Audiologic/Otolaryngologic; Dental; Endocrine; Musculoskeletal; Neurologic	Audiologic/Otolaryngologic; Endocrine	Relatively complex genetic models of disease have been described (eg, involving mutations in other FGF8-network-associated genes)	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required; Congenital hearing loss in individuals is typically (though not always) described as unilateral, and recognition and interventions related to speech and language development may be beneficial	23643382
IL1RAPL1	5996	11141	Mental retardation, X-linked 21/34	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8230164; 10471494; 16470793; 18005360; 19012350; 18801879; 21484992
IL1RN	6000	3557	Osteomyelitis, sterile multifocal, with periostitis and pustulosis	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic	Allergy/Immunology/Infectious		Individuals may present in infancy with manifestations including rash, pain, and oral lesions, which may advance to more severe findings such as progressive skin lesions, vasculitis, skeletal lesions, pulmonary disease, and severe inflammatory response syndrome, and medical treatment (eg, with anakinra) has been described as effective 	19494218; 19494219
IL21	6005	59067	Immunodeficiency, common variable, 11	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals have been described as manifesting with primary immunodeficiency (with sequelae including severe inflammatory bowel disease, as well as recurrent/severe respiratory infections) and recognition may allow prophylactic measures and early and aggressive treatment of infections	24746753
IL21R	6006	50615	Immunodeficiency, primary, autosomal recessive, IL21R-related	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may manifest with immunodeficiency, and prophylactic measures, as well as early and aggressive treatment of infections may be beneficial; HSCT has been described	23440042
IL2RA	6008	3559	Interleukin 2 receptor, alpha, deficiency of	AR	Pediatric		Allergy/Immunology/Infectious; Gastrointestinal	Allergy/Immunology/Infectious		Described individuals have an increased susceptibility to bacterial, fungal, and viral infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been described	9096364; 10879793 
IL2RG	6010	3561	Combined immunodeficiency, X-linked	XL	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections is indicated prior to attempts at immune reconstitution; Chronic immunoglobulin therapy may be required even after treatment aimed at immune reconstitution, which is necessary for survival; BMT/HSCT has been described, as has the use of gene therapy in individuals who are not candidates for or who have failed BMT	2243135; 7883965; 8462096; 9063412; 11517204; 11806989; 20301584; 21184155; 22460439 
IL31RA	18969	133396	Amyloidois, primary localized cutaneous, 2	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19663869; 19690585
IL36RN	15561	26525	Pustular psoriasis, generalized	AR	N/A	N/A	Allergy/Immunology/Infectious; Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21848462; 21839423; 22903787; 23698098
IL7R	6024	3575	Severe combined immunodeficiency, autosomal recessive, T-cell negative, B-cell positive, NK cell positive	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals are susceptible to frequent and severe bacterial, viral, fungal, and opportunistic infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT has been described	9843216; 11023514; 17827065; 21184155; 21625022; 21883749 
ILDR1	28741	286676	Deafness, autosomal recessive 42	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	15641023; 21255762; 23226338 
IMPAD1	26019	54928	Chondrodysplasia with joint dislocations, GPAPP type	AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21549340; 22903787
IMPDH1	6052	3614	Retinitis pigmentosa 10; Leber congenital amaurosis 11	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11875050; 11875049; 16384941; 20006823; 20238028; 20301475; 21791244 
IMPDH2	6053	3615	IMPDH2 enzyme activity, variation in	AD	Pediatric	 	Biochemical	Pharmacogenomic		Variants may be involved in response to treatment with medications such as mycophenolate mofetil in individuals who have undergone transplants	17496727
IMPG1	6055	3617	Macular dystrophy, vitelliform, 4	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23993198; 25085631
IMPG2	18362	50939	Retinitis pigmentosa 56	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20673862; 25085631
INF2	23791	64423	Glomerulosclerosis, focal segmental, 5 ; Charcot-Marie-Tooth disease, dominant intermediate E	AD	N/A	N/A	Neurologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20023659; 21415313; 22187985; 22961558; 22971997 
INPP5E	21474	56623	Joubert syndrome 1; Mental retardation, truncal obesity, retinal dystrophy, and micropenis (MORM syndrome)	AR	N/A	N/A	Endocrine; Genitourinary; Neurologic; Ophthalmologic; Renal	General	Individuals may have renal issues (though most reported individuals did not have evidence of compromised renal function)	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16493448; 19668216; 19668215
INPPL1	6080	3636	Opsismodysplasia	AR	Pediatric		Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Musculoskeletal; Pulmonary; Renal	Allergy/Immunology/Infectious; Cardiovascular; Pulmonary; Renal	The condition can involve multiple congenital anomalies	The condition may involve renal phosphate wasting in some individuals, and prompt detection may allow beneficial dietary/medical management; Many individuals manifest with respiratory insufficiency and frequent respiratory infections, and awareness may allow prompt diagnosis and treatment; Individuals may also demonstrate congenital anomalies affecting the cardiovascular, renal, and other systems, and awareness may allow early detection and management	12624139; 23273567; 23273569 
INS	6081	3630	Diabetes mellitus, permanent neonatal	AD	Pediatric	Allelic with Hyperproinsulinemia, familial, with or without diabetes (AD); Maturity onset diabetes of the young (AD)	Endocrine	Endocrine		Individuals may manifest in infancy with findings including intrauterine growth retardation, postnatal growth deficiency, and signs of diabetes mellitus (eg, hyperglycemia, glycosuria), as well as severe dehydration, and recognition can allow preventive measures related to potential sequelae, surveillance (eg, with blood glucose monitoring as well as surveillance for other common sequelae of diabetes mellitus affecting systems such as the renal and ophthalmogic systems); In the case of an acute diabetic crisis, rapid treatment (eg, with rehydration and IV insulin, transitioning to SQ insulin when stable) is indicated, though rapid-acting and (non-continuous) short-acting insulin preparations may result in severe hypoglycemia in young patients 	815812; 288074; 381941; 6424111; 3512591; 17855560; 18451997; 18162506; 18192540; 18171712; 20301620
INSL3	6086	3640	Cryptorchidism	AD	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11095425; 12601553; 12970298; 17028442; 17437853; 19416190 
INSR	6091	3643	Hyperinsulinemic hypoglycemia, familial, 5; Rabson-Mendenhall syndrome; Donohoe syndrome	AD/AR	Pediatric	Allelic with Diabetes mellitus, insulin-resistant, with acanthosis nigricans (AD/AR)	Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Dental; Dermatologic; Endocrine; Musculoskeletal; Oncologic; Renal	Allergy/Immunology/Infectious; Cardiovascular; Endocrine; Oncologic; Renal		Several affected individuals with familial hyperinsulinemic hypoglycemia have had severe sequelae, such as hypoglycemia-induced seizures, which could potentially be averted by early recognition and treatment; In Rabson-Mendenhall syndrome, due to the risk of infectious sequelae, early and aggressive treatment of infections can be beneficial; In Rabson-Mendenhall syndrome, effective treatment of insulin resistance can be difficult, but there are reports of the efficacy of leptin treatment; In Donohoe syndrome, medical (eg, diazoxide) and surgical treatments may be beneficial; Recognition may allow prompt treatment of other organ system involvement, such as related to cardiac manifestations (eg, cadiac hypertrophy, as recombinant human insulin-like growth factor-1 hs been reported as beneficial for treatment of hypertrophic cardiomyopathy and renal tubular dysfunction); Individuals with Donohue syndrome or Rabson-Mendenhall syndrome may be at increased risk of malignant processes (eg, breast and thyroid cancer have been described), and awareness may allow prompt detection and early treatment	13212592; 13302174; 2121734; 2544998; 3020345; 3322162; 3384956; 3415309; 3721065; 7815442; 8105179; 8288049; 8326490; 15070911; 15161766; 15232309; 17201797; 18405695; 18411068; 21869538; 22172957; 22563226; 22768670; 22972224; 23229189; 23347304; 23824322
INVS	17870	27130	Nephronophthisis 2	AR	N/A	N/A	Cardiovascular; Gastrointestinal; Neurologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2702088; 9792867; 12872123; 19177160; 20798123; 23559409
IQCB1	28949	9657	Senior-Loken syndrome 5	AR	N/A	N/A	Ophthalmologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15723066; 21220633; 23661368
IQSEC2	29059	23096	Mental retardation, X-linked 1	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7943039; 3177466; 20473311 
IRAK4	17967	51135	IRAK4 deficiency; Invasive pneumococcal disease, recurrent, isolated, 1	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	12637671; 15069404; 16647421; 17893200; 21734245 
IRF4	6119	3662	Skin/hair/eye pigmentation, variation in, 8	AD	N/A	N/A	Dermatologic	General		Though potentially related to melanoma susceptibility, the clinical relevance is unclear	17952075; 18483556; 19710684; 20602913; 24267888
IRF6	6121	3664	Popliteal pterygium syndrome; van der Woude syndrome; Orofacial cleft 6;	AD	N/A	N/A	Craniofacial; Dermatologic; Genitourinary; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Variants may additionally act as susceptibility factors (rather than being involved in Mendelian-inherited dominant disease)	13158329; 6573981; 2164325; 7628117; 10593995; 12219090; 14757865; 15317890; 16096995; 15558496; 17539900; 18247422; 18478600;  18836445; 20803643; 20799332; 21045959; 21082654; 21468557; 21739575; 21995291; 22488974; 24442519
IRF8	5358	3394	Immunodeficiency 32A (CD11C-positive/CD1C-positive dendritic cell deficiency); Immunodeficiency 32B (monocyte and dendritic cell deficiency)	AD	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals with Immunodeficiency 32A (CD11C-positive/CD1C-positive dendritic cell deficiency) have been described as demonstrating disseminated BCG disease that was amenable to treatment, and preventive measures, as well as prompt treatment of infection, may be beneficial; Individuals with Immunodeficiency 32B (monocyte and dendritic cell deficiency) demonstrate immunodeficiency, with severe opportunistic infections, and prophylactic  measures and prompt and aggressive treatment of infections may be beneficial; HSCT has been described	21524210
ISCU	29882	23479	Myopathy with lactic acidosis, hereditary	AR	Pediatric		Cardiovascular; Musculoskeletal; Renal	Musculoskeletal; Renal	Treatment (using an antisense phosphorodiamidate morpholino oligonucleotide) of cultured fibroblasts from three  individuals with a homozygous splice-site mutation resulted in restoration of the normal splicing pattern	In addition to cardiovascular features, the condition can include rhabdomyolysis, and appropriate precautions and prompt recognition may be beneficial	14213465; 5811159; 2384736; 18304497; 18296749; 19846308; 20206689
ISG15	4053	9636	Immunodeficiency 38	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may sufffer from severe infections (including Mycobacterial and Salmonella), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BCG vaccine has been reported as resulting in adverse reactions	22859821
ISPD	37276	729920	Muscular dystrophy-dystroglycanopathy (congenital, with brain and eye anomalies), type A, 7; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7	AR	N/A	N/A	Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7604843; 9492098; 22522421; 22522420; 23390185
ITCH	13890	83737	Autoimmune disease, syndromic multisystem	AR	Pediatric		Allergy/Immunology/Infectious; Craniofacial; Endocrine; Gastrointestinal; Neurologic; Pulmonary	Allergy/Immunology/Infectious; Endocrine		Individuals typically present with multisystem malformations, which may aid in clinical recognition, but awareness of disease may allow corticosteroid and other related immunosuppressive treatment related to autoimmune manifestations (including hypothyroidism, which responds to standard hormone replacement therapy), as well as awareness of the risk of frequent infections, which can allow prophylaxis/surveillance for infectious diseases, and early and aggressive treatment of infections	20170897
ITGA2B	6138	3674	Glanzmann thrombasthenia	AR	Pediatric		Hematologic	Hematologic		Individuals can have severe bleeding diatheses, and preventive measures as well as rapid treatment (which can include local measures as well as platelet transfusions, recombinant activated factor VII, and octreotide for GI bleeding) can be beneficial; Precipitating factors should be avoided	2014236; 8282784; 16463284; 19408193; 20020534; 21917754; 22102273; 21487445; 22250950; 22513797
ITGA3	6139	3675	Interstitial lung disease with nephrotic syndrome and epidermolysis bullosa	AR	N/A	N/A	Dermatologic; Pulmonary; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22512483
ITGA6	6142	3655	Epidermolysis bullosa, junctional, with pyloric stenosis	AR	N/A	N/A	Dermatologic; Gastrointestinal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9185503; 9158140; 11251584; 20301336 
ITGA7	6143	3679	Muscular dystrophy, congenital, due to integrin alpha-7 deficiency	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9590299; 19260934
ITGA8	6144	8516	Renal agenesis, bilateral	AR	N/A	N/A	Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24439109
ITGB2	6155	3689	Leukocyte adhesion deficiency, type I 	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals frequently first present with umbilical cord stump infection, and are prone to recurrent and severe bacterial infections, such that antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been described as effective	52003; 86829; 7310581; 7259263; 6718115; 6096477; 3703627; 2877234; 3510003; 2880869; 3234429; 3279017; 1972597; 7902162; 17244687; 19864007; 20351460; 20549317
ITGB3	6156	3690	Bleeding disorder, platelet-type, 16, autosomal dominant; Glanzmann thrombasthenia; Thrombocytopenia, neonatal alloimmune	AD/AR	Pediatric		Hematologic	Hematologic	Bi-allelic mutations have been described as resulting in a more severe phenotype; Specific variants may also be important in neonatal alloimune thrombocytopenia (as relates to platelet transfusions)	Individuals with dominant disease may demonstrate moderate to severe bleeding, and awareness may allow preventive measures and prompt management; Precipitating factors for bleeding episodes should be avoided (for both dominant and recessive disease forms); Individuals with bi-allelic mutations can have severe bleeding diatheses, and preventive measures as well as rapid treatment (which can include local measures as well as platelet transfusions, recombinant activated factor VII, and octreotide for GI bleeding) can be beneficial; Variants may be relevant to potential reactions from platelet transfusion, and knowledge may have relevance to related treatment	7193688; 2257303; 2428841; 2565345; 1967954; 2257303; 2392682; 2014236; 1371279; 1438206; 1602006; 1430225; 8093349; 8471765; 7694683; 8878424; 9160670; 9351872; 9845537; 9700201; 10583927; 10559451; 11425767; 11723016; 16721604; 16463284; 18065693; 19336737; 19408193; 20020534; 20081061; 20345392; 21917754; 22102273; 22250950; 22890234; 23146053; 23253071; 23929305
ITGB4	6158	3691	Epidermolysis bullosa, junctional, with pyloric atresia; Epidermolysis bullosa, junctional, non-Herlitz type; Epidermolysis bullosa simplex, Weber-Cockayne type 	AD/AR	N/A	N/A	Dermatologic; Gastrointestinal; Renal	Renal		In addition to gastrointestinal anomalies, the condition may include ureterovesical obstruction, and prompt recognition and treatment may be beneficial in terms of renal function	6177243; 7545057; 9674902; 9792864; 10484780; 10792571; 12485428; 18348258; 20301336; 20955205; 21969027; 22354727; 22674212 
ITK	6171	3702	Lymphoproliferative syndrome, EBV-associated, autosomal, 1	AR	Pediatric		Allergy/Immunology/Infectious; Oncologic	Allergy/Immunology/Infectious; Oncologic	Individuals may also have related predisposition to infectious complications	Due to the risk of malignancy, surveillance may allow prompt treatment; Medical treatment (eg, chemotherapy, virostatic agents, corticosteroids, rituximab) may induce remission, but treatment with HSCT may be required; Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	19425169; 21109689; 22289921; 22487848 
ITM2B	6174	9445	Cerebral amyloid angiopathy; Dementia, familial Danish; Retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities	AD	N/A	N/A	Audiologic/Otolaryngologic; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21610757; 7086452; 2364266; 10391242; 10781099; 11557758; 21048150; 24026677
ITPA	6176	3704	Inosine triphosphatase deficiency	AR	Pediatric		Biochemical	Pharmacogenomic		Abnormal 6-mercaptopurine metabolism in ITPase-deficient patients may cause thiopurine drug toxicity	1204209; 12384777; 17697198; 19214663; 19631656; 19682085 
ITPR1	6180	3708	Spinocerebellar ataxia 15; Spinocerebellar ataxia 29	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11445634; 11723290; 12828938; 14981189; 17030759; 17590087; 18579805; 17932120; 21555639; 21367767; 21827915; 22318346; 22986007 
IVD	6186	3712	Isovaleric acidemia	AR	Pediatric		Biochemical; Cardiovascular; Neurologic	Biochemical		Medical/dietary treatment (eg, with l-carnitine, glycine, and leucine restricted/low protein diet) can be effective; Specific measures can be taken to prevent severe sequelae of acute metabolic decompensation	5229850; 4378266; 4166104; 692626; 6630517; 3863140; 3139936; 3137519; 2063866; 15486829; 20142522; 20301313; 20662350; 20807522; 21207059; 21335445; 22004070; 22350545; 22960500; 23063737 
IYD	21071	389434	Thyroid dyshormonogenesis 4	AR	Pediatric		Endocrine	Endocrine	In heterozygotes, clinical hypothyroidism has been described as arising at a later age than in individuals with biallelic mutations	Individuals may present with clinical signs and sequelae of childhood hypothyroidism, which can lead to long-term neurologic and other effects, and medical  treatment of hypothyroidism (eg, with T4) can be beneficial 	18765512; 18434651; 22535972
JAG1	6188	182	Alagille syndrome	AD	Pediatric		Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic;  Ophthalmologic; Renal	Cardiovascular; Gastrointestinal; Renal	Mutations may be involved in other cardiac defects (such as Tetralogy of Fallot) in patients who do not overall meet clinical diagnostic criteria of Alagille syndrome;  Liver transplantation has been described	For hepatic complications, medications (eg, ursodeoxycholic acid, cholestyramine), and, when necessary, partial external biliary diversion may be beneficial; Other treatments, such as fat-soluble vitamin supplementation may be beneficial; Surveillance for other manifestations, including cardiac and renal manifestations, may be beneficial in order to allow early diagnosis and treatment and/or preventive measures; Contact sports should be avoided	803282; 9039994; 9207788; 9207787; 9585603; 9700188; 9890073; 10590916; 10213047; 11152664; 11313761; 11511567; 11139239; 12244552; 12239725; 12509572; 14993126; 16013021; 16573599;  17286312; 19597493; 19948535; 20301450; 20437614; 22040217; 22105858; 22488849; 22521120; 22759690; 22937766; 23752887; 23801938; 23956173
JAGN1	26926	84522	Neutropenia, severe congenital, 6	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may sufffer from severe, recurrent bacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported	25129144
JAK2	6192	3717	Thrombocythemia 3	AD	Adult	Variants may be involved in predisposition to and pathogenesis of oncologic processes (AD)	Hematologic	Hematologic		Individuals may be at high risk of thrombosis, and preventive measures and early treatment of manifestations may be beneficial	16762626; 16707754; 17989398; 19036091; 19287384; 19287385; 19338077; 19847199; 22397670; 22696908; 22571758 
JAK3	6193	3718	Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, natural killer cell-negative 	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported as effective for T-cell reconstitution, but less succesful as relates to B and NK-cell function	7659163; 7481768; 14615376; 21184155; 21732012; 23001410
JAM3	15532	83700	Hemorrhagic destruction of the brain, subependymal calcification, and cataracts	AR	N/A	N/A	Cardiovascular; Neurologic; Ophthalmologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21109224; 23255084
JPH2	14202	57158	Cardiomyopathy, familial hypertrophic 17	AD	Pediatric		Cardiovascular	Cardiovascular		Surveillance and preventive measures, including medical management, may reduce morbidity 	17476457; 17509612; 22515980 
JPH3	14203	57338	Huntington disease-like 2	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11694876; 11761463; 11914418; 11940688; 12805114; 14557581; 18816802; 19735092; 22367996; 22971727
JUP	6207	3728	Arrhythmogenic right ventricular dysplasia, familial, 12; Naxos disease	AD/AR	Adult		Cardiovascular; Dermatologic	Cardiovascular	Dermatologic findings may be apparent in Naxos disease, but cardiac association may not be readily appreciated	Individuals may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation 	2945574; 10902626; 17924338; 20301310; 22527912
KAL1	6211	3730	Kallmann syndrome 1	XL/Digenic	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Dental; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Renal	Audiologic/Otolaryngologic; Endocrine	Digenic inheritance (with PROKR2) has been reported	Surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to  fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required; As the condition may include hearing loss, recognition and interventions related to speech and language development may be beneficial	6772660; 3312278; 3101500;  8504298; 7677154; 8989261; 9713559; 10944855; 11297579; 15001591; 8768867; 16882753; 8160472; 20301509; 20949504; 23533228
KANK1	19309	23189	Cerebral palsy, spastic quadriplegic, 2	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16301218
KANK2	29300	25959	Palmoplantar keratoderma and woolly hair	AR	N/A	N/A	Dermatologic; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11874502; 24671081
KANSL1	24565	284058	Koolen-de Vries syndrom	AD	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22482802; 22544363
KARS	6215	3735	Charcot-Marie-Tooth disease, recessive intermediate B	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20920668
KAT6B	17582	23522	Ohdo syndrome, SBBYS variant; Genitopatellar syndrome	AD	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Dental; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Audiologic/Otolaryngologic; Endocrine	The conditions can involve multiple congenital anomalies	Among other manifestations, individuals may demonstrate early-onset hypothyroidism, and appropriate management may be beneficial; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	12210329; 12210330; 12949978; 16761293; 21412151; 22077973; 22265014; 23236640
KBTBD13	37227	390594	Nemaline myopathy 6	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11731279; 21104864; 21109227
KCNA1	6218	3736	Episodic ataxia, type 1/myokymia syndrome	AD	Pediatric		Neurologic; Renal	Renal	For episodic ataxia medical treatment (eg, with phenytoin) may be effective, but the benefit of an early (genetic) diagnosis is unclear	Individuals can have severe hypomagnesemia, which is responsive to magnesium therapy	7842011; 11026449; 17136396; 19307729
KCNA5	6224	3741	Atrial fibrillation, familial, 7	AD	Adult		Cardiovascular	Cardiovascular		Surveillance for and medical intervention to prevent morbidity related to atrial fibrillation may be beneficial	16772329; 17266934; 19343045; 20638934 
KCNC3	6235	3748	Spinocerebellar ataxia 13	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16501573
KCND3	6239	3752	Spinocerebellar ataxia 19; Spinocerebellar ataxia 22	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23280837; 23280838
KCNE1	6240	3753	Long QT syndrome 5; Jervell and Lange-Nielsen syndrome 2	AD/AR/Digenic	Pediatric		Audiologic/Otolaryngologic; Cardiovascular	Audiologic/Otolaryngologic; Cardiovascular	Heterozygous mutations cause long QT-syndrome 1 (Ward Romano syndrome); Biallelic mutations cause Jervell and Lang-Nielsen syndrome, which includes congenital deafness; Digenic/complex inheritance has been reported	Preventive measures and medical management may be helpful to help decrease morbidity related to long-QT syndrome; In JLNS, treatment of deafness may also be beneficial for language and related development	13435203; 6991948; 9354802; 9328483; 10973849; 15051636; 14760488; 15840476; 16922724; 20301308; 20301579; 20809527; 21070882 
KCNE2	6242	9992	Long QT syndrome 6; Atrial fibrillation, familial 4	AD	Pediatric		Cardiovascular	Cardiovascular; Pharmacogenomic	Digenic/complex inheritance has been reported	In Long QT syndrome, in order to prevent sequelae including syncope, cardiac arrest and sudden death prophylactic use of beta blockers in asymptomatic individuals may be beneficial; ICD may be indicated for individuals refractory to beta-blocker treatment or  with history of cardiac arrest; Agents that can contribute to prolonged QT or related dysrhythmias should be avoided, as should activities associated with high stress/intense exertion; In Atrial fibrillation, surveillance and risk awareness can allow early detection and medical treatment of disease, including related sequelae (eg, thromboembolic events)	10219239; 10973849; 15368194; 15840476; 16922724; 20301308; 20809527 
KCNE3	6243	10008	Brugada syndrome 6	AD	Pediatric		Cardiovascular	Cardiovascular; Pharmacogenomic		Surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial;  Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever	12414843; 14504341; 15037716; 15212652; 19122847; 19306396; 19606473; 20301690; 22397033; 22987075 
KCNH2	6251	3757	Long QT syndrome 2; Short QT syndrome 1	AD	Pediatric		Cardiovascular	Cardiovascular	Digenic/complex inheritance has been reported	In Long QT syndrome, medical/surgical management (eg, with beta-blockers or ICD placement) may help prevent/decrease severe sequelae; Activities (eg, stress, certain types of physical activity) or agents (eg, certain medications) that contribute to further QT interval prolongation should be avoided; In Short QT syndrome, medical/surgical management (eg, with antiarrhythmics or ICD placement) may help prevent/decrease severe sequelae	9753711; 9694858; 9927398; 9950666; 11173780; 12925462; 14676148; 15280551; 16132053; 15828882; 15890322; 15840476; 11854117; 16075043; 16922724; 19926013; 20301308; 20809527; 21070882; 21130771; 21440677; 22382559; 22821100; 22882672; 23010577; 23098067 
KCNJ1	6255	3758	Bartter syndrome, antenatal, type 2	AR	Pediatric (and prenatal)		Renal	Renal		Prenatal therapy has been reported as being beneficial; In infants, specific medications (eg, COX2 inhibitors) have been reported as beneficial; Correction of hypokalemic alkalosis can be beneficial	841184; 9002665; 10049979; 10979805
KCNJ10	6256	3766	Enlarged vestibular aqueduct, digenic; Pendred syndrome, digenic; Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SESAME syndrome)	AR/Digenic	Pediatric		Audiologic/Otolaryngologic; Neurologic; Renal	Audiologic/Otolaryngologic; Renal	Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalances manifests with deafness, as well as electrolyte abnormalities; Digenic inheritance has been reported	Individuals with Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalances display early-onset electrolyte abnormalities (eg, hypokalemia, metabolic alkalosis, and hypomagnesemia due to renal salt wasting), and treatment related to electrolyte imbalances may be beneficial; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	19420365; 19289823; 19289823; 19426954; 21849804
KCNJ11	6257	3767	Hyperinsulinemic hypoglycemia, familial, 2; Diabetes mellitus, transient neonatal, 3; Diabetes, permanent neonatal; Diabetes, permanent neonatal, with Neurologic features	AD/AR	Pediatric	Paternally-inherited mutations can cause Focal adenomatous hyperplasia (AD)	Endocrine; Neurologic	Endocrine		Individuals may manifest in infancy with findings including intrauterine growth retardation, postnatal growth deficiency, and signs of diabetes mellitus (eg, hyperglycemia, glycosuria), as well as severe dehydration, and recognition can allow preventive measures related to potential sequelae, surveillance (eg, with blood glucose monitoring as well as surveillance for other common sequelae of diabetes mellitus affecting systems such as the renal and ophthalmogic systems); In the case of an acute diabetic crisis, rapid treatment (eg, with rehydration and IV insulin, transitioning to SQ insulin when stable) is indicated, though rapid-acting and (non-continuous) short-acting insulin preparations may result in severe hypoglycemia in young patients; Individuals with neonatal diabetes mellitus due to KCNJ11 mutations may specifically respond well to oral sulfonylurea treatment 	8923010; 9356020; 11395395; 15115830; 15579781; 15531505; 15562009; 15718250; 15998776; 15784703; 16731833; 16885550; 17327377; 17213273; 18556340; 18596924; 19357197; 20022885; 20049716; 20301620; 20546268 
KCNJ13	6259	3769	Snowflake vitreoretinal degeneration; Leber congenital amaurosis 16	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4812083; 15557460; 18179896; 18309337; 21763485
KCNJ18	39080	100134444	Thyrotoxic periodic paralysis, susceptibility to	AD	Pediatric		Endocrine	Endocrine		Treatment of underlying hyperthyroidism is an effective treatment	16608889; 20074522; 21665951 
KCNJ2	6263	3759	Atrial fibrillation, familial 9; Short QT syndrome 3; Andersen syndrome; Long QT syndrome 7	AD	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular		Depending on the cardiac phenotype, specific medical intervention to prevent morbidity and mortality related to arrhythmias can be beneficial; Surveillance for cardiac events is indicated	4106724; 5007210; 8080508; 9307251; 10406668; 11371347; 12148092; 12177393; 12086641; 12163457; 12796536; 15761194; 15890322; 16217063; 15922306; 16571646; 16419128; 16769944; 17324964; 17211524; 19931173; 20111058; 20301441; 20382953; 20809527; 21148745; 21493816; 21875779; 22155372; 22589293 
KCNJ5	6266	3762	Long QT syndrome 13; Hyperaldosteronism, familial, type III	AD	Pediatric		Cardiovascular; Endocrine	Cardiovascular; Endocrine		In Long QT syndrome, preventive measures and medical management may be helpful to help decrease morbidity; sudden death in infancy has been reported; In Hyperaldosteronism, familial, hypertension and aldosteronism are not reversed by administration of exogenous glucocorticoids and patients require adrenalectomy 	18505761; 20301308; 20560207; 21311022; 22447138; 22628607; 24574546
KCNK3	6278	3777	Pulmonary artery hypertension, familial	AD	Pediatric		Cardiovascular; Pulmonary	Cardiovascular; Pulmonary		While prognosis is overall poor, medical therapy  may be beneficial, though heart/lung transplantation may be required; Control of complications may be beneficial	23883380
KCNK9	6283	51305	Birk-Barel mental retardation dysmorphism syndrome	AD	N/A	N/A	Craniofacial; Dental; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18678320
KCNMA1	6284	3778	Generalized epilepsy and paroxysmal dyskinesia	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15937479
KCNQ1	6294	3784	Long QT syndrome 1; Jervell and Lange-Nielsen syndrome 1; Short QT syndrome 2; Atrial fibrillation, familial 3	AD/AR/Digenic	Pediatric		Audiologic/Otolaryngologic; Cardiovascular	Audiologic/Otolaryngologic; Cardiovascular	The age of onset of clinical manifestations may be highly variable; The condition can manifest with hearing loss in JLNS1 in addition to cardiac manifestations; Digenic inheritance (eg, with KCNH2) has been described	Medical/surgicalmanagement  (eg, ICD placement, antiarhythymognic medications) may help prevent/decrease severe sequelae, though cardiac transplantion has been necessary for some individuals; For individuals with JLNS1, recognition and prompt treatment of hearing loss may be beneficial	13435203; 4393533; 112730; 7365362; 6991948; 7471361; 1884444; 8892796; 8872472; 8528244; 9020846; 9164812; 9702906; 9593563; 9753711; 10086971; 10077519; 10220144; 10973849; 11140949; 11289718; 11479253; 11433047; 12522251; 12736279; 15159330; 15051636; 16132053; 15890322; 15840476; 16461811; 16922724; 18580685; 19261104; 20301308; 20301579; 21185499; 21952006; 22293141; 22456477; 22708720; 22727609; 22882672; 22885918; 23000022 
KCNQ2	6296	3785	Epileptic encephalopathy, early infantile, 7; Benign familial neonatal seizures, 1; Myokymia	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7980108; 9430594; 9425895; 11572947; 12742592; 15249611; 16235065; 16966552; 17675531; 17872363; 19822871; 22169383; 22275249; 22884718; 22926866 
KCNQ3	6297	3786	Seizures, benign neonatal, 2	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1859177; 8102508; 9425900; 20437616; 22612257 
KCNQ4	6298	9132	Deafness, autosomal dominant 2A	AD	N/A	N/A	Audiologic/Otolaryngologic	General	The onset of deafness appears postlingual	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10369879; 10025409; 16596322; 18030493; 23399560; 23443030; 23451214; 23717403
KCNT1	18865	57582	Epilepsy, nocturnal frontal lobe, 5; Early infantile epileptic encephalopathy 14	AD	N/A	N/A	Neurologic	General	As with other forms of epilepsy, optimal seizure control is advantageous	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing	18479385; 23086396; 23086397; 23599387
KCNV2	19698	169522	Retinal cone dystrophy 3B	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16909397
KCTD7	21957	154881	Epilepsy, progressive myoclonic 3	AR	N/A	N/A	Neurologic	General	As with other forms of epilepsy, optimal seizure control is advantageous	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing	17455289; 22606975; 22638565; 22693283; 22748208
KDM5C	11114	8242	Mental retardation, X-linked, syndromic, Claes-Jensen type	XL	N/A	N/A	Craniofacial; Genitourinary; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10982473; 15586325; 16538222; 18697827; 18203167; 19826449; 21575681; 22326837; 22611640 
KDM6A	12637	7403	Kabuki syndrome 2	XL	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22197486; 23076834
KEL	6308	3792	Blood group, Kell system	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	7849312; 11134029; 12842980; 15373667; 16423827
KERA	6309	11081	Cornea plana congenita, recessive	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10802664; 11726611; 15370545; 17679937 
KHDC3L	33699	154288	Hydatidiform mole, recurrent, 2	AR	Pediatric		Obstetric; Oncologic	Obstetric; Oncologic		Women are likely to have pregnancies with hydatidiform moles, with a high risk of persistent trophoblastic disease, including requiring  chemotherapeutic treatment, and awareness may allow reproductive planning and/or surveillance measures, which may allow early detection and treatment	11932746; 19246479; 21623199; 21885028
KHK	6315	3795	Fructosuria, essential	AR	N/A	N/A	Biochemical	General		The clinical relevance is unclear	13759156; 14063525; 6268573; 7816517; 7833921
KIAA0196	28984	9897	Spastic paraplegia 8; Ritscher-Schinzel syndrome (3C syndrome)	AD/AR	N/A	N/A	Neurologic	General	Ritscher-Schinzel syndrome (3C syndrome) may involve multiple congenital anomalies, including cardiovascular malformations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7604842; 10797436; 17160902; 20301727; 23455931; 24065355
KIAA0226	28991	9711	Spinocerebellar ataxia 15	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20826435; 23728897
KIAA1033	29174	23325	Mental retardation, autosomal recessive 43	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21498477
KIAA1279	23419	26128	Goldberg-Shprintzen megacolon syndrome	AR	N/A	N/A	Gastrointestinal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7338549; 10874640; 15883926
KIAA2022	29433	340533	Mental retardation, X-linked 98	XL	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15466006; 23615299
KIF11	6388	3832	Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation, autosomal dominant	AD	N/A	N/A	Cardiovascular; Craniofacial; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15930898; 22653704; 22284827
KIF1A	888	547	Mental retardation, autosomal dominant 9; Neuropathy, hereditary sensory, type IIC; Spastic paraplegia 30, autosomal recessive	AD/AR	N/A	N/A	Neurologic	General	Insensitivity to pain can result in injuries and infections	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21376300; 21487076; 21820098; 22258533 
KIF1B	16636	23095	Neuroblastoma, susceptibility to; Pheochromocytoma	AD	Pediatric	Allelic with Charcot-Marie-Tooth disease, type 2A1 (AD)	Neurologic; Oncologic	Oncologic		Surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality	9409358; 11389829; 18334619; 24102379
KIF1C	6317	10749	Spastic ataxia 2, autosomal recessive	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24319291; 24482476
KIF21A	19349	55605	Fibrosis of extraocular muscles, congenital 1; Fibrosis of extraocular muscles, congenital 3B	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10922204; 14595441; 15621877; 15621876; 15223798; 15671279; 15827546; 18332320; 19896199; 20301522; 21042561; 21805025 
KIF22	6391	3835	Spondyloepimetaphyseal dysplasia with joint laxity, type 2	AD	N/A	N/A	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19277648; 22152677
KIF2A	6318	3796	Cortical dysplasia, complex, with other brain malformations 3	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23603762
KIF4A	13339	24137	Mental retardation, X-linked 100	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24812067
KIF5A	6323	3798	Spastic paraplegia 10, autosomal dominant	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10441583; 12355402; 15452312; 16489470; 16476820; 18245137; 18853458; 21107874; 21623771; 22788249; 25008398
KIF5C	6325	3800	Cortical dysplasia, complex, with other brain malformations 2	AD	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23033978; 23603762; 24812067
KIF7	30497	374654	Hydrolethalus syndrome 2; Acrocallosal syndrome; Joubert syndrome 12	AR/Digenic	N/A	N/A	Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Renal; Ophthalmologic	General	The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Digenic inheritance (with CEP41) has been reported	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	457430; 7424976; 7102724; 7166318; 3802558; 3366141; 2658584; 2729349; 2729348; 2658583; 2308155; 2051463; 1659985; 1887856; 1499582; 8092201; 8723075; 11857542; 18618999; 20301500; 21633164; 21552264; 22246503; 22587682; 23142271 
KIRREL3	23204	84623	Mental retardation, autosomal dominant 4	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19012874
KISS1	6341	3814	Hypogonadotropic hypogonadism 13 with or without anosmia	AR	Pediatric		Endocrine; Neurologic	Endocrine		In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	20301509; 22335740
KISS1R	4510	84634	Hypogonadotropic hypogonadism 8 with or without anosmia	AR	Pediatric	Allelic with Precocious puberty, central (AD/AR)	Endocrine; Neurologic	Endocrine	In Precocious puberty, treatment with gonadotropin-releasing hormone receptor analogs/LHRH agonists can be beneficial	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	11600530; 12788910; 12788881; 14573733; 18272894; 20301509
KIT	6342	3815	Gastrointestinal stromal tumor	AD	Adult		Oncologic	Oncologic		Surveillance may allow early diagnosis and treatment of gastrointestinal stromal tumors (including with tyrosine kinase inhibitors such as imatinib), which may improve outcomes	9697690; 11073817; 11505412; 16143141; 16185297; 17824795; 18724244; 18183595; 19847891; 22083669 
KITLG	6343	4254	Hyperpigmentation, familial progressive 2; Skin/hair/eye pigmentation, variation in, 7	AD	N/A	N/A	Dermatologic	General		The condition may not be clinically relevant; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18083106; 17952075; 19375057
KIZ	15865	55857	Retinitis pigmentosa 69	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24680887
KL	6344	9365	Tumoral calcinosis, hyperphosphatemic	AR	Pediatric		Dermatologic; Musculoskeletal; Renal	Renal		Phosphate reduction (eg, with dietary means and phosphate-binding agents) can be beneficial	4538804; 3659264; 2777854; 12541190; 17710231
KLF1	6345	10661	Anemia, dyserythropoietic congenital, type IV; Blood group, Lutheran inhibitor	AD/BG	Pediatric	Allelic with Hereditary persistence of fetal hemoglobin (AD) (the described proband presented with mild hypochromic, microcytic red cell indices, but no other phenotypic abnormalities were reported)	Hematologic	Hematologic	One individual has been described with multiple congenital anomalies in addition to hematologic perturbations	Treatments (including regular RBC transfusions and splenectomy) may be beneficial; Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	1659863; 7680924; 7521883; 17319831; 18487511; 21055716; 20676099; 21531944; 21821711; 21273267; 22093801; 22102705
KLF11	11811	8462	Maturity-onset diabetes of the young, type VII	AD	N/A	N/A	Endocrine	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15774581
KLHDC8B	28557	200942	Hodgkin lymphoma	AD	Pediatric		Oncologic	Oncologic	One family with a gene disruption has been described	Surveillance and/or awareness of cancer risk may allow early diagnosis, which could potentially be beneficial	19706467
KLHL10	18829	317719	Spermatogenic failure 11	AD	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17047026
KLHL3	6354	26249	Pseudohypoaldosteronism, type IID	AD/AR	Pediatric		Renal	Renal		Treatment (eg, correction of physiologic abnormalities by thiazide diuretics) can be effective	22266938
KLHL40	30372	131377	Nemaline myopathy 8	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23746549
KLHL41	16905	10324	Nemaline myopathy 9	AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24268659
KLHL7	15646	55975	Retinitis pigmentosa 42	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1872134; 19520207; 20547956; 22084217
KLK4	6365	9622	Amelogenesis imperfecta, type IIA1	AR	N/A	N/A	Dental	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15235027; 23355523 
KLKB1	6371	3818	Prekallikrein deficiency	AR	N/A	N/A	Hematologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5845778; 5420590; 694428; 6568197; 3487556; 7717377; 6918357; 15461630; 19404525 
KLLN	37212	100144748	Cowden syndrome 4 	AD	Adult		Dermatologic; Oncologic	Oncologic	Germline hypermethylation and epigenetic inactivation of the KLLN promoter has been described in affected individuals	Individuals have been reported with a high risk of breast and renal cancer, and surveillance may allow early diagnosis and management of neoplastic processes	21177507; 21956414 
KMT2A	7132	4297	Wiedemann-Steiner syndrome	AD	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22795537
KMT2D	7133	8085	Kabuki syndrome 	AD	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dental; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Cardiovascular; Renal		Congenital heart defects, as well as arrhythmias, are frequent in affected individuals, and surveillance may allow early diagnosis and treatment; Individuals may have renal anomalies and/or vesicoureteral reflux, and screening for renal anomalies (eg, with ultrasound and functional testing) may allow measures to help monitor and preserve renal function	3067577; 8048822; 10190924; 11343317; 11665999; 12002156; 15108197; 15887282; 20711175; 21671394; 21607748; 21882399; 22126750; 23535010 
KNG1	6383	3827	High molecular weight kininogen deficiency	AR	N/A	N/A	Hematologic	General	Most individuals are asymptomatic, though one individual has been reported with cerebral artery thrombosis after moderate trauma	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1202089; 1174709; 16695963; 48123; 127805; 3728458; 1968772; 7901207; 12576314
KPTN	6404	11133	Mental retardation, autosomal recessive 41	AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24239382
KRAS	6407	3845	Noonan syndrome; Cardiofaciocutaneous syndrome	AD	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic	Cardiovascular; Hematologic; Oncologic		Surveillance and treatment related to manifestations such as cardiac anomalies (which can include hypertrophic cardiomyopathy and arrhythmias) and short stature can be beneficial; An individual has been reported with a hematologic malignancy, and surveillance may be beneficial; Precautions related to bleeding risk can be beneficial	16474405; 16474404; 16474405; 17468812; 17056636; 18456719; 18042262; 19396835; 20301303; 20301365; 20358587; 20602484; 20876176; 21797849; 22211815; 22777296; 22510777; 23885229
KRIT1	1573	889	Cerebral cavernous malformations 1	AD	Pediatric		Cardiovascular; Dermatologic; Neurologic	Cardiovascular; Neurologic; Pharmacogenomic		Surveillance measures (eg, spinal cord MRI, annual brain gradient echo or susceptibility-weighted imaging) has been advocated; Agents that increase risk of hemorrhage should be avoided (eg, aspirin, NSAIDs, heparin, warfarin). 	10508515; 10545614; 10814716; 11222804; 11310633; 11161805; 12404106; 11831930; 11914398; 15079030; 17562932; 17211633; 18060436; 18207546; 19099113; 19453802; 19454328; 20301470; 20306072; 20646827; 20689144; 20884211; 21029238; 22261708; 22510019; 22699465; 23584803; 23663874; 23806994; 23828392; 24007869; 24058906
KRT1	6412	3848	Keratosis palmoplantaris striata III; Ichthyosis, cyclic, with epidermolytic hyperkeratosis; Ichthyosis histrix, Curth-Macklin type; Palmoplantar keratoderma, epidermolytic; Palmoplantar keratoderma, nonepidermolytic; Epidermolytic hyperkeratosis	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14349943; 1381288; 1380725; 7682695; 7528239; 7512983; 10053007; 11286630; 11286616; 12406346; 11982762; 12648226; 16361731; 16417221; 16439967; 16487115; 16677804; 17255957; 18795921; 19470048; 21271994; 21496707; 22250628; 22834809 
KRT10	6413	3858	Erythroderma, ichthyosiform, congenital reticular; Aaru disease; Ichthyosis, cyclic, with epidermolytic hyperkeratosis; Epidermolytic hyperkeratosis 	AD/AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1381287; 1380725; 7682695; 9036939; 19443303; 19474805; 19689541; 20302579; 20798280; 21271994; 21463361; 21929535; 22035476 
KRT12	6414	3859	Meesmann corneal dystrophy	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9171831; 18661274; 20577595 
KRT13	6415	3860	White sponge nevus 2	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7493031
KRT14	6416	3861	Epidermolysis bullosa simplex, autosomal recessive; Naegeli-Franceschetti-Jadassohn syndrome; Dermatopathia pigmentosa reticularis; Epidermolysis bullosa simplex, Koebner type; Epidermolysis bullosa simplex, Weber-Cockayne type; Epidermolysis bullosa simplex, Dowling-Meara type; Naegeli-Franceschetti-Jadassohn syndrome	AD/AR	N/A	N/A	Dental; Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13149726; 939040; 1717157; 1303619; 7506606; 7526933; 7682883; 8496458; 7682695; 7525408; 7525407; 16098032; 16960809; 20180888; 20199538; 20301543; 21375516; 21593775; 21623745; 21818518; 21967011 
KRT16	6423	3868	Palmoplantar keratoderma, nonepidermolytic, focal; Pachyonychia congenita 1	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7544664; 8595410; 10521820; 10839714; 11359398; 11886499; 20301457; 21160496; 21326300; 22098151; 22668561 
KRT17	6427	3872	Steatocystoma multiplex; Pachyonychia congenita 2	AD	N/A	N/A	Dental; Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7529318; 7539673; 9008238; 11886499; 20301457; 22264670 
KRT2	6439	3849	Ichthyosis bullosa of Siemens; Ichthyosis exfoliativa	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2138447; 2004005; 8077693; 7524919; 7521372; 9833038; 10084318; 10233323; 10620137; 11167982; 15949009 
KRT3	6440	3850	Meesmann corneal dystrophy	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9171831
KRT4	6441	3851	White sponge nevus 1	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7493030; 10652003; 12828738
KRT5	6442	3852	Epidermolysis bullosa simplex with migratory circinate erythema; Epidermolysis bullosa simplex with mottled pigmentation; Dowling-Degos disease 1; Epidermolysis bullosa simplex, Koebner type; Epidermolysis bullosa simplex, Weber-Cockayne type; Epidermolysis bullosa simplex, Dowling-Meara type	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19991630; 13171638; 3188604; 1718160; 1372711; 7688477; 7686424; 7682695; 7520042; 7537780; 7534039; 8799157; 9129237; 10234505; 10730767; 11167681; 11407989; 12925204; 15324323; 16098032; 16465624; 20923750; 21144712 ; 21375516; 21569119; 22005030; 22583733; 22639907; 22747925 
KRT6A	6443	3853	Pachyonychia congenita 3	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7545493; 11886499; 20301457; 22098151; 22264670; 22668561 
KRT6B	6444	3854	Pachyonychia congenita 4	AD	N/A	N/A	Dental; Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9618173; 11886499; 20301457 
KRT6C	20406	286887	Palmoplantar keratoderma, nonepidermolytic, focal or diffuse	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19609311; 21801157; 23662636
KRT71	28927	112802	Hypotrichosis 13	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22592156
KRT74	28929	121391	Ectodermal dysplasia 7, hair/nail type; Hypotrichosis 3; Woolly hair, autosomal dominant	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20346438; 20409997; 21188418; 24714551
KRT75	24431	9119	Pseudofolliculitis barbae	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15086549
KRT81	6458	3887	Monilethrix	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9665406; 15744029; 22628999 
KRT83	6460	3889	Monilethrix	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15744029
KRT85	6462	3891	Ectodermal dysplasia 4, hair-nail type	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16525032; 19865094
KRT86	6463	3892	Monilethrix	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9241275; 9665406,; 10878478; 15744029; 19400537; 22568869; 22670615 
KRT9	6447	3857	Palmoplantar keratoderma, epidermolytic; Knuckle pads	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7528239; 7512862; 7511021; 9856842; 12192490; 12838553; 17074468; 19106041
KYNU	6469	8942	Hydroxykynureninuria	AR	N/A	N/A	Biochemical	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17334708
L1CAM	6470	3897	Hydrocephalus due to congenital stenosis of aqueduct of Sylvius; Mental retardation, aphasia, shuffling gait, and adducted thumbs (MASA) syndrome; CRASH syndrome; Corpus callosum, partial agenesis of; Spastic paraplegia-1	XL	N/A	N/A	Gastrointestinal; Musculoskeletal; Neurologic	General	Individuals may be at risk for findings including Hirschsprung disease as well as hydrocephalus	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4855169; 7070456; 6702900; 2737668; 2277384; 1870106; 1303258; 7920659; 8062435; 7920660; 8556302; 7562969; 9279760; 15368500; 16650080; 21271669; 21644943; 21839187; 21961551; 22222883; 22344793; 22354677 
L2HGDH	20499	79944	L-2-hydroxyglutaric aciduria	AR	Pediatric		Biochemical; Neurologic; Oncologic	Biochemical; Oncologic		A low lysine diet has been reported as resulting in clinical and biochemical improvement; An increased risk of cerebral neoplasms has been reported, and awareness may lead to early detection and treatment	6787330; 1642474; 7609438; 7609437; 9860123; 10399870; 15548604; 15385440; 15824270; 18931888; 21937992; 22241392; 22353300; 22459673
LAMA1	6481	284217	Poretti-Boltshauser syndrome	AR	N/A	N/A	Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	25105227
LAMA2	6482	3908	Muscular dystrophy, congenital merosin-deficient, 1A; Schizophrenia	AD/AR	N/A	N/A	Musculoskeletal; Neurologic	General	Clinically significant cardiomyopathy has not been described	In Muscular dystrophy, congenital merosin-deficient, 1A, Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; In Schizophrenia, the evidence or clinical applicability is unclear	7550355; 8887959; 8729391; 12552556; 16216942; 18700894; 20627570; 21953594; 22166137; 22675738; 23042115 
LAMA3	6483	3909	Laryngoonychocutaneous syndrome; Epidermolysis bullosa, junctional, Herlitz type; Epidermolysis bullosa, generalized atrophic benign 	AR	N/A	N/A	Audiologic/Otolaryngologic; Dental; Dermatologic 	General	The condition can include life-threatening respiratory obstruction	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1342856; 8185366; 7633458; 8530087; 8618022; 8586427; 11810295; 12915477; 20301304; 20881434; 22434185; 22963541 
LAMA4	6484	3910	Cardiomyopathy, dilated, 1JJ	AD	Pediatric		Cardiovascular	Cardiovascular	Although clinical effects have been described in older individuals, in at least one individual, the onset of cardiac pathology was such that surveillance may be indicated prior to adulthood	Individuals may have cardiovascular manifestations including dilated cardiomyopathy, and surveillance (eg, with echocardiogram) may allow detection and early medical treatment, which may be beneficial to help decrease morbidity; Heart transplantation was described as indicated in one individual	17646580
LAMB1	6486	3912	Lissencephaly 5	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23472759
LAMB2	6487	3913	Pierson syndrome; Nephrotic syndrome, type 5, with or without ocular abnormalities	AR	N/A	N/A	Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Chronic renal dialysis can extend life of affected individuals	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14136829; 15367484; 16912710; 17256789; 19251977; 21236492
LAMB3	6490	3914	Epidermolysis bullosa, junctional, Herlitz type; Epidermolysis bullosa, junctional, non-Herlitz type 	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7706760; 7774918; 9205497; 9242513; 11023379; 15538630; 16473856; 17476356; 20301304; 19369679; 20301304; 21801158 
LAMC2	6493	3918	Epidermolysis bullosa, junctional, Herlitz type; Epidermolysis bullosa, junctional, non-Herlitz type 	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8012393; 11810295; 16473856; 21198797; 21801158 
LAMC3	6494	10319	Cortical malformations, occipital	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21572413
LAMP2	6501	3920	Danon disease	XL	Pediatric		Biochemical; Cardiovascular; Musculoskeletal; Neurologic	Cardiovascular	Males typically display mental retardation and other recognizable features, but females may be affected with cardiomyopathy and arrhthymias	Surveillance (eg, with EKG and electrocardiogram) and medical management can help decrease morbidity related to cardiomyopathy and arrhythmias; Heart transplant has been suggested to be the only truly effective treatment	6450334; 3806120; 3057987; 8504498; 7919972; 10972294; 12084876; 15253947; 15673802; 15889279; 15792868; 15907287; 17899313; 19318653; 21161685; 21816855; 22074992; 22365987; 22541782; 22750798 
LAMTOR2	29796	28956	Immunodeficiency due to defect in MAPBP-interacting protein	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Musculoskeletal	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial (severe congenital neutropenia has been reported as responding to G-CSF) 	17195838
LARGE	6511	9215	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6 	AR	N/A	N/A	Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12966029; 17878207; 17436019; 19067344; 19299310; 21248746
LARP7	24912	51574	Alazami syndrome	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22865833
LARS	6512	51520	Liver failure, infantile, syndromic	AR	N/A	N/A	Gastrointestinal; Hematologic; Neurologic; Renal	General	Only one family has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22607940
LARS2	17095	23395	Perrault syndrome 4	AR	Pediatric		Audiologic/Otolaryngologic; Endocrine; Obstetric	Obstetric		Genetic knowledge may allow fertility preservation such as by storing eggs in woman with premature ovarian failure	23541342
LBR	6518	3930	Hydrops-ectopic calcification-moth-eaten skeletal dysplasia; Reynolds syndrome; Pelger-Huet anomaly; Greenberg/HEM skeletal dysplasia	AD	N/A	N/A	Craniofacial; Hematologic; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5553949; 3475111; 12118250; 14684694; 12618959; 20522425; 22338047 
LCA5	31923	167691	Leber congenital amaurosis 5	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10631161; 12642313; 17546029; 18334959; 20301475; 21850168 
LCAT	6522	3931	Lecithin:cholesterol acyltransferase deficiency; Fish-eye disease	AR	Pediatric		Biochemical; Cardiovascular; Hematologic; Ophthalmologic; Renal	Cardiovascular; Renal		Dietary measures (eg, reducing fat intake) may be beneficial in controlling LDL and decreasing sequelae; In LCAT deficiency, medical treatment related to renal disease (eg, with ACE inhibitors) may preserve renal function, though renal transplant may be required 	5704704; 408950; 7156322; 7148518; 6624548; 6695915; 3661502; 1898657; 2370048; 2052566; 9180249; 9884427; 18042612; 21901787; 22108153; 22189200; 22701329; 23043194; 23391322; 23412821; 23522979
LCK	6524	3932	Immunodeficiency 22	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	9664084; 11351273; 22985903
LCT	6530	3938	Lactase deficiency, congenital	AR	Pediatric		Gastrointestinal	Gastrointestinal	Upstream/noncoding variants may also result in adult-onset lactose intolerance	Breast-feeding or lactose-containing formulas leads to severe osmotic diarrhea, which can be treated effectively with lactose-free diet	5419986; 6847226; 9758622; 11788828; 16400612; 17345962; 19161632; 19432082; 22688420; 23445879
LDB3	15710	11155	Cardiomyopathy, dilated 1C; Left ventricular noncompaction 3, with or without dilated cardiomyopathy; Myopathy, myofibrillar 4	AD	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular	LVNC may present early, while other cardiac manifestations may not present until much later	Individuals may have cardiovascular manifestations including dilated cardiomyopathy, and surveillance (eg, with echocardiogram) may allow detection and early medical treatment, which may be beneficial to help decrease morbidity; In myofibrillar myopathy, individuals typically present with slowly progressive weakness, and a significant proportion of individuals demonstrate cardiomyopathy, such that surveillance for arrhythmia or conduction defects may allow early treatment (eg, pacemaker, ICD); Cardiac transplantation may be necessary in individuals with severe forms of cardiomyopathy	14662268; 14660611; 15668942; 16427346; 17337483; 20627570; 20809097 
LDHA	6535	3939	Glycogen storage disease XI	AR	Pediatric		Biochemical; Dermatologic; Musculoskeletal; Renal	Biochemical; Musculoskeletal; Renal		Individuals can have exertional myoglobinuria, and renal failure has been reported, such that precautions (eg, involving exercise) may be beneficial	7449146; 3092644; 3383424; 2334430; 1959923; 1999544
LDHB	6541	3945	Lactate dehydrogenase B deficiency	AR	N/A	N/A	Biochemical	General		The clinical significance is unclear	5119336; 6383647; 2334429; 70259; 10509905; 11509017 
LDLR	6547	3949	Hypercholesterolemia, familial	AD/AR	Pediatric		Cardiovascular	Cardiovascular		Dietary and medical measures to lower cholesterol levels may be beneficial; In severe instances, therapy may include plasma apharesis, and gene therapy has been described	3020025; 3155573; 3924410; 3012527; 3549308; 3815525; 3818645; 3343347; 2837085; 3263645; 2563635; 2569482; 2544509; 2088165; 1978682; 1999337; 1863993; 1609792; 1734722; 8098448; 8054972; 9016531; 9645910; 10422803; 11246453; 10631147; 10882754; 11453971; 11600564; 11298688; 15657370; 17335829; 17215532; 18400033; 18354102; 20703241; 20686565; 21722902; 21872251; 21925044; 22244043; 22698793; 22881376; 22893714; 23054246
LDLRAP1	18640	26119	Hypercholesterolemia, familial, autosomal recessive	AR	Pediatric		Cardiovascular; Dermatologic	Cardiovascular		Interventions to maintain lipid profiles at a more desirable level can decrease morbidity/mortality, such as relates to CAD	11326085; 15599766; 21872251 
LEFTY2	3122	7044	Left-right axis malformations	AD	N/A	N/A	Cardiovascular; Pulmonary	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10053005
LEMD3	28887	23592	Buschke-Ollendorff syndrome; Osteopoikilosis 	AD	N/A	N/A	Dermatologic; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12749062; 15489854; 17223882; 17087626; 19438932; 20618940; 20732851; 21985280 
LEP	6553	3952	Leptin deficiency	AR	Pediatric		Endocrine	Endocrine	Heterozygotes may display milder forms of disease	Severely affected individuals may benefit from treatment with leptin	9202122; 9745435; 9500540; 10486419; 11281277; 11689931; 15070752; 17986612; 17206122; 19427251; 20382689; 22463805 
LEPR	6554	3953	Leptin receptor deficiency	AR	Pediatric		Allergy/Immunology/Infectious; Endocrine	Allergy/Immunology/Infectious; Endocrine	Standard treatments for obesity, such as gastric surgery, have been described as beneficial	In addition to endocrine manifestations, individuals may be susceptible to infections (eg, respiratory infections), which, coupled with other manifestations (eg, severe obesity) can have severe sequelae such that prophylaxis and rapid treatment may be beneficial	8666155; 9537324; 17229951; 21306929; 23275530; 23616257
LFNG	6560	3955	Spondylocostal dysostosis, autosomal recessive 3	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16385447; 20301771
LGI1	6572	9211	Epilepsy, familial temporal lobe, 1	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8773604; 11906506; 12205652; 11810107; 15079010; 15079011; 17562837; 19064878; 20301709; 21444903; 21504429; 22496201 
LHB	6584	3972	Hypogonadism, hypergonadotropic; Female infertility and oligo-amenorrhea	AD/AR	Pediatric		Endocrine	Endocrine		Homozygous/compound heterozygous males may not undergo spontaneous puberty, and treatment (eg, with HCG) can be beneficial; Females may be affected with infertility and oligo-amenorrhea, and medical treatmetn (eg, with HCG) may be beneficial	429481; 1727547; 7904610; 7714098; 9457942; 15602022; 19129711 
LHCGR	6585	3973	Leydig cell hypoplasia type I; Leydig cell hypoplasia type II; Luteinizing hormone resistance, female; Precocious puberty, male	AR	Pediatric		Endocrine; Genitourinary; Oncologic	Endocrine; Genitourinary; Oncologic	 Both germline and somatic mutations have been described	In mild forms of LCH, the disorder may not be clinically recognized early, and exogenous testosterone can result in normal virilization; In Precocious puberty, male, medical therapy (eg, with combined spironolactone and testolactone) has been reported as beneficial; Surveillance for related neoplasms (eg, testicular neoplasms) may allow prompt diagnosis and treatment	184390; 6792847; 3557461; 3812586; 2492636; 7692306; 7719343; 7581384; 8559204; 8923827; 9703386; 9817592; 10580072; 10714363; 10704433; 11391350; 11857565; 19129711; 21060208; 21683950; 21720050; 22369774; 22931948 
LHFPL5	21253	222662	Deafness, autosomal recessive 67	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	16752389; 16459341
LHX3	6595	8022	Pituitary hormone deficiency, combined, 3	AR	Pediatric		Audiologic/Otolaryngologic; Endocrine; Musculoskeletal; Neurologic	Audiologic/Otolaryngologic; Endocrine		Medical treatment of endocrine deficiencies, which can include congenital hypothyroidism and ACTH deficiency, can be beneficial; Awareness of hearing impairment can allow prompt interventions related to speech and language development	10835633; 16394081; 17327381; 18407919; 22238406; 22286346 
LHX4	21734	89884	Pituitary hormone deficiency, combined, 4	AD	Pediatric		Endocrine; Neurologic; Musculoskeletal; Pulmonary	Endocrine		Individuals can prevent neonatally with severe manifestations due to endocrine anomalies such as hypoglycemia; Respiratory distress has also been described at presentation; Other corrections of endocrine anomalies, such as growth hormone deficiency treatment, can be beneficial	11567216; 17527005; 18073311; 19856252; 20534763; 22232309; 23029363; 23761422
LIAS	16429	11019	Pyruvate dehydrogensae lipoic acid synthetase deficiency	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22152680
LIFR	6597	3977	Stuve-Wiedemann syndrome	AR	N/A	N/A	Musculoskeletal; Neurologic	General	Individuals can have temperature control anomalies and other manifestations of dysautonomia	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4105362; 8728692; 9382147; 9674905; 9674906; 12514358; 14740318; 18546280; 19371797; 20447141 
LIG4	6601	3981	LIG4 syndrome; Severe combined immunodeficiency with sensitivity to ionizing radiation	AR	Pediatric		Allergy/Immunology/Infectious; Craniofacial; Hematologic; Musculoskeletal; Neurologic; Oncologic	Allergy/Immunology/Infectious; Hematologic; Oncologic		Antiinfectious prophylaxis and early and aggressive treatment of infections and hematologic anomalies may be beneficial; Oncologic disorders have also been described, and surveillance may allow prompt treatment	11779494; 15333585; 16088910; 16357942 
LIM2	6610	3982	Cataract 19	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11917274
LINS	30922	55180	Mental retardation, autosomal recessive 27	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21937992; 23773660
LIPA	6617	3988	Cholesterol ester storage disease; Wolman disease	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal	Cardiovascular		Treatment with HMG-CoA reductase inhibitors may be effective for management of atherosclerotic risk in milder forms of the condition; Enzyme replacement therapy (eg, with sebelipase alfa) has been described; HSCT has been described	14008104; 5642714; 5477680; 859064; 2347551; 1528002; 8254026; 8146180; 8617513; 18174560; 18776925; 19214773; 19308038; 21291321; 21963785; 22227072; 23007684; 23035117; 23348766; 23999269; 24072694; 24122380
LIPC	6619	3990	Hepatic lipase deficiency	AR	Pediatric		Cardiovascular	Cardiovascular		Surveillance and treatment for cholesterol and cardiovascular perturbations may decrease morbidity and mortality	1883393; 1671786; 12777476; 19428034 
LIPE	6621	3991	Abdominal obesity-metabolic syndrome 4	AR	Pediatric		Cardiovascular; Endocrine	Cardiovascular	Heterozygous individuals may also demonstrate findings including dyslipidemia and insulin resistance	Among other manifestations, individuals have been described with dyslipidemia, and awareness may allow surveillanec and early management	24848981
LIPH	18483	200879	Hypotrichosis 7	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17095700; 17333281; 18445047; 19365138; 19892526; 21426374; 23590372
LIPI	18821	149998	Hypertriglyceridemia, familial	AD	Pediatric		Cardiovascular	Cardiovascular		Surveillance and treatment for cholesterol and cardiovascular perturbations may decrease morbidity and mortality	12719377
LIPN	23452	643418	Ichthyosis, congenital, autosomal recessive 8	AR	N/A	N/A	Dermatologic	General	There are suggestions that treatment may be tailored by more precise (ie, genetic) diagnosis	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12780701; 21439540
LITAF	16841	9516	Charcot-Marie-Tooth disease, type 1C	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11713717; 12525712; 19541485; 20301384; 23319192
LMAN1	6631	3998	Combined factor V and VIII deficiency	AR	Pediatric		Hematologic	Hematologic		Individuals can suffer from bleeding diatheses of varying severity, and preventive measures related to bleeding episodes can be beneficial	13575936; 14452289; 4638375; 564138; 9045860; 9546392; 16304051; 18391077; 18685427; 19787799; 23006835 
LMBR1	13243	64327	Acheiropody; Syndactyly, type IV; Laurin-Sandrow syndrome; Triphalangeal thumb, type I; Polydactyly, preaxial type II; Triphalangeal thumb-polysyndactyly syndrome; Tibial aplasia/hypoplasia; Hypoplastic or aplastic tibia with polydactyly	AD/AR	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal	General	Conditions may involve mutations in a SHH-regulatory element within an LMBR1 intron	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5808544; 1132167; 1155460; 1163539; 6660253; 10937618; 10780921; 11090342; 12837695; 16059937; 17152067; 17476456; 17300748; 18463159; 18178630; 18417549; 19291772; 20068592; 20569257; 22495965; 24456159; 24965254
LMBRD1	23038	55788	Methylmalonic aciduria and homocystinuria, cblF type	AR	Pediatric		Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Dermatologic; Hematologic; Neurologic	Biochemical		While no treatment is completely effective, specific dietary (eg, high-calorie, low protein diet and avoidance of fasting, with measures taken to avoid/treat decompensation)  and other medical measures (eg, cofactor therapy with hydroxycobalamin) may be beneficial to treat and prevent sequelae in the acute and chronic states	4001945; 3725502; 20301503; 19136951; 20127417; 21910240; 21303734; 22065268; 20446115 
LMF1	14154	64788	Combined lipase deficiency	AR	Pediatric		Cardiovascular; Endocrine; Gastrointestinal	Cardiovascular; Endocrine; Gastrointestinal		Individuals may present with severe hypertryglceridemia, with findings including gastrointestinal manifestations (abdominal pain, emesis, recurrent pancreatitis, hepatosplenomegaly), as well as  eruptive xanthomata and lipemia retinalis, and dietary measures (fat restriction) and medical treatment (eg, gemfibrozil, omega-3 fatty acid supplementation) can be beneficial; Individuals may also manifest with diabetes mellitus, which can benefit from standard treatment (and which may also help with other manifestations)	17994020; 19820022 
LMNA	6636	4000	Cardiomyopathy, dilated, 1A; Heart-hand syndrome, Slovenian type; Emery-Dreiffus muscular dystrophy, autosomal dominant; Emery-Dreiffus muscular dystrophy, autosomal recessive; Muscular dystrophy, congenital, LMNA-related; Limb-girdle muscular dystrophy type 1B; Malouf syndrome; Lipodystrophy, familial partial, 2 (Dunnigan type)	AD/AR 	Pediatric	Allelic with Hutchinson-Guilford Progeria (AD);  Restrictive dermopathy, lethal (AD); Charcot-Marie-Tooth disease, axonal, type 2B1 (AR); Mandibuloacral dysplasia with type A lipodystrophy (AR)	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Hematologic; Musculoskeletal; Neurologic	Cardiovascular	Some allelic conditions are clinically recognizable, and in these, it is not clear if early (genetic) diagnosis would be additionally beneficial	Some LMNA-associated conditions can include cardiac anomalies, including arrhythmias and cardiomyopathy that can precede other obvious clinical signs/symptoms, and medical (eg, ICD placement) management prior to severe sequelae may be beneficial	4362786; 1205025; 3519971; 2957478; 9920078; 10080180; 10580070; 10662742; 10587585; 10814726; 10843151; 10814726; 10655060; 10739751; 11231979; 11799477; 12075506; 12768443; 12629077; 12673789; 12927431; 12702809; 12714972; 12920062; 14627682; 12788894; 12628721; 15028826; 15148145; 15317753; 15286156; 15961312; 15622532; 15668447; 16407522; 16278265; 17136397; 17250669; 17848409; 17469202; 17150192; 17325275; 17377071; 18256394; 18551513; 18364375; 18348272; 18805829; 19084400; 19283854; 21483645; 20301582 ; 20301717; 20301609; 20301300; 20301462; 22199124; 22177269; 22224630; 22240398; 22274718; 22431096; 22491857; 22700598; 22806367 
LMNB1	6637	4001	Leukodystrophy, adult-onset, autosomal dominant	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16951681;  21225301; 23649844
LMX1B	6654	4010	Nail-patella syndrome	AD	Pediatric	Allelic with Focal segmental glomerulosclerosis (AD)	Dermatologic; Musculoskeletal; Ophthalmologic; Renal	Ophthalmologic; Pharmacogenomic; Renal	Onset may typically be during adulthood, though surveillance earlier may be warranted given reports of affected individuals in the 3rd decade	Individuals may have open-angle glaucoma, and surveillance and appropriate treatment may be beneficial; Agents that may contribute to glaucoma (as well as NSAIDs as relates to renal function) should be avoided; Medical treatment (eg, ACE inhibitors) may be beneficial in terms of affecting the progression of renal disease; Renal transplantation has been described	9590287; 9618165; 15928687; 17515884; 18414507; 20301311; 21850167; 23687361
LOR	6663	4014	Vohwinkel syndrome, variant form	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8673107; 9326323; 9326398; 16403113 
LOXHD1	26521	125336	Deafness, autosomal recessive 77	AR	N/A	N/A	Audiologic/Otolaryngologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19732867; 23226338 
LPA	6667	4018	Lipoprotein A deficiency, congenital	AR	N/A	N/A	General	General		The clinical relevance is unclear	7726859; 10484779; 15523644; 16840570; 16267501; 20032323
LPAR6	15520	10161	Hypotrichosis 8	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18461368; 18297070; 18297072; 21070332; 21426374
LPIN1	13345	23175	Myoglobinuria, acute, recurrent, autosomal recessive	AR	Pediatric		Musculoskeletal; Renal	Musculoskeletal; Pharmacogenomic; Renal		Attacks are typically trigerred by illnesses rather than exercise, and avoidance of fasting and prompt treatment of febrile illness may prevent severe sequelae such as renal failure; Anesthesia precautions can be beneficial in order to decrease the risk of malignant hyperthermia	6851679; 1544519; 18817903
LPIN2	14450	9663	Majeed syndrome	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Hematologic	Allergy/Immunology/Infectious; Hematologic		Individuals may manifest with Chronic recurrent multifocal osteomyelitis (CRMO), for which treatment with NSAIDs/corticosteroids may be beneficial; Individuals may require surveillance and blood transfusion treatment for anemia	11381255; 17011878; 17330256; 18055821; 20301735; 22559933; 22570351
LPL	6677	4023	Lipoprotein lipase deficiency; Combined hyperlipidemia, familial; Hyperlipoproteinemia, type I	AD/AR	Pediatric		Cardiovascular; Gastrointestinal; Hematologic	Cardiovascular; Gastrointestinal; Pharmacogenomic	Heterozygous variants can contribute to Familial combined hyperlipidemia (LPL deficiency is an autosomal recessive disorder)	In LPL deficiency, treatment centers on medical nutrition therapy (eg, reducing fat intake, alcohol abstinence, as well as antioxidant therapy related to risks of sequelae) aimed to maintain plasma triglyceride concentration less than 1000 mg/dL; In LPL deficiency, gene therapy (Alipogene tiparvovec) is clinically available; Treatment of acute pancreatitis involves fasting with low-calorie infusion; Medical treatment (eg, with fibrates) may be beneficial in adults with LPL deficiency; Certain medications that can affect triglyceride levels should be avoided, and sequelae such as pancreatitis may be precipitated by OCPs;	13483896; 13712364; 3630977; 4719678; 6638056; 6645961; 2648155; 2536938; 2110364; 2294743; 1969408; 2121025; 1975597; 2394828; 2010533; 1702428; 1907278; 1752947; 1674945; 2038366; 1530621; 1562620; 1400331; 1598907; 1511985; 1639392; 1512512; 1731801; 1737848; 8096693; 8486765; 8325986; 7906986; 8541837; 7753827; 8755931; 8778602; 9401010; 9738727; 10517255; 10199753; 11134145; 11334614; 15928243; 16174715; 15840743; 16552344; 17032721; 19295657; 20301485; 21159338; 22129523; 22239554; 22438229; 22717743; 23527320; 24142281
LRAT	6685	9227	Leber congenital amaurosis 14; Retinitis pigmentosa, juvenile; Retinal-dystrophy, early-onset severe; Retinitis punctata albescens	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11381255; 17011878; 18055821; 22559933; 22570351 
LRBA	1742	987	Common variable immunodeficiency 8, with autoimmunity	AR	Pediatric		Allergy/Immunology/Infectious; Cardiovascular; Hematologic	Allergy/Immunology/Infectious; Hematologic	The condition may include infectious and autoimmune manifestations	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; The condition may include autoimmune phenomena including hematologic manifestations (eg, thrombocytopenia, anemia), and surveillance and early diagnosis and treatment may be beneficial	22608502
LRIG2	20889	9860	Urofacial syndrome 2	AR	Pediatric		Craniofacial; Neurologic; Renal	Renal	Wilms tumor has been reported in one individual	Individuals have been described with manifestations including  low-capacity, overactive bladder, vesicoureteral reflux, hydronephrosis, urosepsis, and  renal impairment, though treatment attempts (eg, with intermittent catheterization, antimuscarinic agents, and surgical bladder augmentation) were not reported as  slowing slow renal failure, and dialysis was required in at least one individual; Early recognition may allow management aimed at preserving renal function	23313374
LRIT3	24783	345193	Night blindness, congenital stationary (complete), 1F, autosomal recessive	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23246293
LRP1	6692	4035	Schizophrenia	AD	N/A	N/A	Neurologic	General		Evidence or clinical applicability is unclear	21743468
LRP2	6694	4036	Donnai-Barrow syndrome; Faciooculoacousticorenal syndrome	AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic; Renal	Audiologic/Otolaryngologic; General	The condition can involve multiple congenital anomalies	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	8266995; 9475100; 12923867; 17632512; 18553518; 20301732 
LRP4	6696	4038	Cenani-Lenz syndactyly syndrome; Sclerosteosis 2	AD/AR	N/A	N/A	Craniofacial; Musculoskeletal; Renal	General	Cenani-Lenz syndactyly syndrome can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7891385; 9182770; 10756427; 11260233; 11385236; 14577675; 12868467; 18978656; 20381006; 21471202
LRP5	6697	4041	van Buchem disease, type 2; Osteopetrosis, autosomal dominant 1; Osteosclerosis; Hyperostosis, endosteal; Exudative vitreoretinopathy 4; Osteoporosis-pseudoglioma syndrome	AD/AR/Digenic	N/A	N/A	Musculoskeletal; Ophthalmologic	General	Digenic inheritance (with FZD4) has been reported in Exudative vitreoretinopathy	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8832721; 9056564; 9831343; 10434540; 11719191; 12015390; 11741193; 12054167; 12579474; 15346351; 15024691; 15981244; 20301326; 21407258; 21600326; 22456437; 22487062; 23077402 
LRP6	6698	4040	Coronary artery disease, autosomal dominant 2	AD	Pediatric		Cardiovascular	Cardiovascular	While severe manifestations may occur later in life, surveillance and preventive measures may be beneficial prior to adulthood	Preventive measures related to control of contributing factors associated with coronary artery disease may be beneficial to reduce morbidity and mortality	17332414; 23703864
LRPAP1	6701	4043	Myopia 23, autosomal recessive	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23830514
LRPPRC	15714	10128	Leigh syndrome, French-Canadian type	AR	N/A	N/A	Biochemical; Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8392290; 8392291; 12529507; 21266382
LRRC6	16725	23639	Ciliary dyskinesia, primary 19	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	23122589
LRRC8A	19027	56262	Agammaglobulinemia 5	AD	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious	Only one individual (with a translocation affecting LRRC8A) has been described; This individual also demonstrated dysmorphic facies in addition to agammaglobulinemia	Congenital agammaglobulinemia has been described, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	14660746
LRRK2	18618	120892	Parkinson disease 8; Dementia, Lewy body	AD	N/A	N/A	Neurologic	General	Response to levodopa has been documented	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15541309; 16437584; 16437559; 19458969
LRSAM1	25135	90678	Charcot-Marie-Tooth disease, axonal, type 2P	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20865121; 22012984; 22781092
LRTOMT	25033	220074	Deafness, autosomal recessive 63	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	17166180; 17066295; 18953341; 18794526
LTBP2	6715	4053	Glaucoma 3, primary congenital, D; Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma; Weill-Marchesani syndrome 3	AR	Pediatric		Cardiovascular; Craniofacial; Musculoskeletal; Ophthalmologic	Cardiovascular; Ophthalmologic; Pharmacogenomic		Surveillance, early diagnosis, and treatment of manifestations such as ectopicia lentis and glaucoma with surgical interventions (with the use of pre and postoperative agents to control intraocular pressure), or, if surgery is not effective, drainage implants or cyclodestruction, may be effective to decrease morbidity and mortality related to vision loss;  Individuals with cardiovascular manifestations including pulmonary and aortic stenosis have been described, and awareness may allow early diagnosis and treatment; Agents that may contribute to glaucoma, as well as alpha-2-agonists, should be avoided	18776954; 19361779; 19656777; 20179738; 20301293; 20301314; 20617341; 21081970; 22025892; 22539340; 23401661
LTBP3	6716	4054	Tooth agenesis, selective, 6	AR	N/A	N/A	Dental; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19344874
LTBP4	6717	8425	Cutis laxa with severe pulmonary, gastrointestinal, and urinary abnormalities	AR	N/A	N/A	Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Pulmonary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19836010
LTC4S	6719	4056	Asthma, aspirin-induced, susceptibility to	AR	Pediatric	 	General	Pharmacogenomic		The relative risk/odds ratios of identified variants are overall relatively low, but variants may have pharmacogenomic importance	10970818; 19862937; 22884858; 23101307
LYRM4	21365	57128	Combined oxidative phosphorylation deficiency 19	AR	N/A	N/A	Biochemical; Neurologic	General	Severe neonatal lactic acidosis has been described, but it is unclear if specific causative knowledge would be helpful in management (in one individual, supportive treatment in infancy has been described as beneficial)	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23814038
LYRM7	28072	90624	Mitochondrial complex III deficiency, nuclear type 8	AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24014394
LYST	1968	1130	Chediak-Higashi syndrome	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Hematologic; Neurologic; Oncologic	Allergy/Immunology/Infectious; Hematologic; Oncologic		Individuals can have infection susceptibility, and prophylaxis and early and aggressive treatment of infections can be beneficial; Surveillance for hematologic complications and malignancy is warranted; For the accelerated phase, chemoimmunotherapy then  transition to continuation therapy can be beneficial; For bleeding, platelet transfusions and DDAVP may be beneficial to prevent and/or treat  episodes; BMT/HSCT has been described	13584476; 5908967; 5156632; 5064229; 711501; 2697195; 2070553; 2058369; 8030398; 8701696; 9215680; 10422800; 10527680; 11857544; 15790783; 20503323; 20301751; 21488161; 23521865
LYZ	6740	4069	Amyloidosis, systemic nonneuropathic	AD	N/A	N/A	Dermatologic; Gastrointestinal; Renal	General	The treatment of amyloidosis differs depending on the genetic cause (and genetic diagnosis may additionally help avoid relatively high-risk treatment regimens), and in lysozyme amyloidosis, liver and renal transplantation may be beneficial, but it is not clear that early (genetic) diagnosis would be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8464497; 15745733; 21988333 
LZTFL1	6741	54585	Bardet-Biedl syndrome 17	AR	N/A	N/A	Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition may involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17163542; 22510444; 23692385
LZTR1	6742	8216	Schwannomatosis 2	AD	Adult		Oncologic	Oncologic		Individuals are susceptible to schwannomas, and knowledge may allow early management	24362817
MAB21L2	6758	10586	Microphthalmia, syndromic 14	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24906020
MAF	6776	4094	Cataract 21, multiple types	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11772997; 16470690
MAFB	6408	9935	Multicentric carpotarsal osteolysis	AD	N/A	N/A	Craniofacial; Musculoskeletal; Renal	General	Individuals frequently have progressive renal disease	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22387013
MAGT1	28880	84061	Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia	XL	Pediatric	Allelic with Mental retardation, X-linked 95 (XL)	Allergy/Immunology/Infectious; Neurologic	Allergy/Immunology/Infectious	For Mental retardation, X-linked 95, the evidence of mutations as being related to disease causation has been questioned due to subsequent population-based studies	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	18455129; 21796205; 23871722
MAK	6816	4117	Retinitis pigmentosa 62	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21835304
MALT1	6819	10892	Immunodeficiency 12	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals have been described as suffering from primary immunodeficiency including infantile-onset recurrent bacterial and candidal infections, and awareness may allow prophylaxis and early and aggressive treatment of infections	23727036; 24332264
MAMLD1	2568	10046	Hypospadias 2, X-linked	XL	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17086185
MAN1B1	6823	11253	Mental retardation, autosomal recessive 15	AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20345473; 21763484; 21063731
MAN2B1	6826	4125	Mannosidosis, alpha B, lysosomal	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic		Though the disorder may be clinically recognizable, manifestations can include immunodeficiency, and prophylactic vaccines and early and aggressive treatment of infections can be beneficial; Some individuals may manifest with early-onest hearing impairment, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	4358183; 995502; 724292; 6860058; 4082921; 1472354; 8357013; 7702090; 9158146;  9758606; 11014473; 15534274; 18651971; 20301570; 22161967
MANBA	6831	4126	Mannosidosis, beta A, lysosomal	AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3762648; 2945113; 2079835; 1623631; 1499588; 8285582; 59034; 9384606; 12468273; 16401745; 17420068; 18565776; 19728872; 22369051 
MAOA	6833	4128	Brunner syndrome	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8211186; 8503438; 20485326; 22365943; 24169519
MAP2K1	6840	5604	Cardiofaciocutaneous syndrome	AD	Pediatric		Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Neurologic; Oncologic	Cardiovascular; Oncologic		Surveillance and treatment related to  manifestations such as cardiac anomalies can be beneficial; Individuals may be at increased malignancy risk (eg, an individual with hepatoplastoma has been described), and awareness may allow prompt recognition and treatment of oncologic sequelae	16439621; 17551924; 17567882; 18456719; 18042262; 20301303; 20301365; 21495173
MAP2K2	6842	5605	Cardiofaciocutaneous syndrome	AD	Pediatric		Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Oncologic	Cardiovascular; Oncologic		Surveillance and treatment related to  manifestations such as cardiac anomalies can be beneficial; Individuals with malignancies have been reported (eg, hematologic malignancies), and awareness of increased risk may be beneficial in order to allow prompt detection and management	16439621; 8456719; 18042262; 20301365; 20358587; 21178588; 21495173 
MAP3K1	6848	4214	46,XY Sex Reversal 6	AD	Pediatric		Endocrine; Genitourinary; Oncologic	Genitourinary; Oncologic		Surveillance and surgical treatment of gonadal tumors can reduce morbidity	12476449; 21129722
MAPK10	6872	5602	Epileptic encephalopathy, Lennox-Gastaut type	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16249883; 23329067
MAPK8IP1	6882	9479	Diabetes mellitus	AD	N/A	N/A	Endocrine	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10700186
MAPT	6893	4137	Supranuclear palsy, progressive; Frontotemporal dementia; Parkinson-dementia sydnrome; Pick disease	AD/AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1416801; 7936288; 7936241; 7977375; 9029080; 9781517; 9789048; 10202939; 9443491; 9641683; 9708963; 9932968; 10072441; 10412802; 10534245; 10388790; 11134398; 11117542; 11445645; 11710889; 11601501; 11220749; 12177383; 12056930; 14595660; 12913211; 14991829; 15792962; 16195395; 10388790; 16278856; 17923640; 17310038; 18703462; 19884571; 19884572; 19786698; 21295377; 21555888; 21558644; 21943955; 22109955; 22482453; 22699846 
MARS	6898	4141	Infantile liver failure syndrome 2	AR	Pediatric		Biochemical; Endocrine; Gastrointestinal; Hematologic; Neurologic; Pulmonary	Hematologic	Only one individual has been described	While the condition may involve multiple issues related to medical care, the described individual had transfusion-dependent anemia, and awareness may allow prompt recognition and treatment	24103465
MARVELD2	26401	153562	Deafness, autosomal recessive 49	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	15538632; 17186462; 18084694
MASP1	6901	5648	3MC syndrome 1	AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic 	Audiologic/Otolaryngologic	The condition can include multiple congenital anomalies	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	690758; 17937425; 18266249; 21035106; 21258343
MASP2	6902	10747	MASP2 deficiency	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Surveillance and early treatments for autoimmune phenomena may be beneficial; Infectious sequelae have been reported, but the relation to immunosuppresion regimens is unclear	12904520; 19767106; 20338057
MASTL	19042	84930	Thrombocytopenia 2	AD	Pediatric		Hematologic	Hematologic		Individuals may have bleeding tendency, and precautions (eg, in surgical situations) may be beneficial	10891439; 12890928; 22102272 
MAT1A	6903	4143	Methionine adenosyltransferase deficiency	AD/AR	Pediatric		Biochemical; Neurologic	Biochemical		While the disorder frequently does not have severe sequelae, and therapy may not be required for many individuals, in some, dietary measures (eg, methionine restriction) may be beneficial; AdoMet therapy has also been described as beneficial	1191305; 7229751; 7271238; 3812486; 3339126; 1683972; 1527987; 7573050; 7560086; 8770875; 9042912; 9482646; 12705496
MATN3	6909	4148	Spondyloepimetaphyseal dysplasia, matrilin-3 related; Epiphyseal dysplasia, multiple, 5	AD/AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13849708; 11479597; 11528506; 12884427; 15121775; 14729835; 15948199; 18205203; 20301302; 21922596; 21965141 
MATR3	6912	9782	Amyotrophic lateral sclerosis 21	AD	N/A	N/A	Audiologic/Otolaryngologic; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9837826; 19344878
MAX	6913	4149	Pheochromocytoma	AD	Pediatric		Oncologic	Oncologic		Surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of neoplasms, which may may reduce morbidity and mortality	21685915
MBD5	20444	55777	Mental retardation, autosomal dominant 1	AD	N/A	N/A	Craniofacial; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17847001; 21981781
MBL2	6922	4153	Mannose-binding protein deficiency	AD	Pediatric	 	Biochemical	Pharmacogenomic		Low MBL levels are associated with increased risk of infection in young children, cancer patients undergoing chemotherapy, and organ-transplant patients treated with immunosuppressive regimens, especially liver transplant recipients	21871896
MBTPS2	15455	51360	Keratosis follicularis spinulosa decalvans, X-linked; IFAP syndrome with or without BRESHECK syndrome; Palmoplantar keratoderma, mutilating, with periorificial keratotic plaques, X-linked	XL	N/A	N/A	Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	IFAP syndrome with or without BRESHECK syndrome can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1552542; 10398262; 10694306; 8745901; 18984066; 19361614; 20672378; 22105905; 24313295
MC1R	6929	4157	Increased analgesia from kappa-opioid receptor agonist, female specific	AD	Pediatric	Allelic with Skin/hair/eye pigmentation, variation in, 2 (AD)	General	Pharmacogenomic	Skin/hair/eye pigmentation, variation in may not have actionable relevance, though there may be increased risk of skin cancer	Variants may have pharmacogenomic relevance, as results suggest that women with 2 variant MC1R alleles demonstrate  greater analgesia from  kappa-opioid pentazocine	7581459; 8894704; 11030758; 10631149; 11487574; 11500805; 11500806; 12876664; 12839583; 12663858; 16809487; 17952075; 19578364; 21693730; 21128237; 22095472; 22561518 
MC2R	6930	4158	Glucocorticoid deficiency 1	AR	Pediatric		Endocrine	Endocrine		Early recognition and preventive measures and treatment related to hypoglycemia (as well as to potential infectious episodes) can be effective	13616862; 4302512; 4312011; 4342294; 4349230; 238474; 2539720; 8094489; 8227361; 7627261; 12851305; 21823545; 22337906; 22814974 
MC4R	6932	4160	Obesity, autosomal dominant	AD	N/A	N/A	Endocrine	General	Biallelic mutations have been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9771698; 9771699; 10199800; 10577903; 11487744; 12646665; 12499395; 12646666; 14764818; 16507637; 16492696; 20957447; 20966905; 21047921; 21921657; 22463805 
MCCC1	6936	56922	3-Methylcrotonyl-CoA carboxylase 2 deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		Therapy may not be necessary/effective in some individuals, but medical (eg, carnitine, glycine) and dietary (eg, low protein, leucine restricted) therapy may be beneficial in some individuals; Precautions in the setting of stressors such as viral illnesses may be beneficial	4194964; 5035417; 1000869; 6441868; 2515383; 1779635; 1517917; 8598648; 9187484; 10485305; 11181649; 11170888; 11893004; 16835865; 17968484; 21734494; 22264772; 22642865 
MCCC2	6937	64087	3-Methylcrotonyl-CoA carboxylase 2 deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		Therapy may not be necessary/effective in some individuals, but medical (eg, carnitine, glycine) and dietary (eg, low protein, leucine restricted) therapy may be beneficial in some individuals; Precautions in the setting of stressors such as viral illnesses may be beneficial	7128647; 1293382; 8598650; 8831079; 9544913; 11181649; 11170888; 15877210; 16835865; 17968484; 22030835; 22264772; 22642865 
MCEE	16732	84693	Methylmalonyl-CoA epimerase deficiency	AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	Biochemical	No response to vitamin B12 administration was documented in the affected individual	Long-term dietary (high-calorie diet low in propiogenic amino acid precursors with carnitine supplementation) and medical management (eg, IM hydroxocobalamin, antibiotics to decrease propionate production) is indicated; Fasting and high-protein consumption should be avoided; In the emergent setting, prompt recognition and appropriate metabolic care may be beneficial to decrease morbidity and mortality; Antioxidants for optic nerve atrophy may be beneficial; Liver/kidney transplant has been described in methylmalonic acidemia	16752391; 17823972; 20301409
MCFD2	18451	90411	Factor V & Factor VIII, combined deficiency of	AR	Pediatric		Hematologic	Hematologic		Preventive measures and prompt treatment of bleeding diathese may reduce morbidity; Medical treatment to replace absent factors can be effective (eg, with FFP for FV, Desmopression or FVIII concentrates/recombinant products/plasma-derived factor for FVIII)	12717434; 15333032; 16304051; 19141160; 18391077; 21492322; 22535353 
MCM6	6949	4175	Lactose intolerance, adult type; Lactase persistence	AD	N/A	N/A	Biochemical; Gastrointestinal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7543318; 9481112; 11788828; 12915462; 15114531; 16041375; 15928901; 16019716; 17120047; 17159977; 18179885
MCOLN1	13356	57192	Mucolipidosis IV	AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4365943; 166049; 7114093; 3918453; 2438637; 1789285; 9323557; 9600972; 9710036; 10973263; 11030752; 15523648; 17239335; 19006653; 20159435 
MCPH1	6954	79648	Microcephaly, primary autosomal recessive, 1	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7693575; 12046007; 11857108; 15199523; 16311745; 20978018; 20101680; 21668957 
MECP2	6990	4204	Rett syndrome; Encephalopathy, neonatal severe, due to MECP2 mutations; Autism, X-linked 3; Mental retardation, X-lnked syndromic 13; Angelman-like syndrome; Mental retardation, X-linked 79	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5300597; 8651288; 9377804; 9326329; 9637791; 10508514; 10232754; 10398236; 10577905; 10986043; 11106359; 12615169; 11071498; 11022934; 11768391; 11309367; 11402105; 11746022; 11913564; 11930274; 11807877; 11885030; 12325019; 12615169; 12770674; 14598336; 12615169; 12615169; 15034579; 16077729; 15689435; 16080119; 17172942; 16965328; 17088400; 16690727; 16832102; 17712354; 17351020; 18477000; 18989701; 19194883; 18985075; 20035514; 19365833; 20425814; 21154482; 21104896; 22415763; 22578097; 22581587
MED12	11957	9968	Lujan-Fryns syndrome; Opitz-Kaveggia syndrome; Mental retardation, X-linked, with Marfanoid habitus; FG syndrome; Ohdo syndrome	XL	N/A	N/A	Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic	General	Aortic root dilatation and ventricular septal defect were reported in one individual and his maternal uncle	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4365204; 6711603; 3322000; 10405444; 10508979; 17036352; 17334363; 17369503; 18973276; 19938245; 20301719; 20507344; 20981778; 23395478
MED13L	22962	23389	Transposition of the great arteries, dextro-looped 1; Congenital heart defects and intellectual disability; Intellectual disability, autosomal recessive	AD/AR	N/A	N/A	Cardiovascular; Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14638541; 21937992; 23403903 
MED17	2375	9440	Microcephaly, postnatal progressive, with seizures and brain atrophy	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20950787
MED23	2372	9439	Mental retardation, autosomal recessive 18	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21868677
MED25	28845	81857	Charcot-Marie-Tooth disease, axonal, tybe 2B2	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19290556
MEF2C	6996	4208	Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations	AD	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19876902; 19592390; 20412115; 20513142;  23001426
MEFV	6998	4210	Familial Mediterranean fever	AD/AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Musculoskeletal; Renal	Allergy/Immunology/Infectious	It has been described that heterozygous mutations, while potentially contributing to/causing certain autoinflammatory disorders, do not cause classic (Mendelian) Familial Mediterranean fever, but may act as risk alleles (susceptibility factors) for clinically similar forms of disease	Individuals may present with periodic fever, pain (including abdominal pain, arthritis, pleurisy), and rash,and medical treatment aimed at reducing inflammation (eg, with colchicine, TNF-alpha antibodies, IL-1 decoy receptor agents) can be effective (and additional considerations related to medical treatment prior to and during pregnancy may be beneficial); BMT has been reported	14162896; 4437392; 4636899; 4783424; 921085; 6822630; 3966749; 3306755; 3515182; 3694919; 8434621; 8831074; 9288094; 9288758; 9415347; 9266193; 9450890; 10528243; 10787449; 12130485; 12529300; 14679589; 15024744; 16632148; 20301405; 23075349; 23070486; 23463692; 23508419; 23505238; 23521609; 23710607; 23716950; 23742958;  23800337; 23844200
MEGF10	29634	84466	Myopathy, early-onset, areflexia, respiratory distress, and dysphagia	AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17236770; 22101682; 22371254; 23453856 
MEGF8	3233	1954	Carpenter syndrome 2	AR	N/A	N/A	Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal 	General	The condition can include multiple malformations, including cardiac and genitourinary malformations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23063620
MEN1	7010	4221	Multiple endocrine neoplasia type I; Hyperparathyroidism, familial primary	AD	Adult		Endocrine; Oncologic	Endocrine; Oncologic		Surveillance and early detection of and treatment for neoplasms, as well as related sequelae may allow treatment (eg, with PPIs/somatostatin analogs, as well as appropriate and tailored surgical interventions and follow-up), and may decrease morbidity and mortality	6108714; 2857681; 9215689; 9103196; 9236523; 9215690; 9463336; 9683585; 9554741; 9832038; 9506756; 9709923; 9792884; 10439966; 10193936; 11344233; 11739416; 11295574; 12417605; 12050235; 11836268; 12112656; 12791038; 15531478; 14871962; 15240620; 15292304; 14985373; 17879353; 20301710; 22522645; 22549346; 22581216; 22584706; 23052745; 23376981; 23443490; 23645327; 23652667; 23809488; 23919339; 23956349; 23961499; 24014011; 24037737; 24058102
MEOX1	7013	4222	Klippel-Feil syndrome 2	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23290072; 24073994
MERTK	7027	10461	Retinitis pigmentosa 38	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11062461; 11727200; 17301963; 22180149 
MESP2	29659	145873	Spondylocostal dysostosis 2, autosomal recessive	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15214000; 15122512; 18485326; 20301771
MET	7029	4233	Renal cell carcinoma, papillary	AD	Adult		Oncologic	Oncologic		Surveillance and/or awareness of cancer risk may yield early detection of neoplasms may allow early treatment, which may reduce morbidity and mortality	9140397; 9563489; 9731534; 19402075; 22717761
METTL23	26988	124512	Mental retardation, autosomal recessive 44	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24501276; 24626631
MFN2	16877	9927	Charcot-Marie-Tooth disease, type 2A2; Hereditary motor and sensory neuropathy VI	AD/AR	N/A	N/A	Neurologic; Ophthalmologic	General		Charcot-Marie-Tooth disease, type 2A2 typically (though not always) results from heterozygous mutations; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9409358; 11148244; 12601114; 15136675; 15064763; 16043786; 16087932; 16835246; 16437557; 17309650; 18946002; 20008656; 19889647; 21715711; 22206013; 22526351; 22546700; 22653593; 22762946; 22957060 
MFRP	18121	83552	Microphthalmia, isolated 5; Nanophthalmos 2; Retinitis pigmentosa, autosomal recessive	AR	N/A	N/A	Ophthalmologic	General	Individuals are at risk for ophthalmologic features such as retinal detachment	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1258954; 15976030; 17167404; 18554571; 19526372; 20361016; 21810984; 22565643; 22605927; 23112574 
MFSD8	28486	256471	Ceroid lipofuscinosis, neuronal, 7	AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15074367; 15965709; 17564970; 19277732,; 19201763; 18850119; 22612257 
MGAT2	7045	4247	Congenital disorder of glycosylation, type IIa	AR	Pediatric		Audiologic/Otolaryngologic; Biochemical; Craniofacial; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	7944531; 8808595; 11228641; 19419693; 20684000; 22105986; 23023920
MGME1	16205	92667	Mitochondrial DNA depletion syndrome 11	AR	Pediatric		Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic	Cardiovascular		In addition to other manifestations, the condition has been described as including cardiovascular sequelae (eg, dilated cardiomyopathy, arrhythymias), and awareness may allow appropriate surveillance and prompt management	23313956
MGP	7060	4256	Keutel syndrome	AR	N/A	N/A	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6468443; 3717211; 2515061; 9674914; 9916809; 15810001
MIB1	21086	57534	Left ventricular noncompaction 7	AD	Pediatric		Cardiovascular	Cardiovascular		Left ventricular noncompaction may manifest as depressed systolic function, with potential complications including arrhythmias, systemic embolism, heart failure and sudden death, and surveillance (eg, with echocardiogram and electrocardiogram) may allow early diagnosis and treatment	23314057
MICU1	1530	10367	Myopathy with extrapyramidal signs	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24336167
MID1	7095	4281	Opitz GBBB syndrome	XL	N/A	N/A	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9354791; 11030761; 12833403; 15121778; 15558842; 16619207; 20301502; 20671548; 22407675 
MID2	7096	11043	Mental retardation, X-linked 101	XL	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24115387
MIP	7103	4284	Cataract 15, multiple types	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10802646
MIR17HG	23564	407975	Feingold syndrome 2	AD	N/A	N/A	Musculoskeletal; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21892160
MIR184	31555	406960	Keratoconus with cataract	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14638698; 16735990; 21996275; 22131394
MIR96	31648	407053	Deafness, autosomal dominant 50	AD	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic	Hearing loss was progressive, and was described in the earliest reported affected at 12 years in one family, while it occurred as early as 2-3 years of age in another family	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	14757864; 19363479
MITF	7105	4286	Waardenburg syndrome, type 2A; Tietz albinism-deafness syndrome; Melanoma, cutaneous malignant, susceptibility to, 8; Renal cell carcinoma with or without malignant melanoma	AD	Pediatric (Waardenburg syndrome, type 2A; Tietz albinism-deafness syndrome); Adult (Melanoma, cutaneous malignant, susceptibility to, 8; Renal cell carcinoma with or without malignant melanoma)	Variants may be associated with Melanoma, cutaneous malignant, susceptibility to, 8 (AD); Renal cell carcinoma with or without malignant melanoma (AD) (The OR of melanoma and/or RCC has been reported as >14 in one study) (AD)	Audiologic/Otolaryngologic; Dermatologic; Ophthalmologic; Oncologic	Audiologic/Otolaryngologic; Oncologic	Waardenburg syndrome be clinically recognizable in some individuals; Digenic inheritance (with TYR) has been reported	For Waardenburg syndrome, type 2A and Tietz albinism-deafness syndrome, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; For Melanoma, cutaneous malignant, susceptibility to and Renal cell carcinoma with or without malignant melanoma, awareness may allow preventive measures, surveillance, and early diagnosis and treatment of disease	13985019; 5006208; 331943; 666627; 7951321; 7874167; 7702105; 7573125; 8589691; 9158138; 10851256; 18510545; 20024939; 22012259; 22080950; 23167872; 23414473; 23774529; 23802662; 24638154; 24767713
MKKS	7108	8195	McKusick-Kaufman syndrome; Bardet-Biedl syndrome 6	AR 	N/A	N/A	Cardiovascular; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The conditions frequently involve multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Variants may modify severity of BBS and related disorders due to mutations in other BBS-associated genes	14172277; 5694533; 5545396; 7262101; 7246610; 2681663; 2564737; 8209897; 10465109; 10973251; 11102925; 10802661; 11567139; 12837689; 15637713; 16104012; 20301537; 20301675;
MKRN3	7114	7681	Central precocious puberty	AD	N/A	N/A	Endocrine	General	In Precocious puberty, treatment with gonadotropin-releasing hormone receptor analogs/LHRH agonists can be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Variants may modify severity of BBS and related disorders due to mutations in other BBS-associated genes	23738509
MKS1	7121	54903	Meckel syndrome, type 1; Bardet-Biedl syndrome 13	AR 	N/A	N/A	Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Neurologic; Musculoskeletal; Ophthalmologic; Renal	General	The conditions frequently involve multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Variants may modify severity of BBS and related disorders due to mutations in other BBS-associated genes	6486167; 16415886; 17377820; 17935508; 18327255; 19515853; 20301537
MLC1	17082	23209	Megalencephalic leukoencephalopathy with subcortical cysts	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11254442; 12939431; 18757878; 20301707; 20560255; 21145992; 21160490; 21487377; 22416245; 22552818; 24824219
MLH1	7127	4292	Colorectal cancer, hereditary nonpolyposis, type 2; Mismatch repair cancer syndrome; Endometrial cancer; Muir-Torre syndrome	AD/AR	Adult (Colorectal cancer, hereditary nonpolyposis, type 2; Endometrial cancer; Muir-Torre syndrome)/Pediatric (Mismatch repair cancer syndrome)		Dermatologic; Oncologic	Oncologic	Individuals may be at risk for a number of types of cancer; Variants may also contribute to cancer susceptibility in the general population	In HNPCC, or surveillance, colonoscopy with polyp removal is indicated starting at (whichever is earlier) age 20-25 years or 10 years prior to the earliest familial diagnosis; Prophylactic Hysterectomy with bilateral oophorectomy may be considered after childbearing is completed; For individuals with colon cancer, surgical treatment with full colectomy (and ileorectal anastomosis) is recommended; Cigarette smoking should be avoided; For other tumor types (indiviudals may be at risk for a number of cancer types), awareness of cancer risk may allow early diagnosis and treatment, which may reduce morbidity and mortality; Individuals with Mismatch repair cancer syndrome are at risk of multiple types of malignancy, and awareness may allow early detection and management	6020987; 5684233; 4063166; 7815421; 8128251; 8145827; 7661930; 8751876; 9634524; 9927033; 10072435; 10577927; 15264268; 15077197; 16042583; 15520370; 15662714; 15235030; 17440981; 18457354; 19156169; 20301390; 24434690
MLH3	7128	27030	Colorectal cancer, hereditary nonpolyposis type 7; Endometrial carcinoma	AD	Adult		Oncologic	Oncologic	The clinical significance of mutations in this gene is unclear	Surveillance to allow early detection and treatment of tumors (associated with colorectal cancer) may be beneficial to reduce morbidity and mortality	12702580; 16885347
MLPH	29643	79083	Griscelli syndrome, type 3	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12148598; 12897212
MLYCD	7150	23417	Malonyl-CoA decarboxylase deficiency	AR	Pediatric		Biochemical; Cardiovascular; Neurologic	Biochemical; Cardiovascular		Dietary measures (low-fat, high-carbohydrate diet, with one report describing benefit from long-chain triglyceride restriction and medium-chain triglyceride supplementation) can normalize urinary organic acid excretion and prevent hypoglycemic episodes; During infectious/febrile illnesses, inpatient care to reduce morbidity and mortalitiy may be beneficial; Surveillance for cardiac manifestations may allow early management, which may be beneficial	6145813; 3709568; 8259873; 10417274; 9869665; 10455107; 12955715; 16275149; 20549361; 22104738; 22778304 
MMAA	18871	166785	Methylmalonic acidemia, cblA type	AR	Pediatric		Biochemical; Hematologic; Neurologic; Ophthalmologic	Biochemical		Long-term dietary (high-calorie diet low in propiogenic amino acid precursors with carnitine supplementation) and medical management (eg, IM hydroxocobalamin, antibiotics to decrease propionate production) is indicated; Fasting and high-protein consumption should be avoided; In the emergent setting, prompt recognition and appropriate metabolic care may be beneficial to decrease morbidity and mortality; Antioxidants for optic nerve atrophy may be beneficial; Liver/kidney transplant has been described in methylmalonic acidemia	6132336; 12438653; 20301409; 21545677; 23026888
MMAB	19331	326625	Methylmalonic acidemia, cblB type	AR	Pediatric		Biochemical; Hematologic; Neurologic; Ophthalmologic	Biochemical		Long-term dietary (high-calorie diet low in propiogenic amino acid precursors with carnitine supplementation) and medical management (eg, IM hydroxocobalamin, antibiotics to decrease propionate production) is indicated; Fasting and high-protein consumption should be avoided; In the emergent setting, prompt recognition and appropriate metabolic care may be beneficial to decrease morbidity and mortality; Antioxidants for optic nerve atrophy may be beneficial; Liver/kidney transplant has been described in methylmalonic acidemia	7213387; 12471062; 16410054; 20301409; 20301503; 20556797; 21416195
MMACHC	24525	25974	Methylmalonic aciduria and homocystinuria, cblC type	AR	Pediatric		Biochemical; Cardiovascular; Dermatologic; Hematologic; Neurologic; Ophthalmologic; Renal	Biochemical		While no treatment is completely effective, specific dietary (eg, high-calorie, low protein diet and avoidance of fasting, with measures taken to avoid/treat decompensation)  and other medical measures (eg, cofactor therapy) may be beneficial to treat and prevent sequelae in the acute and chronic states	5779140; 6749192; 3257264; 2368803; 9266389; 11258350; 10399092; 11320193; 12210350; 16311595; 16714133; 17431913; 17853453; 20301503; 19370762; 20631720; 21748409; 21835369; 23837176
MMADHC	25221	27249	Methylmalonic aciduria and homocystinuria, cblD type	AR	Pediatric		Biochemical; Hematologic; Neurologic; Ophthalmologic	Biochemical		While no treatment is completely effective, specific dietary (eg, high-calorie, low protein diet and avoidance of fasting, with measures taken to avoid/treat decompensation)  and other medical measures (eg, cofactor therapy) may be beneficial to treat and prevent sequelae in the acute and chronic states	5524089; 2339678; 15292234; 18385497; 20301409; 20301503; 22156578
MMP13	7159	4322	Spondyloepimetaphyseal dysplasia, Missouri type; Metaphyseal anadysplasia 1 	AD/AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16167086; 19615667; 24781753
MMP2	7166	4313	Torg-Winchester syndrome; Nodulosis-arthropathy-osteolysis	AR	N/A	N/A	Dermatologic; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5795345; 2625626; 9843039; 10861676; 10861675; 11431697; 15691365; 16542393; 17059372; 20720557; 20865259; 22876575 
MMP20	7167	9313	Amelogenesis imperfecta, hypomaturation type, IIA2	AR	N/A	N/A	Dental	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3150442; 15744043; 21597265; 23355523  
MMP9	7176	4318	Metaphyseal anadysplasia 2	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4252978; 1867263; 19615667
MN1	7180	4330	Meningioma, familial	AD	Pediatric		Oncologic	Oncologic	A balanced genomic disruption (translocation) has been reported as causative	Surveillance/early treatment may improve outcomes	2014801; 7731706
MNX1	4979	3110	Currarino syndrome	AD	Pediatric		Gastrointestinal; Genitourinary; Musculoskeletal; Oncologic; Renal	Oncologic	The condition can involve multiple congenital anomalies	While congenital malformations often allow clinical recognition, individuals can have presacral teratomas, which can undergo malignant transformation, and awareness may allow prompt detection and management	6789651; 2059799; 9843207; 10749657; 11528505; 15216552; 16906559; 17612791
MOCS1	7190	4337	Molybdenum cofactor deficiency, type A	AR	Pediatric		Biochemical; Neurologic; Ophthalmologic	Biochemical		The disorder can have severe neurologic sequelae, and the use of substitution therapy (with IV-administered purified cyclic pyranopterin monophosphate) has been reported as showing benefit in biochemical parameters as well as clinical/neurologic manifestations	9731530; 10053004; 10327149; 16021469; 20385644; 21031595 
MOCS2	7193	4338	Molybdenum cofactor deficiency, type B	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11746050; 16021469; 16429380; 19544009; 21031595 
MOG	7197	4340	Narcolepsy 7	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21907016
MOGS	24862	7841	Congenital disorder of glycosylation, type IIb	AR	Pediatric		Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Hematologic; Musculoskeletal; Neurologic	Hematologic	Hepatic-metabolized agents should be avoided	At least theoretically, awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	10788335; 20301507; 24716661
MPC1	21606	51660	Mitochondrial pyruvate carrier deficiency	AR	N/A	N/A	Biochemical; Craniofacial;  Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12649063; 22628558
MPDU1	7207	9526	Congenital disorder of glycosylation, type If	AR	Pediatric		Biochemical; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	Hematologic	Hepatic-metabolized agents should be avoided	At least theoretically, awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	11733556; 11733564;  20301507
MPDZ	7208	8777	Hydrocephalus, nonsyndromic, autosomal recessive 2	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23240096
MPI	7216	4351	Congenital disorder of glycosylation, type Ib 	AR	Pediatric		Biochemical; Gastrointestinal; Hematologic	Biochemical; Hematologic	Hepatic-metabolized agents should be avoided	Treatment with oral mannose can result in clinical improvement;  Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	9585601; 9525984; 10484808; 10980531; 11134235; 12414827; 18285818; 19065443; 19101627; 20301507; 20679665 
MPL	7217	4352	Thrombocythemia 2; Amegakaryocytic thrombocytopenia	AD/AR	Pediatric		Hematologic; Oncologic	Hematologic; Oncologic		For Thrombocythemia 2, manifestations may include thrombotic/hemorrhagic episodes, as well as leukemic transformation, and surveillance and prompt treatment may be beneficial; For Amegakaryocytic thrombocytopenia, individuals may have findings such as severe bleeding complications, and platelet transfusion can be beneficial; Effective SCT has been described	9029014; 10077649; 11133753; 14764528; 15269348; 16351641; 17054430
MPLKIP	16002	136647	Trichothiodystrophy, nonphotosensitive 1	AR	N/A	N/A	Allergy/Immunology/Infectious; Dental; Dermatologic; Genitourinary; Neurologic; Ophthalmologic	Allergy/Immunology/Infectious 		A number of individuals have been reported with frequent infections, and awareness and prompt and aggressive treatment of infections may be beneficial	4847854; 984047; 2333887; 15645389; 1634754; 16977596; 18603627; 21959366
MPO	7218	4353	Myeloperoxidase deficiency	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Many individuals (including with complete myeloperoxidase deficiency) do not show obvious clinical sequelae, but increased candiasis and incidence of severe infections has been reported in some individuals, and awareness may allow prompt recognition and treatment, which may reduce morbidity and mortality	5796360; 4983030; 4109818; 6260268; 6267975; 6280744; 6321554; 2462938; 7904599; 15507752; 15108282; 17017121; 18453132; 17614858; 17650507; 23228855
MPV17	7224	4358	Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)	AR	Pediatric		Biochemical; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic	Biochemical; Gastrointestinal; Oncologic		Glycemic control (eg, with cornstarch) has been shown to slow the progression of hepatic disease; Liver transplanation has been described, though the efficacy is unclear; Awareness of the possible risk of hepatocellular carcinoma may be beneficial	16909392; 16582910; 18695062; 19520594; 19012992; 20074988; 22593919; 21511859 
MPZ	7225	4359	Charcot-Marie-Tooth disease, dominant intermediate 3; Charcot-Marie-Tooth disease, axonal, type 2J; Charcot-Marie-Tooth disease, axonal, type 2I; Neuropathy, congenital hypomyelinating; Roussy-Levy syndrome; Dejerine-Sottas disease; Charcot-Marie-Tooth disease, type 1B 	AD	N/A	N/A	Neurologic	General	Individuals with biallelic mutations have also been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7693129; 8310815; 8664899; 8816708; 9595994; 9537424; 10329755; 10071056; 10406984; 10214757; 10553995; 10965800; 11080237; 10764043; 11835375; 14638973; 15159512; 15326256; 15642860; 16488608; 16775239; 17663472; 21326314,; 21280073; 22222859; 22622165; 22633464; 22691094; 22734905 
MR1	4975	3140	Paroxysmal nonkinesigenic dyskinesia	AD	N/A	N/A	Neurologic	General	Medical treatment (eg, with benzodiazepines) have been described as beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8659518; 9490305; 15496428; 15262732; 15824259; 16216955; 17515540; 19124534; 22967746 
MRAP	1304	56246	Glucocorticoid deficiency 2	AR	Pediatric		Endocrine	Endocrine		Cortisol treatment can be effective to pevent manifestations such as hypoglycemia or severe sequelae of infectious episodes in infancy/childhood	15654338; 16868047; 20427498; 21951701 
MRE11A	7230	4361	Breast cancer, susceptibility to	AD	Adult	Allelic with Ataxia-telangiectasia-like disorder 1 (AR)	Dermatologic; Neurologic; Oncologic; Ophthalmologic	Oncologic	Individuals with Ataxia-telangiectasia-like disorder 1 may be at increased risk for malignancy, though the data are unclear	Awareness of the risk of malignancy may allow early surveillance, preventive measures, and early diagnosis and treatment of disease	8445618; 8684395; 10612394; 11196167; 11371508; 15269180; 15574463; 17932350; 19383352; 19584272; 19732584; 20087742; 21227757; 21799032; 22006311; 22863007; 24549055; 24894818
MRPL3	10379	11222	Combined oxidative phosphorylation deficiency 9	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21786366
MRPL44	16650	65080	Mitochondrial cardiomyopathy, autosomal recessive	AR	Pediatric		Cardiovascular; Gastrointestinal; Musculoskeletal	Cardiovascular		Individuals have been reported as teenagers with hypertrophic cardiomyopathy (as well as with infantile-onset hyptertrophic cardiomyopathy), and surveillance for cardiomyopathy (eg, with echocardiography/electrocardiography) may allow early detection and  medical treatment of disease manifestations	23315540
MRPS16	14048	51021	Combined oxidative phosphorylation deficiency 2	AR	N/A	N/A	Biochemical; Gastrointestinal; Neurologic	General	The described dysmorphic features may have been coincident (the patient was born to consanguineous parents) as relates to the mitochondrial disorder	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15505824
MRPS22	14508	56945	Combined oxidative phosphorylation deficiency 5	AR	N/A	N/A	Biochemical; Cardiovascular; Renal; Musculoskeletal; Neurologic	General	Described dysmorphic features in one patient may have been coincident (the patient was born to consanguineous parents) as relates to the mitochondrial disorder	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17873122; 21189481
MS4A1	7315	931	Immunodeficiency, common variable, 5	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may be susceptible to recurrent infections (eg, respiratory infections have been reported), and antiinfectious prophylaxis (including with IVIG therapy) and early and aggressive treatment of infections may be beneficial	20038800
MSH2	7325	4436	Colorectal cancer, hereditary nonpolyposis, type 1; Endometrial cancer; Mismatch repair cancer syndrome; Muir-Torre syndrome	AD/AR	Adult (Colorectal cancer, hereditary nonpolyposis, type 1; Endometrial cancer; Muir-Torre syndrome)/Pediatric (Mismatch repair cancer syndrome)		Dermatologic; Oncologic	Oncologic	Homozygous/compound heterozygous mutations have been described in individuals with severe disease; Variants in PMS1 thought to be associated with hereditary colon cancer were found to co-segregate in individuals with MSH2 mutations; Variants may also contribute to cancer susceptibility, and individuals may be at risk for a number of cancer types	In HNPCC, For surveillance, colonoscopy with polyp removal is indicated starting at (whichever is earlier) age 20-25 years or 10 years prior to the earliest familial diagnosis; Prophylactic Hysterectomy with bilateral oophorectomy may be considered after childbearing is completed; For individuals with colon cancer, surgical treatment with full colectomy (and ileorectal anastomosis) is recommended; Cigarette smoking should be avoided; For other tumor types (individuals may be at risk for a number of cancer types), awareness of cancer risk may allow early diagnosis and treatment, which may reduce morbidity and mortality; Individuals with Mismatch repair cancer syndrome are at risk of multiple types of malignancy, and awareness may allow early detection and management	6020987; 5684233; 4016686; 2029018; 8484121; 8252616; 8261515; 8484120; 8072530; 8931714; 9218993; 9593786; 9634524; 9843200; 10534628; 10190329; 10196371; 11600610; 11112663; 11809679; 12549480; 12650804; 14574010; 14994245; 15520370; 14871915; 15235030; 15872208; 15662714; 15937084; 16807412; 16372347; 16511680; 17539897; 17327285; 19419416; 20093870; 20301390; 20591884; 23612316; 23729658; 23891921; 23990280; 24434690
MSH3	7326	4437	Endometrial carcinoma	AD	Adult		Oncologic	Oncologic	Individuals may be at risk for a number of types of cancer	In HNPCC, for surveillance, colonoscopy with polyp removal is indicated starting at (whichever is earlier) age 20-25 years or 10 years prior to the earliest familial diagnosis; Prophylactic Hysterectomy with bilateral oophorectomy may be considered after childbearing is completed; For individuals with colon cancer, surgical treatment with full colectomy (and ileorectal anastomosis) is recommended; Cigarette smoking should be avoided; For other tumor types (individuals may be at risk for a number of cancer types), awareness of cancer risk may allow early diagnosis and treatment, which may reduce morbidity and mortality; Individuals with Mismatch repair cancer syndrome are at risk of multiple types of malignancy, and awareness may allow early detection and management	9354786; 12732731; 15098177; 15340263; 16000562; 16283678; 17557300; 24434690
MSH6	7329	2956	Colorectal cancer, hereditary nonpolyposis type 5; Mismatch repair cancer syndrome; Endometrial cancer	AD/AR	Adult (Colorectal cancer, hereditary nonpolyposis type 5; Endometrial cancer)/Pediatric (Mismatch repair cancer syndrome)		Oncologic	Oncologic		In HNPCC, for surveillance, colonoscopy with polyp removal is indicated starting at (whichever is earlier) age 20-25 years or 10 years prior to the earliest familial diagnosis; Prophylactic Hysterectomy with bilateral oophorectomy may be considered after childbearing is completed; For individuals with colon cancer, surgical treatment with full colectomy (and ileorectal anastomosis) is recommended; Cigarette smoking should be avoided; For other tumor types, awareness of cancer risk may allow early diagnosis and treatment, which may reduce morbidity and mortality; Individuals with Mismatch repair cancer syndrome are at risk of multiple types of malignancy, and awareness may allow early detection and management	9354786; 12732731; 15098177; 15340263; 16000562; 16283678; 17557300
MSR1	7376	4481	Barrett esophagus/esophageal adenocarcinoma; Prostate cancer	AD	Adult		Gastrointestinal; Oncologic	Gastrointestinal; Oncologic	While some (eg, common) variants may increase the risk of prostate cancer slightly, others appear to confer much higher risk	Awareness of disease risk may allow surveillance, preventive measures (eg, related to Barrett esophagus) and early treatment of malignancy, which may reduce morbidity and mortality	11443539; 12244320; 12839931; 12958598; 15536476; 16287155; 17768178; 17903305; 18398045; 20086112; 21791690
MSRB3	27375	253827	Deafness, autosomal recessive 74	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	19650862; 21185009
MSTN	4223	2660	Muscle hypertrophy	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15215484
MSX1	7391	4487	Orofacial cleft 5; Tooth agenesis, selective, 1, with/without orofacial cleft; Witkop syndrome	AD	N/A	N/A	Craniofacial; Dental; Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8696335; 10742093; 11369996; 12097313; 12807959; 15264286; 15354328; 16327884; 16498076; 16868654; 16932841; 18374898; 19346736; 21297014; 21626677; 22297032 
MSX2	7392	4488	Craniosynostosis, type 2; Parietal foramina with cleidocranial dysplasia; Parietal foramina	AD	N/A	N/A	Craniofacial; Musculoskeletal	General	Upstream microduplications have been described as causing Cleidocranial dysplasia	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8106171; 8357019; 10742103; 14571277; 16222674; 16319823; 16642368; 17955513; 18000908; 19533795; 21082653 
MT-ATP6	7414	4508	Neuropathy, ataxia, and retinitis pigmentosa; Leber hereditary optic neuropathy; Ataxia and polyneuropathy, adult-onset; Cardiomyopathy, infantile hypertrophic; Leigh syndrome; Striatonigral degeneration, infantile, mitochondrial	Maternal	N/A	N/A	Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	General	Mitochondrial mutations may involve a variety of sequelae, including cardiovascular manifestations such as cardiomyopathy	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2137962; 1436530; 1550128; 8095070; 8250532; 8042671; 8554662; 7726182; 7668837; 8739943; 9199572; 9329425;  9501263; 9631394; 9556461; 10417290; 10590437; 10604142; 10676807; 11245730; 11730668; 11843698; 17452590; 19124644; 19188198; 22231385; 22577227; 22773856
MT-ATP8	7415	4509	Brain pseudoatrophy, reversible, valproate-induced, susceptibility to	Maternal	Pediatric	Allelic with Cardiomyopathy, apical hypertrophic,  and neuropathy (Maternal); Cardiomyopathy, infantile hypertrophic	Biochemical; Cardiovascular; Neurologic	Pharmacogenomic	Variants can also be associated with a range of typical mitochondrial-related phenotypes, including cardiac manifestations such as cardiomyopathy	Medication selection would be impacted in mutation-positive individuals	17101920; 17954552; 19188198
MT-CO1	7419	4512	Deafness, mitochondrial	Maternal	Pediatric	Allelic with Myoglobinuria, recurrent (maternal); Leber hereditary optic neuropathy (maternal); Sideroblastic anemia (maternal); Cytochrome C oxidase deficiency (maternal)	Audiologic/Otolaryngologic; Biochemical; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Audiologic/Otolaryngologic; Pharmacogenomic	In some individuals, aminoglycoside administration can result in deafness; Cosegregation with other variants may result in disease	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment, with highly variable age of onset, and for individuals with early-onset hearing impairment, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Aminoglycosides should be avoided	1634041; 10577941; 10980727; 12140182
MT-CO2	7421	4513	Cytochrome c oxidase deficiency	Maternal	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10205264
MT-CO3	7422	4514	Myoglobinuria, recurrent	Maternal	N/A	Allelic with Cytochrome c oxidase deficiency (Maternal); Leber hereditary optic neuropathy (Maternal)	Biochemical; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8240356; 8630495; 10788526; 11063732
MT-ND1	7455	4535	Deafness, mitochondrial	Maternal	Pediatric	 Allelic with  Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (Maternal); Leber hereditary optic neuropathy (Maternal); Leber optic atrophy and dystonia (Maternal)	Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	Audiologic/Otolaryngologic	As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment, with highly variable age of onset, and for individuals with early-onset hearing impairment, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	1928099; 2018041; 1674640; 1732158; 10519336; 15466014; 15505787; 17562939; 18216301; 21625124; 21723259; 21968326; 22079202; 22241583; 22577081
MT-ND2	7456	4536	Leber hereditary optic neuropathy; Mitochondrial complex I deficiency	Maternal	N/A	N/A	Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	General	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1732158; 20454697; 21145289 
MT-ND3	7458	4537	Leber optic atrophy and dystonia; Mitochondrial complex I deficiency	Maternal	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19458970
MT-ND4	7459	4538	Leber hereditary optic neuropathy; Leber optic atrophy and dystonia; Mitochondrial complex I deficiency	Maternal	N/A	N/A	Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	General	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	201231; 2566116; 1763894; 2039048; 8644732; 18216301 
MT-ND4L	7460	4539	Leber hereditary optic neuropathy	Maternal	N/A	N/A	Biochemical; Ophthalmologic	General	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11935318
MT-ND5	7461	4540	Myoclonic epilepsy with ragged red fibers; Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes; Leber hereditary optic neuropathy; Mitochondrial complex I deficiency	Maternal	N/A	N/A	Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	General	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment; As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1900003; 1732158; 8213825; 8016139; 18524835
MT-ND6	7462	4541	Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes; Oncocytoma; Leber hereditary optic neuropathy; Leber optic atrophy and dystonia; Mitochondrial complex I deficiency	Maternal	N/A	N/A	Biochemical; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3736869; 1417830; 8016139; 8644732; 11781695; 14735585; 16380132; 18524835; 21555623
MT-RNR1	7470	4549	Deafness, mitochondrial	Maternal	Pediatric		Audiologic/Otolaryngologic; Biochemical; Cardiovascular	Audiologic/Otolaryngologic; Pharmacogenomic	In some individuals, aminoglycoside administration can result in deafness; Individuals have also been reported with cardiomyopathy	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment, with highly variable age of onset, and for individuals with early-onset hearing impairment, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Aminoglycosides should be avoided	7689389; 9039999; 9887373; 9490575; 10326749; 10577941; 9915970; 10521300; 10788333; 11079536; 11313749; 12372057; 12920080; 12624722; 15286157; 14755216; 14681830; 15555598; 15637703; 15708009; 16380089; 16458854; 16631122; 16375862; 16782057; 17341440; 18261986; 18983818
MT-RNR2	7471	4550	Chloramphenicol toxicity/resistance	Maternal	Pediatric	 	General	Pharmacogenomic		Medication selection would be impacted in mutation-positive individuals; Sensitivity to streptomycin has been suggested as well	14233236; 5785754; 6273808; 7219548
MT-TC	7477	4511	Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes	Maternal	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	General	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8829635; 9185178; 17241783; 17724295; 18386806; 18800376 
MT-TE	7479	4556	Diabetes-deafness syndrome; Mitochondrial myopathy, infantile, transient; Mitochondrial myopathy with diabetes	Maternal	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Craniofacial; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic	General	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4114165; 7726154; 9353617; 15048886; 19720722; 21194154; 21931168
MT-TF	7481	4558	Myoclonic epilepsy with ragged red fibers; Nephropathy, tubulointerstitial; Encephalopathy, mitochondrial; Epilepsy, mitochondrial; Myopathy, mitochondrial; Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes	Maternal	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Renal	General	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment; As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15184630
MT-TL1	7490	4567	Brain pseudoatrophy, reversible, valproate-induced, susceptibility to	Maternal	Pediatric	Allelic with Cytochrome c oxidase deficiency (Maternal); Myoclonic epilepsy with ragged red fibers (Maternal); Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (Maternal); Diabetes-deafness syndrome (Maternal); Cyclic vomiting syndrome (Maternal); SIDS, susceptibility to (Maternal)	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General; Pharmacogenomic	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment; As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection	In Brain pseudoatrophy, reversible, valproate-induced, susceptibility to, variants may have pharmacogenomic importance, as medication selection would be impacted in mutation-positive individuals; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1514779; 1360090; 8254046; 9243242; 9506761; 10482110; 10519336; 10699170; 11708999; 12905015; 15466014; 16326995; 16476929; 17101920
MT-TS1	7497	4574	Deafness	Maternal	Pediatric	Allelic with Myoclonic epilepsy with ragged red fibers (maternal); Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (maternal)	Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	Audiologic/Otolaryngologic; Pharmacogenomic	In some individuals, aminoglycoside administration can result in deafness	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment, with highly variable age of onset, and for individuals with early-onset hearing impairment, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Aminoglycosides should be avoided	8019558; 10340654; 10371545; 11175301
MTAP	7413	4507	Diaphyseal medullary stenosis with malignant fibrous histiocytoma	AD	Pediatric		Musculoskeletal; Oncologic	Oncologic		Individuals are at high risk for aggressive bone sarcoma, and surveillance and early treatment may be beneficial to reduce morbidity and mortality	4713573; 3745248; 8680521; 8781110; 16244874; 22464254
MTFMT	29666	123263	Combined oxidative phosphorylation deficiency 15	AR	Pediatric		Cardiovascular; Neurologic; Ophthalmologic	Cardiovascular		Among other multi-systemic manifestations, the condition may include cardiac manifestations such as Wolff-Parkinson-White syndrome, and surveillance may allow early diagnosis and management	21907147; 23499752; 24461907
MTHFD1	7432	4522	Severe combined immunodeficiency	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Hematologic; Neurologic; Renal	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical		Individuals have been described as presenting with severe and recurrent infections, as well as other sequelae, such as renal disease, and medical management (with folate and hydroxycobalamin) has been described as beneficial;  In addition to folate and hydroxycobalamin treatment, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Related to hearing deificits, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	23296427
MTHFR	7436	4524	Homocystinuria due to MTHFR deficiency	AR	Pediatric		Biochemical; Cardiovascular; Hematologic; Neurologic	Biochemical; Cardiovascular; Hematologic	 Variants in MTHFR may interact with variants in other genes, such as F5 to result in susceptibility to hematologic manifestations	Medical therapy (eg, with folate, betaine, riboflavin, hydroxycobalamin) can be effective; In individuals with heterozygous mutations, there may be an increased risk of thrombophilia, and considerations may be warranted in certain situations 	3889647; 1998339; 1866027; 1627352; 8456826; 7920641; 7647779; 7726158; 7564788; 8691945; 8826441;  8892013; 8940272; 8994411; 9133512; 9341863; 9244205; 9372726; 9068801; 9878639; 10323741; 10384377; 10536004;  10679944; 10862840; 10923034; 10961793; 11508552; 11170082; 11274424; 11938441; 12142069; 12673793; 15896655; 15979034; 16145688; 16216822; 17409006; 18658082; 18708589;  19697151; 20236116; 20356773; 20850942; 22578003; 22646290; 22665071; 22721898; 22773907; 22807619; 22856671; 22947400; 23124942
MTM1	7448	4534	Myopathy, centronuclear, X-linked	XL	Pediatric		Gastrointestinal; Hematologic; Musculoskeletal; Renal	Hematologic	Increased risk of findings including subdural hemorrhage, subdural hygromas, and cephalohematomas has been reported	Among other findings affecting multiple organ systems, individuals may demonstrate a vitamin-K respondent bleeding diathesis, and surveillance and treatment may be beneficial	5816884; 8640223; 9285787; 9169146; 9305655; 10726846; 9450905; 9931531; 10502779; 10323249; 10714588; 10790201; 11552027; 12707446; 15883335; 15690409; 19197364; 20434914; 20500434; 21881007; 22101172; 22153990; 22258523;  22264517; 22520358 
MTMR2	7450	8898	Charcot-Marie-Tooth disease, type 4B1	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10802647
MTO1	19261	25821	Combined oxidative phosphorylation deficiency 10	AR	Pediatric		Biochemical; Cardiovascular; Neurologic	Biochemical		The condition can include findings such as hypertrophic cardiomyopathy, hypoglycemia, and  and lactic acidosis; Treatment with biotin, coenzyme Q10, thiamine, and dichloroacetate has been reported as beneficial in multiple individuals	22608499
MTPAP	25532	55149	Ataxia, spastic, 4, autosomal recessive	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20970105
MTR	7468	4548	Methylmalonic acidemia, cblG type	AR	Pediatric		Biochemical; Cardiovascular; Hematologic; Neurologic; Renal	Biochemical		Medical treatment may be beneficial (while hydroxycobalamin may not be as effective as in other MMA types, other treatments, such as betaine, methylfolate, and even methionine supplements may be attempted)	2897628; 2203337; 8968736; 8968737; 12068375; 20301503; 22108709 
MTRR	7473	4552	Homocystinuria-megaloblastic anemia, cobalamin E type	AR	Pediatric		Biochemical; Hematologic; Neurologic; Renal	Biochemical		Treatment (eg, with hydroxycobalamin, folate, methylcobalamin) has been reported as effective	6700644; 2860337; 3812589; 9427140; 10444342; 15060097; 15979034; 15714522 
MTTP	7467	4547	Abetalipoproteinemia	AR	Pediatric		Gastrointestinal; Hematologic; Neurologic; Ophthalmologic	Gastrointestinal		Dietary measures (eg, with a low fat diet and supplementation of essential fatty acids and fat-soluble vitamins) can be beneficial, and early initiation can prevent/decrease severe sequelae	15411425; 14925152; 13745738; 14237436; 4135110; 848999; 716878; 7425890; 6959555; 2339706; 1439810; 8361539; 9686820; 17275380; 18239027; 18611256; 20402070; 21333248; 21394827; 21502686; 23090820; 23556456; 24288038
MUSK	7525	4593	Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency	AR	Pediatric		Musculoskeletal; Neurologic	Musculoskeletal; Neurologic; Pharmacogenomic		Most individuals with CMS benefit from AChE inhibitors and/or  potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; Some individuals with SCCMS are treated with quinidine, which has some major side effects and may be detrimental in individuals with AChR deficiency	1783919; 8041349; 9120223; 8819551; 9546329; 12771277; 15496425; 15951177; 20301347 
MUT	7526	4594	Methylmalonic acidemia due to methylmalonyl-CoA mutase deficiency	AR	Pediatric		Biochemical; Hematologic; Cardiovascular; Neurologic; Ophthalmologic	Biochemical		Long-term dietary (high-calorie diet low in propiogenic amino acid precursors with carnitine supplementation) and medical management (eg, IM hydroxocobalamin, antibiotics to decrease propionate production) is indicated; Fasting and high-protein consumption should be avoided; In the emergent setting, prompt recognition and appropriate metabolic care may be beneficial to decrease morbidity and mortality; Antioxidants for optic nerve atrophy may be beneficial; Liver/kidney transplant has been described in methylmalonic acidemia	6132336; 1977311; 1970180; 1968706; 1346616; 1351030; 7681251; 15643616; 12948746; 16451139; 18563634; 20301409; 22614770; 22695176
MUTYH	7527	4595	Familial adenomatous polyposis, 2; Colorectal adenomatous polyposis, autosomal recessive, with pilomatricomas 	AR	Adult		Dermatologic; Oncologic	Oncologic	Mutations may also be inolved in susceptibility to other types of malignancies	Individuals may present with colonic neoplasia, and regular surveillance for neoplasms may allow early treatment of tumors, which may improve outcomes; In some individuals, additional surgical measures such as total colectomy with ileorectal anastomosis, may be indicated in addition to surveillance for neoplasms; In addition to colorectal neoplasms, individuals are at high risk for a number of other cancer types (including breast cancer), and awareness may allow early diagnosis and treatment	11818965; 12393807; 12853198; 12606733; 15690400; 21061173; 21063410; 21171015; 21696383; 22371070; 22658618; 22744763; 22851115; 22865608 
MVK	7530	4598	Mevalonic aciduria; Hyper-IgD syndrome	AR	Pediatric	Allelic with Porokeratosis 3, disseminated superficial actinic (AD)	Allergy/Immunology/Infectious; Dermatologic; Biochemical; Gastrointestinal	Allergy/Immunology/Infectious		In Mevalonic aciduria, diagnosis can be challenging, and effective treatment is available with specific agents (eg, steroids, leukotriene receptor antagonists); In Hyper-IgD syndrome, accurate diagnosis may be beneficial in order to avoid unnecessary surgery for suspected appendicitis/acute abdomen; Medical treatment (eg, corticosteroids, leukotriene receptor inhibitors) during the acute phase can be effective, as well as medical treatment in the non-acute phase	6144826; 3012338; 8386351; 8190036; 8973873; 10369262; 10369261; 11313769; 11742050; 15149516; 15457465; 15536479; 16835861; 18409191; 20194276; 21399979; 21548022; 22159817; 22246419; 22271696; 22983302
MYBPC1	7549	4604	Arthrogryposis, distal, type 1B; Lethal congenital contractural syndrome 4	AD/AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20045868; 22610851
MYBPC3	7551	4607	Cardiomyopathy, familial hypertrophic, 4; Cardiomyopathy, dilated; Left ventricular noncompaction 10	AD/AR	Pediatric		Cardiovascular	Cardiovascular		Surveillance in order to allow early diagnosis and treatment of cardiomyopathy can be beneficial; Cardiac transplantation has been described	7493026; 7493025; 9241277; 9562578; 10424815; 12788380; 15519027; 16199542; 16679492; 17655857; 17937428; 18337725; 19858127; 21839045; 22021246; 22314326; 22455086
MYCN	7559	4613	Feingold syndrome	AD	N/A	N/A	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Renal	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9096752; 14518066; 15821734; 16906565; 18671284; 18470948; 19852433; 20301770; 21224895; 22842076
MYD88	7562	4615	MYD88 deficiency	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals have been reported as being susceptible to severe and recurrent pyogenic bacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	18669862; 21057262; 21734245 
MYF6	7566	4618	Myopathy, centronuclear, 3	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11053684
MYH11	7569	4629	Aortic aneurysm, familial thoracic 4	AD	Pediatric		Cardiovascular	Cardiovascular		Surveillance for aortic aneurysms and related anomalies  (as well as PDA) can allow early detection and treatment, potentially decreasing morbidity and mortality	11249915; 14722581; 16444274; 17666408; 22415348; 22968129 
MYH14	23212	79784	Deafness, autosomal dominant 4; Deafness, autosomal dominant 4B; Peripheral neuropathy, myopathy, hoarseness, and hearing loss	AD	N/A	N/A	Audiologic/Otolaryngologic; Musculoskeletal; Neurologic	General	The onset of deafness has been described as postlingual	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7655461; 11938438; 15015131; 16222661; 21480433; 21368133
MYH2	7572	4620	Inclusion body myopathy 3	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11114175
MYH3	7573	4621	Arthrogryposis, distal, type 2A; Arthyrgryposis, distal, type 2B	AD	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21032118; 4975238; 5467037; 4220006; 7039311; 2803721; 9138511; 4220006; 16510655; 16642020; 18695058; 19309503; 19571066; 19684571; 20924721; 21531865 
MYH6	7576	4624	Cardiomyopathy, dilated, 1EE; Cardiomyopathy, familial hypertrophic 14	AD	Pediatric	Allelic with Atrial septal defect 3 (AD)	Cardiovascular	Cardiovascular		Permanent cardiac pacing is the only effective treatment for symptomatic/irreversible sinus node dysfunction; Sick sinus syndrome is the most common indication for permanent pacemaker implantation	11815426; 15998695; 15735645; 21378987; 22194935 
MYH7	7577	4625	Cardiomyopathy, dilated, 1S; Cardiomyopathy, familial hypertrophic; Myopathy, distal 	AD	Pediatric	Allelic with Myopathy, myosin storage (AD);  Myopathy, scapuloperoneal (AD); Laing distal myopathy (AD)	Cardiovascular; Musculoskeletal	Cardiovascular	Compound heterozygosity and digenic inheritance (with MYLK2) has been described as an explanation for severe manifestations in some individuals	Individuals can have cardiovascular anomalies, including dilated cardiomyopathy and arrhythmias, and surveillance and early treatment may be beneficial	13732753; 4104682; 1975517; 1361491; 1552912; 8254035; 8483915; 8343162; 8282798; 7909436; 8655135; 9544842; 10521296; 10424815; 11106718; 11102913; 11424919; 11733062; 11166161; 12379228; 14663035; 12975303; 12749056; 14520662; 15136674; 15322983; 16267253; 15483641; 15699387; 16684601; 16650083; 17548557; 17476457; 17336526; 18175163; 18506004; 19026577; 19138847; 19336582;  20503496; 20733148; 21395566; 21896538; 23117287; 23478172; 23956225
MYH8	7578	4626	Carney complex variant; Arthrogryposis, distal, type 7; Trismus-pseudocamptodactyly syndrome 	AD	N/A	N/A	Craniofacial; Musculoskeletal	General	In one family, cardiac and dermatologic findings appeared to co-segregate with the disease	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4443857; 4837286; 12800911; 15590965; 15282353; 17041932; 18049072; 20949528 
MYH9	7579	4627	Sebastian syndrome; May-Hegglin anomaly; Fechtner syndrome; Epstein syndrome	AD	Pediatric	Allelic with Deafness, autosomal dominant 17 (AD)	Audiologic/Otolaryngologic; Hematologic; Ophthalmologic; Renal	Hematologic		In active hemorrhage, DDAVP may decrease bleeding time; otherwise, platelet transfusion is necessary; Precautions related to bleeding risk may be beneficial	13940543; 1449176; 5011389; 2981587; 3232700; 2851314; 2176899; 1396928; 1319112; 8280620; 9390828; 9915977;10973260; 10973259; 11590545; 12533692; 12621333; 12792306; 15613099; 15667538; 16969870; 17241369; 18059020; 18284620; 19208103; 19285578; 19450438; 19860543; 20002731; 20174760; 20221761; 20301740; 20601875; 22541678; 23123319 
MYL2	7583	4633	Cardiomyopathy, familial hypertrophic, 10	AD	Pediatric	Allelic with Infantile type I muscle fibre disease and cardiomyopathy (AR)	Cardiovascular; Musculoskeletal	Cardiovascular		Medical/surgical (ICD) management may ameliorate/prevent severe sequelae	8673105; 9535554; 12404107; 21896538; 23365102 
MYL3	7584	4634	Cardiomyopathy, familial hypertrophic, 8	AD/AR	Pediatric		Cardiovascular	Cardiovascular		Early recognition may allow preventive measures and early medical management, which may ameliorate severe sequelae	6211078; 8673105; 12021217; 16267253; 21239446; 21896538 
MYLK	7590	4638	Aortic aneurysm, familial thoracic 7	AD	Pediatric		Cardiovascular	Cardiovascular		Preventive measures and medical management may be helpful to help decrease morbidity	21055718; 20301299
MYLK2	16243	85366	Cardiomyopathy, hypertrophic	AD/Digenic	Pediatric		Cardiovascular	Cardiovascular	Digenic inheritance (with MYH7) has been described	Surveillance for cardiomyopathy (eg, with echocardiography/electrocardiography) and early medical treatment may reduce morbidity	11733062
MYO15A	7594	51168	Deafness, autosomal recessive 3	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	17851452; 23226338 
MYO1A	7595	4640	Deafness, autosomal dominant 48	AD	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic	The condition has variable age of onset and severity	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	12596055; 12736868 
MYO1E	7599	4643	Focal segmental glomerulosclerosis 6	AR	N/A	N/A	Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21756023
MYO3A	7601	53904	Deafness, autosomal recessive 30	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	12032315
MYO5A	7602	4644	Griscelli syndrome, type 1	AR	N/A	N/A	Dermatologic; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9207796; 10704277; 12452176
MYO5B	7603	4645	Diarrhea 2, with microvillus atrophy	AR	Pediatric		Gastrointestinal; Renal 	Gastrointestinal; Renal 		Individuals may require nutritional support with parenteral nutrition; Renal fanconi syndrome has been described, and appropriate care of related sequelae may be beneficial	16800870; 19006234; 18724368; 21199752; 20186687; 22030065; 21206382; 22441677 
MYO6	7605	4646	Deafness, autosomal recessive 37	AR	Pediatric	Allelic with Deafness, autosomal dominant, 22 (AD), which has later onset	Audiologic/Otolaryngologic	Audiologic/Otolaryngologic	One kindred has been described also segregating hypertrophic cardiomyopathy with the MYO6 variant (H236R), but the overall evidence appears mixed as relates to cardiac findings	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	11468689; 12687499; 15060111; 18212818; 18348273; 19893302 
MYO7A	7606	4647	Deafness, autosomal recessive 2; Usher syndrome, type 1B	AR	Pediatric	Allellic with Deafness, autosomal dominant 11 (AD)	Audiologic/Otolaryngologic; Ophthalmologic	Audiologic/Otolaryngologic	The timing of onset has been reported as highly variable, though heterozygous mutations appear to result in postlingual onset	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	7951250; 87766029171832; 7870171; 9171833; 11391666;  11889386; 15221449; 18181211; 20132242; 21436283; 21150918; 23226338 
MYOC	7610	4653	Glaucoma, primary open angle, juvenile-onset	AD/AR/Digenic	Pediatric		Ophthalmologic	Ophthalmologic; Pharmacogenomic	Digenic inheritance (with CYP1B1) has been reported	Early diagnosis and treatment may be effective to decrease morbidity and mortality related to vision loss; Agents that may contribute to glaucoma should be avoided	8513321; 9005853; 9535666; 10330365; 11535458; 11709019; 11774072; 15025728; 15108121; 15733270; 17562996; 17197538; 17499207
MYOT	12399	9499	Myopathy, myofibrillar, 3	AD	Pediatric	Allelic with Limb-girdle muscular dystrophy, 1A (AD); Myopathy, spheroid body (AD)	Cardiovascular; Musculoskeletal; Neurologic	Cardiovascular		Individuals typically present with slowly progressive weakness, and a significant proportion of individuals demonstrate cardiomyopathy, such that surveillance for arrhythmia or conduction defects may allow early treatment (eg, pacemaker, ICD, as well as medical treatment with ACE inhibitors and/or beta-blockers); Cardiac transplantation may be necessary in individuals with severe forms of cardiomyopathy	571956; 3275904; 9270668; 10958653; 12428213; 15111675; 16380616; 20301672; 21336781; 21676617 
MYOZ2	1330	51778	Cardiomyopathy, familial hypertrophic, 16	AD	Pediatric		Cardiovascular	Cardiovascular		Surveillance and preventive measures related to cardiac manifestations, which have been reported as including arrhythmias, may allow early diagnosis and medical management as well as pacemaker placement, which may reduce morbidity and mortality	17347475; 19472918 
MYPN	23246	84665	Cardiomyopathy, dilated, 1KK; Cardiomyopathy, familial hypertrophic, 22; Cardiomyopathy, familial restrictive, 4	AD	Pediatric		Cardiovascular	Cardiovascular		Surveillance (eg, including echocardiogram and electrocardiogram) and preventive measures related to cardiac manifestations may allow early diagnosis and  management, which may reduce morbidity and mortality	18006477; 22286171; 22892539
NAA10	18704	8260	N-terminal acetyltransferase deficiency (Ogden syndrome)	XL	Pediatric	Allelic withMicrophthalmia, syndromic I (Lenz microphthalmia) (XL)	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Cardiovascular		Though the overall phenotype may be recognizable, reported individuals have died due to sequelae of arrhythmias, and surveillance and awareness may allow early diagnosis and treatment, which may reduce morbidity and mortality	11426460; 21700266; 24431331
NADK2	26404	133686	2,4-dienoyl-CoA reductase deficiency	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24847004
NAGA	7631	4668	Kanzaki disease; Alpha-n-acetylgalactosaminidase deficiency; Schindler disease type I; Schindler disease type III	AR	N/A	N/A	Biochemical; Dermatologic; Neurologic 	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2564952; 2243144; 7707696; 8071745; 8040340; 8782044; 11313741; 11251574; 14685826; 15619430 
NAGLU	7632	4669	Mucopolysaccharidosis type IIIB (Sanfilippo syndrome B)	AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic	General	BMT has been reported as beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4261742; 3118713; 1606713; 1293388; 8650226; 3118713; 11068184; 12202988; 15933803; 18218046; 20852935; 21937992; 21712855; 22976768 
NAGS	17996	162417	N-acetylglutamate synthase deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		The condition may manifest with severe neurological sequelae secondary to the accumulation of ammonia, and medical treatment both in the acute and chronic setting (eg, with N-carabamylglutamate) can be effective	7453791; 3139931; 2373115; 1405478; 7623444; 9877039; 10626533; 12594532; 17421020; 17510757; 19533169; 20301396; 21941437; 22594780; 23776373
NALCN	19082	259232	Neuroaxonal neurodegeneration, infantile, with facial dysmophism	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12558119; 23749988
NANOS1	23044	340719	Spermatogenic failure 12	AD	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23315541
NAT1	7645	9	Acetylation, NAT1-related	AD	Pediatric	 	Biochemical	Pharmacogenomic		Medication dosage/selection may be affected related to multiple agents, including isoniazid, hydralazine, phenytoin, procainamide, and some sulfa drugs	17909564; 21878835 
NAT2	7646	10	Acetylation, NAT2-related	AD	Pediatric	 	Biochemical	Pharmacogenomic		Variants may have pharmacogenomic importance, as medication dosage/selection may be affected related to multiple agents, including isoniazid, hydralazine, phenytoin, procainamide, and some sulfa drugs	13820968; 14164493; 5414058; 871863; 913027; 7378086; 3707628; 3712391; 3778197; 3815349; 1968463; 2068113; 8102597; 7920692; 7668286; 8637343; 9918135; 9660060; 12654968; 16416399; 19379125; 19891553; 20485159; 20602614; 20860460; 20941486; 22092036 
NAT8L	26742	339983	N-acetylaspartate deficiency	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11310630; 15328569; 16802720; 19807691 
NBAS	15625	51594	Short stature, optic nerve atrophy, and Pelger-Huet anomaly (SOPH syndrome)	AR	N/A	N/A	Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20577004
NBEAL2	31928	23218	Gray platelet syndrome	AR	Pediatric		Hematologic	Hematologic		Individuals may manifest with anemia (sometimes requiring RBC transfusions) due to bleeding tendencies, and preventive measures and treatment (eg, when surgery is needed) may be beneficial; Recognition of the development of myelofibrosis may also be beneficial in order to allow prompt management	5129551; 6156948; 3414674; 8192152; 20709904; 21765411; 21765412; 21765413; 23100277 
NBN	7652	4683	Breast cancer, susceptibility to; Nijmegen breakage syndrome	AD/AR	Pediatric (Nijmegen breakage syndrome); Adult (Breast cancer, susceptibility to)		Allergy/Immunology/Infectious; Hematologic; Musculoskeletal; Neurologic; Oncologic	Allergy/Immunology/Infectious; Hematologic; Oncologic	Variants may result in increased risk of a number of malignancies, including acute lymphoblastic leukemia	In Breast cancer, susceptibility to, awareness may allow surveillance, preventive measures, and early recognition and treatment of disease; Nijmegen breakage syndrome may be recognizable, but surveillance for cancer may be beneficial, and specific treatment modalities may be preferable (eg, cytostatics are first-line, radiomimetics and radiation therapy should be avoided, and reduced-dose chemotherapy should be used); Surveillance and prompt treatment of hematologic manifestations (eg, aplastic anemia,  bone marrow failure) may be beneficial; Due to immunodeficiency, early and aggressive treatment of infections can be beneficial	3802554; 7545870; 8929954; 9590181; 9590180; 15474156; 15338273; 16634478; 16033915; 20143155; 21166880; 21799032; 21700777; 20143155; 21656575; 22006311; 22070649; 22114071; 22373003; 22491912; 22864661
NCF1	7660	653361	Chronic granulomatous disease, autosomal recessive, cytochrome b-positive, type I	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Surveillance for infections and infectious complications is indicatred, and preventive measures (eg, antibacterial/antifungal prophylaxis, interferon gamma) may be beneficial; To treat fungal infections, specific antifungal drugs may be beneficial, and longer treatment courses (as well as specific considerations including coadministration with corticosteroids) may be indicated in individuals with CGD; In some instances, HSCT may be beneficial; Certain agents should be avoided, including material that would allow fungal spore inhalation	5755008; 6848934; 3011845; 3339133; 2770793; 2011585; 11060536; 10706888; 11133775; 16972229; 19329991; 22157170; 22876374; 22924696
NCF2	7661	4688	Chronic granulomatous disease, autosomal recessive, cytochrome b-positive, type II	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Surveillance for infections and infectious complications is indicatred, and preventive measures (eg, antibacterial/antifungal prophylaxis, interferon gamma) may be beneficial; To treat fungal infections, specific antifungal drugs may be beneficial, and longer treatment courses (as well as specific considerations including coadministration with corticosteroids) may be indicated in individuals with CGD; In some instances, HSCT may be beneficial; Certain agents should be avoided, including material that would allow fungal spore inhalation	2770793; 7795241; 10498624; 11060536; 22157170; 22876374; 23264412
NCF4	7662	4689	Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Surveillance for infections and infectious complications is indicatred, and preventive measures (eg, antibacterial/antifungal prophylaxis, interferon gamma) may be beneficial; To treat fungal infections, specific antifungal drugs may be beneficial, and longer treatment courses (as well as specific considerations including coadministration with corticosteroids) may be indicated in individuals with CGD; In some instances, HSCT may be beneficial; Certain agents should be avoided, including material that would allow fungal spore inhalation	19692703; 22157170; 22876374
NCSTN	17091	23385	Acne inversa, familial 1	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20929727; 22622421
NDE1	17619	54820	Lissencephaly 4; Microhydranencephaly	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10762554; 21529751; 21529752; 22526350
NDP	7678	4693	Norrie disease; Exudative vitreoretinopathy, 2, X-linked 	XL	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	95062; 1303235; 1307245; 1642288; 8252044; 8457509; 8110678; 7662640; 7814011; 7795608; 7627181; 8990009; 17325173; 17334993; 20301506; 20491809; 20679667; 21179243; 21960066; 22563645; 22674248 
NDRG1	7679	10397	Charcot-Marie-Tooth disease, type 4D	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10831399; 22978647; 23163601
NDST1	7680	3340	Mental retardation, autosomal recessive 46	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21937992; 25125150
NDUFA1	7683	4694	Mitochondrial complex I deficiency	XL	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 17262856; 21596602
NDUFA10	7684	4705	Mitochondrial complex I deficiency; Leigh syndrome	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 21150889
NDUFA11	20371	126328	Mitochondrial complex I deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 18306244
NDUFA12	23987	55967	Mitochondrial complex I deficiency; Leigh syndrome	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21617257
NDUFA13	17194	51079	Thyroid carcinoma, Hurthle cell	AD	Adult		Oncologic	Oncologic	Only 1 individual has been reported 	Surveillance and/or awareness of thyroid cancer risk may allow early diagnosis and treatment of neoplasms, which may improve outcomes	15841082
NDUFA2	7685	4695	Mitochondrial complex I deficiency; Leigh syndrome	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 18513682
NDUFA9	7693	4704	Mitochondrial complex I deficiency; Leigh syndrome	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22114105
NDUFAF1	18828	51103	Mitochondrial complex I deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 17557076; 21931170
NDUFAF2	28086	91942	Mitochondrial complex I deficiency; Leigh syndrome	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 16200211; 20571988; 20818383
NDUFAF3	29918	25915	Mitochondrial complex I deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 19463981
NDUFAF4	21034	29078	Mitochondrial complex I deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 18179882
NDUFAF5	15899	79133	Mitochondrial complex I deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 18940309; 19542079; 21607760 
NDUFAF6	28625	137682	Mitochondrial complex I deficiency; Leigh syndrome	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18614015
NDUFB3	7698	4709	Mitochondrial complex I deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 15534765; 22277967
NDUFS1	7707	4719	Mitochondrial complex I deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 11349233; 15824269; 16478720; 20382551; 21203893 
NDUFS2	7708	4720	Mitochondrial complex I deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 11220739; 20819849; 22036843 
NDUFS3	7710	4722	Mitochondrial complex I deficiency; Leigh syndrome	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 14729820; 22499348 
NDUFS4	7711	4724	Mitochondrial complex I deficiency; Leigh syndrome	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9463323; 10944442; 11743516; 11181577; 12616398; 16478720; 19107570; 19364667; 22326555 
NDUFS6	7713	4726	Mitochondrial complex I deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 15372108; 19259137
NDUFS7	7714	374291	Mitochondrial complex I deficiency; Leigh syndrome	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10330338; 11743516; 17275378; 17604671 
NDUFS8	7715	4728	Mitochondrial complex I deficiency; Leigh syndrome	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9837812; 11743516; 15159508
NDUFV1	7716	4723	Mitochondrial complex I deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10080174; 11743516; 18991197; 21696386 
NDUFV2	7717	4729	Mitochondrial complex I deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 12754703; 21548921 
NEB	7720	4703	Nemaline myopathy 2	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10051637; 10619714; 12207937; 15221447; 16917880; 19232495; 19805734; 21798101; 22367672; 23010307
NECAP1	24539	25977	Epileptic encephalopathy, early infantile 21	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24399846
NEFL	7739	4747	Charcot-Marie-Tooth disease, axonal, type 2E	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10841809; 12481988; 15111691; 16619203; 17620486; 18758688; 19158810; 19286384; 20039262; 20301366; 22206013
NEK1	7744	4750	Short-rib thoracic dysplasia 6 with or without polydactyly	AR/Digenic	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal; Renal	General	Heterozygous (digenic) mutations in both NEK1 and DYNC2H1 can result in disease	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21211617; 22499340; 22795106; 22499340
NEK2	7745	4751	Retinitis pigmentosa 67	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24043777
NEK8	13387	284086	Nephronophthisis 9	AR	N/A	N/A	Cardiovascular; Gastrointestinal; Renal	General	While individuals were first described with having cystic kidneys, later reports included cysts affecting other organs, such as the liver and pancreas, as well as cardiac disease	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18199800; 23418306
NEU1	7758	4758	Sialidosis, type I; Sialidosis, type II	AR	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic ; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	610425; 610423; 107795; 6777097; 6839532; 3742847; 8985184; 9054950; 11063730; 11829139; 14695530; 15908988; 19568825 
NEUROG3	13806	50674	Diarrhea 4, malabsorptive, congenital	AR	Pediatric		Endocrine; Gastrointestinal	Gastrointestinal		Individuals may present in infancy with severe hyperchloremic metabolic acidosis  due to vomiting and diarrhea, and may require parenteral nutrition and limited enteral feeding (with oral vitamins and electrolyte supplementation); Surveillance may allow early recognition and treatment of diabetes mellitus (including with insulin); One reported individual required liver/intestinal transplant	16855267; 21490072 
NEXN	29557	91624	Cardiomyopathy, familial hypertrophic, 20; Cardiomyopathy, dilated, 1CC	AD	Pediatric		Cardiovascular	Cardiovascular		Surveillance (eg, including echocardiogram/electocardiogram) and preventive measures, including medical management, may reduce morbidity and severe sequelae such as sudden cardiac death; Cardiac transplantation has ben reported	19881492; 20970104
NF1	7765	4763	Neurofibromatosis type 1, Neurofibromatosis-Noonan syndrome; Watson syndrome	AD	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic	Cardiovascular; Oncologic; Ophthalmologic	The condition can involve multiple organ systems affected by neoplastic and other complications that would warrant intervention	As clinical diagnosis can be challenging early, and  optic pathway gliomas affect approximately 15% of people with NF1 (a minority can cause blindness), children should undergo surveillance by a pediatric ophthalmologist to screen for evidence of optic nerve damage from an occult optic nerve glioma; Surveillance for other manifestations and their sequelae, such as cardiovacular anomalies, may also be beneficial; Awareness of the risk of malignancy (in addition to benign neurofibromas and optic gliomas, NF1 includes a risk of brain tumors, and malignant peripheral nerve sheath tumors, as well as hematologic malignancies) may allow prompt detection and management	6798841; 14050005; 6025371; 4965691; 4633999; 1131001; 6777096; 6786260; 6814376; 6417335; 6422759; 3083645; 3083258; 2897130; 2510517; 2134734; 1770531; 1909491; 1719426; 1302608; 8317503; 7931405; 7874161; 7477989; 7502979; 8644707; 9128932; 9126041; 9529361; 10204844; 10480204; 10699117; 10951462; 11078559; 11041400; 11292406; 11298367; 11704931; 11453810; 11176707; 11296017; 11283797; 12011145; 12180143; 12089128; 12707950; 12588224; 12566521; 15019338; 16380919; 15690406; 16787982; 17105749; 17362838; 17327286; 17932395; 19845691; 19449407; 19117870; 20301288; 22934576; 22943186; 22961690; 22965642; 22965773; 23047517; 23047742; 23060584; 23071069; 23099008; 23696535 23812910
NF2	7773	4771	Neurofibromatosis type II; Schwannomatosis 2	AD	Pediatric		Oncologic	Oncologic		In order to detect neoplasms (individuals are predisposed to a variety of types of central nervous system tumors), surveillance with regular cranial MRI is indicated, which may allow detection and treatment; In the treatment of neoplasms, radiation therapy should be avoided (especially in childhood) due to the risk of causing or accelerating other neoplasms 	5304294; 4990044; 1479599; 1479598; 8379998; 7913580; 7747758; 8188242; 8751853; 8755919; 9399891; 9643284; 9811917; 9817927; 9863591; 10569966; 10220142; 9874852; 10771486; 11159946; 11342693; 11425952; 12136076; 12235555; 12473765; 12011146; 12566519; 15190457; 15235024; 15831594; 15994874; 16341811; 16521120; 16534111; 16983642; 19476995; 19880713; 20301380; 21451418; 21358190; 22038540; 22098617; 22929112; 22931905; 22989157; 23682341; 23921933; 23931824; 23939548
NFIX	7788	4784	Marshall-Smithsyndrome; Sotos syndrome 2	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic; Pulmonary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20673863; 22301465; 22982744 
NFKB2	7795	4791	Immunodeficiency, common variable, 10	AD	Pediatric		Allergy/Immunology/Infectious; Endocrine	Allergy/Immunology/Infectious; Endocrine		Individuals have been described with immunodeficiency and recurrent infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Central adrenal insufficiency has been described, and medical management (with glucocorticoid and mineralocorticoid replacement) has been described as beneficial	24140114; 24888602
NFKBIA	7797	4792	Ectodermal dysplasia, anhidrotic, with T-cell immunodeficiency	AD	Pediatric		Allergy/Immunology/Infectious; Dental; Dermatologic; Gastrointestinal	Allergy/Immunology/Infectious	Syndromic features may not be clinically recognizable prior to infectious manifestations	In addition to ectodermal manifestations, individuals have immunodeficiency, and surveillance/prophylaxis/aggressive treatments of infection may be beneficial; BMT has been reported as effective	14523047; 15337789; 16769798; 17931563; 18412279
NFU1	16287	27247	Multiple mitochondrial dysfunctions syndrome 1	AR	N/A	N/A	Biochemical; Cardiovascular; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11156534; 21944046
NGF	7808	4803	Neuropathy, hereditary sensory and autonomic, type V	AR	N/A	N/A	Neurologic	General	Insensivity to pain may result in injuries and infections	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14976160; 20978020
NGLY1	17646	55768	Congenital disorder of glycosylation, type Iv	AR	Pediatric		Biochemical; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	22581936; 24651605
NHEJ1	25737	79840	Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation	AR	Pediatric		Allergy/Immunology/Infectious; Craniofacial; Musculoskeletal; Neurologic	Allergy/Immunology/Infectious	Some individuals may not demonstrate obvious dysmorphic features	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	12604777; 16439204; 16439205; 17191205; 20597108 
NHLRC1	21576	378884	Epilepsy, progressive myoclonic 2B (Lafora)	AR	N/A	N/A	Neurologic	General	While antiepileptic drugs may be effective, certain medications (eg, phenytoin, and possibly carbamazepine, oxcarbazepine, and lamotrigine) can exacerbate myoclonus	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10513696; 14663053; 12958597; 15781812; 16021330; 16356781; 16950819; 19267391; 20301563
NHP2	14377	55651	Dyskeratosis congenita, autosomal recessive 2	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic;  Oncologic; Pulmonary	Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary		Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; Lung transplant may be indicated in individuals with advanced lung diease; HSCT may be indicated due to manifestations including leukemia and bone marrow failure (which may also be treated with androgen therapy), but the long-term efficacy may not be optimal	18523010; 20301779
NHS	7820	4810	Nance-Horan syndrome; Cataract 40	XL	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4470901; 458526; 11836358; 14564667; 15623749; 16736028; 17256798; 19414485; 20882036
NIN	14906	51199	Seckel syndrome 7	AR	N/A	N/A	Craniofacial; Endocrine; Musculoskeletal; Neurologic	Endocrine		The condition can include manifestations including endocrine anomalies (eg, hypothyroidism, hypogonadism), some of which may respond to appropriate hormonal therapy (eg, thyroid hormone replacemetn therapy, estrogen therapy)	22933543
NIPA1	17043	123606	Spastic paraplegia 6	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7854534; 14508710; 15711826; 21419568; 21599812; 22302102 
NIPAL4	28018	348938	Ichthyosis, congenital, autosomal recessive	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15317751; 17557927; 20301593 
NIPBL	28862	25836	Cornelia de Lange syndrome 1	AD	N/A	N/A	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Renal	General	Somatic mosaicism is relatively frequent	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2246693; 2333897; 8291513; 8281279; 8291537; 8291518; 9279756; 12784293; 15146185; 15146186; 15633188; 16236812; 16770807; 17661813; 20301283; 20358602; 20583156; 22241092; 22581668; 22676896; 22965847; 23254390; 23304577; 23313159; 23505322
NKX2-1	11825	7080	Choreoathetosis, hypothyroidism, and neonatal respiratory distress	AD	Pediatric	Allelic with Chorea, hereditary benign (AD)	Allergy/Immunology/Infectious; Endocrine; Neurologic; Pulmonary	Allergy/Immunology/Infectious; Endocrine; Neurologic; Pulmonary		Individuals may have congenital hypothyroidism necessitating thyroxine replacement; Response to levodopa has also been reported; Neonates may require ventilatory support, and may be prone to recurrent respiratory infections, and awareness may allow prophylactic measures, as well as prompt and aggressive treatment of infections	9565498; 10931427; 11854319; 11854318; 11971878; 12891678; 15289765; 15955952; 19336474; 22488412; 22825795 
NKX2-5	2488	1482	Atrial septal defect 7, with or without AV conduction defects; Hypothyroidism, congenital nongoitrous, 5	AD	Pediatric	Mutations may also result in a variety of congenital heart malformations: Hypoplastic left heart syndrome 2 (AD); Ventricular septal defect 3 (AD); Conotruncal heart malformations, variable (AD); Tetralogy of Fallot (AD)	Cardiovascular; Endocrine	Cardiovascular; Endocrine		Individuals may have arrhythmias as well as congenital cardiac malformations (and can have arrhthymias without obvious structural cardiac malformations), and surveillance and treatment may be beneficial; In Hypothyroidism, congenital nongoitrous, medical treatment for thyroid insufficiency may be effective, and individuals may also be at risk for cardiac anomalies	1260978; 9651244; 10587520; 11714651; 12414819; 14607454; 15810002; 16418214; 16896344; 20659440; 21110066; 19948535; 20456451; 21637914
NKX2-6	32940	137814	Persistent truncus arteriosus	AR	N/A	N/A	Cardiovascular	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15649947
NKX3-2	951	579	Spondylo-megaepiphyseal-metaphyseal dysplasia	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3925497; 13680008; 20004766
NLGN3	14289	54413	Asperger syndrome, X-linked 1; Autism, X-linked 1	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12669065
NLGN4X	14287	57502	Asperger syndrome, X-linked 2; Autism, X-linked 2; Mental retardation, X-linked	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12669065; 14963808; 18231125; 19645625; 19726642 
NLRC4	16412	58484	Autoinflammation with infantile enterocolitis (AIFEC);  Familial cold autoinflammatory syndrome 4	AD	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		In Autoinflammation with infantile enterocolitis, individuals present with recurrent autoinflammatory manifestations in infancy, and treatment with IL1R antagonists has been described as beneficial (decreased frequency of flares, corticosteroid requirements, and clinical and lab severity); In Familial cold autoinflammatory syndrome 4, manifestations frequently resolve without treatments, though analgesics may be helpful related to joint pain	25217959; 25217960; 25385754
NLRP1	14374	22861	Corneal intraepithelial dyskeratosis and ectodermal dysplasia	AD	N/A	N/A	Dermatologic; Musculoskeletal; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23349227
NLRP12	22938	91662	Familial cold autoinflammatory syndrome 2 	AD	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Treatment with colchicine has been reported as effective in reducing fever	18230725; 22753383
NLRP3	16400	114548	Chronic Infantile Neurologic Cutaneous Articular (CINCA) syndrome; Neonatal Onset Multisystem Inflammatory Disease (NOMID); Muckle-Wells syndrome	AD	Pediatric	Allelic with Familial cold-induced autoinflammatory syndrome 1 (AD)	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dermatologic; Renal	Allergy/Immunology/Infectious		Individuals may present with autoinflammatory manifestions, which can be severe, progressive, and ultimately fatal, medical treatment with IL1R antagonists (eg, anakinra, canakinumab) has been described as an effective treatment	14476827; 5769632; 5173311; 49161; 447320; 11687797; 12032915; 12483741; 11992256; 12928894; 16532456; 21356079; 21538043; 21859692; 21967869; 22193915; 22723549 
NLRP7	22947	199713	Hydatidiform mole	AR	Pediatric		Obstetric; Oncologic	Obstetric; Oncologic		Women are likely to have pregnancies with hydatidiform moles, with a high risk of persistent trophoblastic disease, including requiring  chemotherapeutic treatment, and awareness may allow reproductive planning and/or surveillance measures, which may allow early detection and treatment	16874523; 16462743; 19066229; 19246479; 22315435; 22770628 
NME8	16473	51314	Ciliary dyskinesia, primary, 6	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	17360648; 20301301
NNT	7863	23530	Glucocorticoid deficiency 4	AR	Pediatric		Endocrine	Endocrine		Recognition may allow preventive/treatment measures related to adrenal insufficiency	22634753
NOBOX	22448	135935	Premature ovarian failure 5	AD	Pediatric		Endocrine; Obstetric	Obstetric		Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency	17701902
NOD2	5331	64127	Blau syndrome; Sarcoidosis, early-onset	AD/AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Musculoskeletal; Ophthalmologic; Pulmonary	Allergy/Immunology/Infectious		Bi-allelic mutations result in a ~40-fold higher relative risk of Crohn disease; In Blau syndrome, individuals have been described as responding to TNF-alpha or IL1B inhibitory medications	4056967; 3993660; 8394645; 8882056; 9508240; 11385576; 11528384; 12879366 ; 15086578; 15459013; 17698784; 17804789 ; 21788900; 21914217; 21951874; 22147245; 22509093; 22821420; 22859352; 23124805 
NODAL	7865	4838	Heterotaxy, visceral, 5	AD	N/A	N/A	Cardiovascular; Gastrointestinal; Pulmonary; Renal	General	The condition can involve multiple congenital anomalies; Cardiac transplantation has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19064609
NOG	7866	9241	Brachydactyly, type B2; Tarsal-carpal coalition syndrome; Multiple synostosis syndrome 1; Symphalangism, proximal; Stapes ankylosis with broad thumb and toes (Teunissen-Cremers syndrome)	AD	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal	Audiologic/Otolaryngologic	Some conditions may be frequently recognizable based on clinical manifestations	Hearing impairment may be prelingual in some individuals, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	7245852; 6638061; 4019538; 10080184; 10069712; 11545688;  1846737; 12089654; 15770128; 16532400; 17668388; 18440889; 20503332; 19471170; 20503332; 21358557; 21538686; 22855651 
NOL3	7869	8996	Myoclonus, familial cortical	AD	N/A	N/A	Neurologic	General	The condition may be exacerbated by alcohol, and alleviated by medical treatment (eg, with clonazepam)	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22926851
NOP10	14378	55505	Dyskeratosis congenita, autosomal recessive 1	AR	Pediatric		Allergy/Immunology/Infectious; Dental; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic;  Oncologic; Pulmonary	Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary		Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; Lung transplant may be indicated in individuals with advanced lung diease; HSCT may be indicated due to manifestations including leukemia and bone marrow failure (which may also be treated with androgen therapy), but the long-term efficacy may not be optimal	17507419; 20301779
NOP56	15911	10528	Spinocerebellar ataxia 36	AD 	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21683323; 22744658; 22492559
NOTCH1	7881	4851	Aortic valve disease	AD	Pediatric	Allelic with Adams-Oliver syndrome 5 (AD)	Cardiovascular; Dermatologic; Musculoskeletal	Cardiovascular	Variants in some affected individuals were also found in apparently unaffected parents	Individuals may have a variety of cardiovascular malformations, and early diagnosis and treatment (including surgical treatment in some individuals) may reduce morbidity and mortality	16025100; 18593716; 21785343; 22307742; 23102684; 23578328; 25132448
NOTCH2	7882	4853	Alagille syndrome 2	AD	Pediatric	Allelic with Hajdu-Cheney syndrome (AD); Serpentine fibula-polycystic kidney syndrome (AD)	Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Cardiovascular; Gastrointestinal; Renal		The condition may not be clinically apparent; for hepatic complications, medications (eg, ursodeoxycholic acid, cholestyramine), and, when necessary, partial external biliary diversion may be beneficial; other treatments, such as fat-soluble vitamin supplementation may be beneficial; Surveillance for other manifestations, including cardiac and renal manifestations (such as renal tubular acidosis, which has been described in affected individuals), may be beneficial in order to allow early diagnosis and treatment and/or preventive measures	18918373; 14303950; 8723560; 11343321; 16773578; 17159511; 20301450; 21378989; 21681853; 21378985; 21712856; 21793104; 21934706; 22209762; 22488849; 23117206; 23389697; 23401378; 23566664; 24265536
NOTCH3	7883	4854	Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy	AD	Pediatric		Cardiovascular; Neurologic	General; Pharmacogenomic		Certain agents (eg, angiography, anticoagulants, thrombolytic therapy) should be avoided; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7486874; 7564728; 7654071; 7500094; 8878478; 9818928; 10371078; 12136071; 15210914; 15313839; 15378071; 15096408; 16009764; 16263847; 15851739; 17135568; 16717210; 16864835; 18765654; 19174371; 20038773; 20301673; 22218279; 22996955; 23025651 
NPC1	7897	4864	Niemann-Pick disease, type C1; Niemann-Pick disease, type D 	AR	N/A	N/A	Biochemical; Gastrointestinal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3865225; 3378364; 9211849; 9245994; 9634529; 9512307; 10361985; 10480349; 11182931; 12555942; 12408188; 15596783; 12955717; 15465421; 15465428; 16098014; 17497724; 17689147; 20301473; 19206179; 20484681
NPC1L1	7898	29881	Ezetimibe, nonresponse to	AD/AR	Pediatric		General	Pharmacogenomic		Variants may have pharmacogenomic relevance, as in patients with mutations, medication choice might be altered	15679830; 20686565
NPC2	14537	10577	Niemann-pick disease, type C2	AR	N/A	N/A	Biochemical; Gastrointestinal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; BMT has been described	8554047; 11125141; 11567215; 12447927; 17470133; 20301473; 20393800 
NPHP1	7905	4867	Joubert syndrome 4; Senior-Loken syndrome 1; Nephronophthisis 1	AR	N/A	N/A	Hematologic; Neurologic; Ophthalmologic; Renal	General	The conditions may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Renal transplant has been described, though nephrotic syndrome may recur post-transplantation	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14823504; 13763238; 13910672; 9326933; 9361039; 9856524; 10196704; 15138899; 16155189; 16571882; 20301500; 20454808; 20652329; 21068128; 21258817; 21866095; 23559409
NPHP3	7907	27031	Nephronophthisis 3; Meckel syndrome 7; Renal-hepatic-pancreatic dysplasia 	AR	N/A	N/A	Gastrointestinal; Hematologic; Musculoskeletal; Renal	General	Liver-kidney transplantation has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8874114; 12872122; 18371931; 19303681; 19177160; 20007846; 21068128; 21642631;21866095 
NPHP4	19104	261734	Nephronophthisis 4; Senior-Loken syndrome 4	AR	N/A	N/A	Ophthalmologic; Renal	General	Avoidance of certain medications (eg, nephrotoxic agents) may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12205563; 11920287; 12244321; 21068128; 21866095 
NPHS1	7908	4868	Nephrotic syndrome, type 1	AR	N/A	N/A	Renal	General	Medical therapy to control bacterial infections, along with renal transplantation, can be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6384451; 9660941; 10577936;  17413422; 17290294; 20650908; 20798252; 21125408; 22009864; 22565185; 22584503; 22653594 
NPHS2	13394	7827	Nephrotic syndrome, type 2	AR	N/A	N/A	Renal	General	The disease is steroid resistant; Partially steroid-responsive AD forms have been described; Renal transplant has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8589695; 8606597; 10742096; 11729243; 12464671; 12707396; 17109732; 22036940; 22080622; 22228437; 22565185; 23013956 
NPPA	7939	4878	Atrial fibrillation, familial, 6; Atrial standstill 2	AD/AR	Adult		Cardiovascular	Cardiovascular	The clinical onset of manifestations has been described in the adult period, but earlier surveillance may be beneficial	Surveillance, preventive measures, and early medical intervention to prevent morbidity related to arrhthymias (atrial standstill/atrial fibrillation, depending on the inheritance pattern) may be beneficial	6225642; 18614783; 20064500; 20543198; 23275345
NPR2	7944	4882	Epiphyseal chondrodysplasia, Miura type; Acromesomelic dysplasia, Maroteaux type	AD/AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15146390; 22691581; 22870295; 24057292; 24259409
NR0B1	7960	190	Adrenal hypoplasia, congenital; 46,XY sex reversal 2 	XL	Pediatric		Endocrine; Genitourinary; Obstetric; Oncologic	Endocrine; Genitourinary; Obstetric; Oncologic	Digenic inheritance (with GNRH1) has been reported; Dosage-sensitive sex reversal has been described due to duplications	Affected individuals typically present in infancy with acute-onset adrenal insufficiency, which can be lethal, and preventive and treatment measures can be effective; In individuals with hypogonadotropic hypogonadism, testosterone may be required to induce puberty;  Surgical interventions may decrease the risk of gonadal tumors 	6891556; 7951319; 7990958; 9003500; 9529340; 10022408; 11549627; 11788621; 12519885; 17503084; 17164309; 20301604; 20301714; 21408189; 21632081; 21739173; 21925982; 22456342; 22570964 
NR2E3	7974	10002	Enhanced S-cone syndrome; Retinitis pigmentosa 37	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13553271; 11071390; 10655056; 15229190; 17564971; 18294254; 20212206; 21364904; 22605927; 22807301 
NR2F1	7975	7025	Bosch-Boonstra optic atrophy syndrome	AD	N/A	N/A	Craniofacial; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24462372
NR2F2	7976	7026	Congenital heart defects 4	AD	N/A	N/A	Cardiovascular	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18371933; 24702954
NR3C1	7978	2908	Glucocorticoid resistance	AD/AR	Pediatric		Endocrine	Endocrine		Treatment focuses on suppression of excess ACTH production, and may include high-dose mineralocorticoid-sparing synthetic glucocorticoids; Individuals may also display other endocrinologic anomalies (eg, growth hormone deficiency), and surveillance and prompt recognition and treatment may be beneficial	186477; 6841559; 2996089; 1704018; 8445027; 8863343; 11701741; 11589680; 11932321; 12050230; 12754700; 14764810; 15769988; 16449337; 17635946; 18319312; 19694013; 19933394; 23076843 
NR3C2	7979	4306	Pseudohypoaldosteronism type I, autosomal dominant; Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy	AD	Pediatric		Obstetric; Renal	Obstetric; Pharmacogenomic; Renal		In Pseudohypoaldosteronism type I, autosomal dominant Although the disorder may eventually become asymptomatic, individuals can present with neonatal salt wasting, and prompt recognition and treatment of electrolyte imbalances (eg, with sodium supplementation) can be beneficial; In Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy, hypertension can be severe, and present relatively early in life, and additionally may be exacerbated in pregnancy, and may be accompanied by findings such as hypokalemia, and may necessitate interventions including delivery; It has been suggested the spironolactone is contraindicated	1939532; 9662404; 10884226; 11134129; 11344206; 12788847; 16954160; 16972228; 20453518; 21159846; 21903996; 21932599 
NR5A1	7983	2516	Adrenocortical insufficiency; 46, XY sex reversal, 3; Premature ovarian failure 7	AD/AR	Pediatric	Allelic with Spermatogenic failure 8 (AD)	Endocrine; Genitourinary; Obstetric; Oncologic	Endocrine; Genitourinary; Obstetric; Oncologic		In adrenocortical insufficiency, which can manifest with severe electrolyte abnormalities and neurologic sequelae, recognition may allow beneficial medical management (eg, with hydrocortisone, fludrocortisone); In 46, XY sex reversal, surgical removal of abdominal dysgenetic gonads and streak gonads is indicated due to increased risk of  tumors, and it has been suggested that early sperm cryopreservation may be beneficial for males to allow reproduction; Hormone replacement therapy may be beneficial in puberty; In Premature ovarian failure 7, genetic knowledge may be beneficial to allow Interventions such as preserving eggs in women with premature ovarian insufficiency	1956279; 10369247; 11038323; 11932325; 15070943; 15579739; 15472171; 16439367; 16684822; 17200175; 17694559; 19246354; 19318730; 19439508; 19849982; 20301714; 20453312; 20861607; 20887963; 21163476; 21535007; 21654157; 21691975; 22028768; 22080441; 22474171; 22549935; 22907560; 22909003; 23044873; 23095176; 23096908; 23153500; 23168057; 23299922; 23543655; 24067197; 24073220; 24157186; 24231572
NRAS	7989	4893	Autoimmune lymphoproliferative syndrome type IV; Noonan syndrome 6	AD	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic; Oncologic	Cardiovascular; Oncologic	Noonan syndrome may include multiple congenital anomalies	 The condition may also include cardiac anomalies and dysrhythmias, and appropriate care may be beneficial; Individuals with Autoimmune lymphoproliferative syndrome type IV may be at risk of hematologic malignancies, and individuals with Noonan syndrome 6 have been described with juvenile myelomonocytic leukemia such that surveillance/early treatment may reduce morbidity	17517660; 19775298; 19966803; 20301303; 21901340; 22855653; 22887781
NRIP1	8001	8204	Schizophrenia	AD	N/A	N/A	Neurologic	General		Evidence or clinical applicability  is unclear	21743468
NRL	8002	4901	Retinitis pigmentosa 27; Clumped pigmentary retinal degeneration	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10192380; 11039579; 12796249; 15591106; 17335001 
NRXN1	8008	9378	Schizophrenia 17; Pitt-Hopkins-like syndrome 2	AD/AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18369103; 17989066; 18945720; 19896112; 21424692
NSD1	14234	64324	Sotos syndrome; Weaver syndrome; Beckwith-Wiedemann syndrome	AD	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Cardiovascular; Oncologic; Renal	The conditions may include multiple congenital anomalies	While only reported in the minority of individuals, individuals are at increased risk of malignancy, and recognition may allow prompt diagnosis and treatment; Surveillance for cardiac and renal complications may also be beneficial in order to allow prompt recognition and management	14148233; 4366187; 6324572; 3565472; 2319581; 1552397; 10507738; 10434127; 11146472; 11078573; 11813184; 11896389; 12464997; 12525543; 14517949; 14571271; 14997421; 15125616; 16010674; 15452385; 15362962; 15455365; 15365454; 16170239; 15942875; 15852475; 16222665; 16780628; 16329110; 17825104; 17480008; 17420391; 18304174; 19914434; 20101679; 20420030; 21677402; 21738022; 21834047; 22012791; 21342349; 20301652 
NSDHL	13398	50814	Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD syndrome); CK syndrome	XL	N/A	N/A	Cardiovascular; Dermatologic; Musculoskeletal; Pulmonary; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5696317; 7408908; 8882402; 10710233; 10710235; 11907515; 12966526; 19842190; 19377476; 20605772; 21129721; 21290788 
NSMF	29843	26012	Hypogonadotropic hypogonadism 9 with or without anosmia	AD	Pediatric		Endocrine; Neurologic	General	Hormonal treatment may be effective to induce and maintain secondary sex characteristics, as well as to allow reproduction; Syngergistic effects (eg, with FGFR1) have been reported	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15362570; 17235395; 21300340; 21700882; 22035731 
NT5C2	8022	22978	Spastic paraplegia 45	AR	N/A	N/A	Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19415352; 24482476
NT5C3A	17820	51251	Uridine 5-prime monophosphate hydrolase deficiency, hemolytic anemia due to	AR	Pediatric		Hematologic	Hematologic		The condition may manifest with hereditary hemolytic anemia, and transfusions have been reported as necessary (though only infrequently in the described individuals)	4372252; 6317231; 6307548; 3352512; 11369620; 16402212; 17128459; 18499901 
NT5E	8021	4907	Calcification of joints and arteries	AR	N/A	N/A	Cardiovascular; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21288095
NTF4	8024	4909	Glaucoma 1, open angle, O	AD	Adult		Ophthalmologic	Ophthalmologic; Pharmacogenomic		Open-angle glaucoma is typically asymptomatic until  late stages, when irreversible  nerve damage has already taken place; Agents that may contribute to glaucoma should be avoided	19765683; 20215012 
NTRK1	8031	4914	Insensitivity to pain, congenital, with anhidrosis	AR	Pediatric	Allelic with Medullary thyroid carcinoma, familial (AD), but the evidence/clinical applicability is unclear	Allergy/Immunology/Infectious; Neurologic	Allergy/Immunology/Infectious; Neurologic		Individuals may manifest with poor thermoregulation due to anhidrosis, which may result in potentially severe fevers, and awareness can allow measures to help control temperature in order to decrease potential sequelae; Congenital insensitivity to pain can result in injuries, some of which may in theory be preventable with early diagnosis and preventive measures (eg, tooth extraction may be indicated); Recurrent infections have been described, and preventive measures and awareness allowing early diagnosis and aggressive treatmentment of infections may be beneficial	8696348; 10088743; 10861667; 11744315; 12949319; 15534759; 15695606; 16490492; 19618435; 20301726; 19089473; 17915006; 20647579; 21559108; 21708027; 22032467; 22355435; 22653642; 22814739; 22957891; 23112235
NTRK2	8032	4915	Obesity, hyperphagia, and developmental delay	AD	N/A	N/A	Endocrine; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15494731
NUBPL	20278	80224	Mitochondrial complex I deficiency	AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic	General	Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement 	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11743516; 20818383; 23553477
NUP155	8063	9631	Atrial fibrillation 15	AR	Pediatric		Cardiovascular	Cardiovascular		Though described individuals have suffered early morbidity and mortality despite early recognition and management, it is possible that preventive measures (including medical and surgical treatments) may be beneficial related cardiac arrthymias (atrial fibrillation)	15596564; 19070573
NUP62	8066	23636	Striatonigral degeneration, infantile	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3729745; 12374138; 14718703; 16786527
NXF5	8075	55998	Familial heart block and focal segmental glomerulosclerosis	XL	Pediatric	Allelic with Mental retardation, syndromic, X-linked (XL)	Cardiovascular; Neurologic; Renal	Cardiovascular	Renal transplantation has been described; For Mental retardation, syndromic, X-linked, the evidence of mutations as being related to disease causation has been questioned due to subsequent population-based studies	Awareness of the risk of cardiac complications, including progressive heart block, may allow surveillance (eg, with electrocardiogram) and treatment (eg, with pacemaker placement)	11566096; 23686279; 23871722
NYX	8082	60506	Night blindness, congenital stationary, type 1A	XL	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8434607; 9662400; 11062471; 11062472; 16670814; 18617546; 20301423; 20850105; 22183355 
OAT	8091	4942	Gyrate atrophy of choroid and retina	AR	Pediatric		Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	Biochemical		Dietary management (eg, with arginine restriction) may be beneficial	4122112; 572946; 7444439; 7356686; 3339136; 1737786; 11831916; 10604138; 110617919; 1297489; 15750329; 22674428 
OBSL1	29092	23363	Three M syndrome 2	AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19481195
OCA2	8101	4948	Albinism, oculocutaneous, type II; Albinism, brown oculocutaneous; Skin/hair/eye pigmentation 1	AD/AR	N/A	N/A	Dermatologic; Ophthalmologic	General		In Albinism, oculocutaneous, type II; Albinism, brown oculocutaneous, Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Skin/hair/eye pigmentation 1 is a susceptibility factor locus for a multifactorial disease (melanoma)	14904868; 687204; 7920637; 8302318,; 7874125; 7762554; 7887411; 8723691; 10649493; 11179026; 12163334; 14704187; 15889046; 16341609; 17236130; 17952075; 18449927; 18680187; 20861488; 21471978; 21085994; 23103111 
OCLN	8104	100506658	Band-like calcification with simplified gyration and polymicrogyria	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19012351; 19530192; 20727516
OCRL	8108	4952	Dent disease 2; Lowe syndrome	XL	Pediatric		Musculoskeletal; Neurologic; Ophthalmologic; Renal	Pharmacogenomic; Renal		In Dent disease, surveillance and treatment related to manifestations such as hypercalciuria in order to prevent kidney stones, nephrocalcinosis, and to delay the progression of kidney dysfunction may be beneficial (though efficacy is unclear, treatment may include thiazide diuretics, ACE inhibitors, and ARBs); Vitamin D and phosphorous may be beneficial related to skeletal manifestations; Growth hormone may be indicated; Nephrotoxic agents (eg, NSAIDs, aminoglycosides) should be avoided; In Lowe syndrome, which may represent the severe end of of the spectrum of mutation-positive individuals, similar treatment related to renal manifestations may be beneficial, as well as care related to other organ systems	8504307; 9199559; 9632163; 9682219; 199559; 9917791; 10364518; 0923037; 10767176; 15627218; 17162149; 19390221; 21031565 
ODAM	26043	54959	Amelogenesis imperfecta, hypomaturation type, IIA4	AR	N/A	N/A	Dental	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22901946
OFD1	2567	8481	Orofaciodigital syndrome 1; Simpson-Golabi-Behmel syndrome type 2; Joubert syndrome 10; Retinitis pigmentosa 23	XL	N/A	N/A	Craniofacial; Dental; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Pulmonary; Renal	General	The conditions can involve multiple congenital anomalies, as well as, in some individuals, recurrent respiratory infections	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15444577; 13707262; 1248177; 11179005; 16783569; 16397067; 19800048; 20301500; 20301367; 20818665; 21729220; 22353940; 22548404; 22619378; 23033313
OPA1	8140	4976	Glaucoma, normal tension, susceptibility to	AD	Adult	Allelic with Optic atrophy 1 (AD); Optic atrophy with or without deafness (AD); Ophthalmoplegia, myopathy, ataxia, and neuropathy (AD) (in hich deafness has been reported as occuring in early childhood, but is typically later-onset)	Audiologic/Otolaryngologic; Musculoskeletal; Neurologic; Ophthalmologic	Ophthalmologic; Pharmacogenomic	More severely affected individuals with bi-allelic mutations have been described	As IOP is normal and patients usually have good central vision, normal tension glaucoma is underdiagnosed tends to presents late, and genetic knowledge could allow preventive measures and treatment related to vision preservation; Agents that may contribute to glaucoma should be avoided	6493699; 4058877; 11017080; 11017079; 12566046; 15505825; 15531309; 16240368; 15781809; 16158427; 17306754; 18158317; 18496845; 18195150; 18065439; 19029523; 18287570; 19181907; 20417568; 20417570; 20157015; 21621262; 21636302; 20837821; 22776096; 22857269; 22042570; 22382025
OPA3	8142	80207	3-methylglutaconic aciduria, type III; Optic atrophy 3, autosomal dominant	AD/AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2494568; 7510656; 11668429; 12126933; 15342707; 22776096; 24749080
OPHN1	8148	4983	Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance	XL	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9582072; 12807966; 16158428; 16221952; 20528889
OPLAH	8149	26873	5-oxoprolinase deficiency	AR	N/A	N/A	Biochemical; Gastrointestinal; Renal	General	Transient neonatal hypoglycemia has been reported 	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6113726; 6790862; 8127060; 21651516
OPN1LW	9936	5956	Colorblindness, partial, protan series; Blue cone monochromacy; Red cone polymorphism	XL (involving both OPN1 genes)	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2847528; 2788922; 1881435; 1415215; 1302020;  8213841; 8792812;  10982039; 11772996; 12051694; 20579627; 23139274
OPN1MW	4206	2652	Colorblindness, partial, deutan series; Cone dystrophy 5, X-linked; Blue cone monochromacy	XL (involving both OPN1 genes)	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2788922; 1881435; 1302020; 8213841; 8666378; 10982039; 11772996;  15094734; 19421413; 20579627; 23139274 
OPN1SW	1012	611	Tritanopia	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14946611; 1531728
OPTN	17142	10133	Glaucoma, normal tension, susceptibility to; Glaucoma 1, open angle, E 	AD	Adult	Allelic with Amyotrophic lateral sclerosis 12 (AD/AR)	Neurologic; Ophthalmologic	Ophthalmologic; Pharmacogenomic		Open-angle glaucoma is typically asymptomatic until  late stages, when irreversible  nerve damage has already taken place; Agents that may contribute to glaucoma should be avoided	11834836; 17389490; 20428114; 21613650; 21644038; 21730848; 22708870; 22402017; 23062601; 21852022; 21802176 
ORAI1	25896	84876	Immunodeficiency 9	AR	Pediatric	Allelic with Myopathy, tubular aggregate, 2 (AD)	Allergy/Immunology/Infectious; Musculoskeletal; Neurologic	Allergy/Immunology/Infectious		Antiinfectious prophylaxis; early and aggressive treatment of infections	8814256;  15452313; 16582901; 21873530; 24591628
ORC1	8487	4998	Meier-Gorlin syndrome 1	AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	819054; 11477602; 14564153; 21358632; 21358633; 21358631; 22333897 
ORC4	8490	5000	Meier-Gorlin syndrome 2	AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11477602; 21358632; 21358631; 22333897  
ORC6	17151	23594	Meier-Gorlin syndrome 3	AR	N/A	N/A	Craniofacial; Genitourinary; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7710253; 21358632; 22333897
OSMR	8507	9180	Amyloidosis, primary localized cutaneous, 1	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18179886; 19690585
OSTM1	21652	28962	Osteopetrosis, autosomal recessive 5	AR	N/A	N/A	Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	General	HSCT has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3513575; 10325711; 12627228; 15177004; 15108279; 16813530; 17922613; 17985267; 19507210 
OTC	8512	5009	Ornithine transcarbamylase deficiency	XL	Pediatric		Biochemical; Gastrointestinal; Neurologic	Biochemical; Pharmacogenomic	While males are typically severely affected and may require liver transplant (therapy with modalities such as adult derived human liver stem/progenitor cells has also been described), the presentation in females may be more subtle	Treatment to prevent and treat severe sequelae can be beneficial, including prompt recognition and management of acute decompensation (eg, with rapid measures to control hyperammonemia, such as with dialysis, nitrogen scavengers therapy,  appropriate treatment related to catabolism and hydration, and replacement of citrulline/argining); Long-term dietary measures (eg, decreasing the nitrogen load with low protein diet,  use of nitrogen scavengers, and administration of arginine/citrulline) may be beneficial; Certain agents (eg, valproate, haloperidol, and systemic corticosteroids, as well as triggers such as fasting, and physical/psychological stress, with specific considerations during pregnancy to decrease the risk of catabolism) should be avoided due to the potential of adverse events; Hepatic transplant is  considered in individuals (females and males with partial OTC deficiency ) with frequent hyperammonemic episodes	13975632; 6112522; 7351973; 7078580; 7151305; 6427608; 3001312; 2983225; 3945292; 3826955; 3202644; 2843770; 3170748; 1671317; 2342525; 2298453; 1720458; 1549234; 8364586; 8778603; 8786061; 10946359; 11804205; 12063505; 18071043; 20142522; 20301396; 20458665; 20497355; 20817516; 21061009; 21585627; 21642786; 21884343; 21918856; 21926883; 21956151; 22138526; 22232626; 22264779; 22340867; 22507172; 22563224; 22583334; 22594780; 22727265; 22728053; 23209112; 23231960; 23278509; 23283608; 23430866; 23551631; 23568734; 23640148; 23790482; 24006547; 24073003; 24113687; 24142276
OTOA	16378	146183	Deafness, autosomal recessive 22	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	11972037; 19888295
OTOF	8515	9381	Deafness, autosomal recessive 9; Neuropathy, autosomal recessive, 1	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic	Individuals with NSRAN can have normal otoacoustic emissions test, but pure-tone audiometry/ABR will show abnormalities	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	10192385; 12114484; 12525542; 16097006; 16371502; 19461658
OTOG	8516	340990	Deafness, autosomal recessive 18B	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	23122587
OTOGL	26901	283310	Deafness, autosomal recessive 84B	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	23122586
OTX2	8522	5015	Pituitary hormone deficiency, combined 6; Microphthalmia, syndromic 5	AD	Pediatric		Endocrine; Genitourinary; Neurologic; Ophthalmologic	Endocrine; Genitourinary		Hormone replacement therapy can be effective, as individuals may have multiple pituitary insufficiency (eg, manifesting with hypothyroidism, growth hormone, gonadotropin, and cortisol deficiency) 	15846561; 18628516; 18728160; 18781617; 19956411; 18854396; 19965921; 20396904; 20486942; 20494911; 21353197; 22198066 
OXCT1	8527	5019	Succinyl CoA:3-oxoacid CoA transferase deficiency	AR	Pediatric		Biochemical	Biochemical		Diagnosis may allow prompt recognition and treatment of ketoacidotic episodes (eg, with IV glucose and sodium bicarbonate), which may be beneficial to reduce morbidity and mortality	4258782; 1405472; 8751852; 9521962; 10964512; 11286388; 11757586; 20652411 
P2RX2	15459	22953	Deafness, autosomal dominant 41	AD	N/A	N/A	Audiologic/Otolaryngologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12161595; 23345450; 24211385
P2RY12	18124	64805	Bleeding disorder, platelet-type, 8	AD/AR	Pediatric		Hematologic	Hematologic		Affected individuals can have excessive posttraumatic/postsurgical blood loss, as well as life-threatening bleeding episodes, and awareness may allow preventive measures and prompt treatment	1333302; 7706468; 11196645; 12578987; 19229056; 20966167
P3H1	19316	64175	Osteogenesis imperfecta, type VIII	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17277775; 19088120; 22281939; 22608605; 23613367
P3H2	19317	55214	Myopia, high, with cataract and vitreoretinal degeneration	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21885030
PABPN1	8565	8106	Oculopharyngeal muscular dystrophy	AD/AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13997067; 13963574; 9462747; 11712939; 15725589; 15694141; 16648376; 20301305; 21647273; 21742497; 21956377; 22817818 
PACS1	30032	55690	Mental retardation, autosomal dominant 17	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23159249
PAFAH1B1	8574	5048	Lissencephaly 1; Subcortical laminar heterotopia	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9063735; 9817918; 11502906; 11754098; 12621583; 17664403; 18285425; 19050731; 19667223; 20846927; 25140959
PAH	8582	5053	Phenylketonuria; Hyperphenylalaninemia, non-PKU mild	AR	Pediatric		Biochemical; Dermatologic; Neurologic	Biochemical		Dietary measures, including avoidance of aspartame, as well as adjuvant medical therapy, can be effective in preventing severe sequelae, including in preconception/prenatal circumstances	13452670; 5391176; 3008810; 3945244; 2889860; 3308176; 3819940; 2279504; 1361103; 8353710; 7885543; 8828601; 8648535; 9066890; 10472530; 10685924; 10685922; 10636975; 10683054; 11328945; 12555935; 12408183; 11999982; 12501224; 14726806; 15303001; 17935162; 20123473; 20301677; 22669364; 22841515; 22854513; 23062575 
PAK3	8592	5063	Mental retardation, X-linked 30	XL	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8826460; 9332663; 9731525; 10946356; 12884430; 17853471; 18523455
PALB2	26144	79728	Breast cancer; Pancreatic cancer, susceptibility to 3; Fanconi anemia, complementation group N	AD/AR	Pediatric (Fanconi anemia, complementation group N); Adult (Breast cancer, Pancreatic cancer, susceptibility to 3)		Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Renal	Allergy/Immunology/Infectious; Hematologic; Oncologic	The condition may include multiple congenital anomalies	For Fanconi anemia, specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; surveillance for complications such as bone marrow failure is recommended; For pancreatic and breast cancer, surveillance and early treatment may be beneficial	17200668; 17287723; 17200671; 17200672; 19264984; 20858716; 22241545; 20301575; 23448497; 25099575
PANK2	15894	80025	Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration; Neurodegeneration with brain iron accumulation 1  	AD/AR	N/A	N/A	Gastrointestinal; Hematologic; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	477009; 7158329; 3969211; 1447570; 1734303; 7885538; 7898702; 8944032; 11479594; 12058097; 12510040; 14638969; 15911822; 15642932; 16240131; 16437574; 16687521; 18981035; 20301663; 21286947 
PAPSS2	8604	9060	Brachyolmia 4 with mild epiphyseal and metaphyseal changes	AR	N/A	N/A	Endocrine; Musculoskeletal	General	The condition may include endocrinological manifestations such as premature pubarche	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9714015; 9771708; 19474428
PARK2	8607	5071	Parkinson disease 2, autosomal recessive juvenile	AR	N/A	N/A	Neurologic	General	Individuals have been reported as responding to therapies such as levodopa	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9560156; 10894217; 11487568; 11552035; 12056932; 12629236; 12891670; 12730996; 15266615; 15642918; 16130111; 16328510; 17187375; 20182943; 20837857; 20876472; 20558392
PARK7	16369	11315	Parkinson disease 7, autosomal recessive early-onset	AR	N/A	N/A	Neurologic	General	Response to levodopa has been documented	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11462174; 11835383; 12953260; 12446870; 14638971; 16240358; 20837857; 21506293; 22956510 
PAX1	8615	5075	Otofaciocervical syndrome 2	AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	23851939
PAX2	8616	5076	Isolated renal hypoplasia; Papillorenal syndrome	AD	Pediatric	Allelic with  Focal segmental glomerulosclerosis 7 (AD)	Audiologic/Otolaryngologic; Ophthalmologic; Renal	Renal	It has been suggested that mutations may result in isolated renal hypoplasia without other manifestations, though on examination, many individuals have been found to have opthalmalogic anomalies	The disorder may be recognizable in the majority of individuals, but individuals are at risk of renal findings such as unrecognized vesicoureteral reflux, which can cause renal damage, and prophylactic/treatment measures can be beneficial	3377002; 8589702; 7795640; 8588587; 10533062; 11093271; 11730657; 11241473;11297491; 11461952; 20301624; 20358591; 21380624; 22213154
PAX3	8617	5077	Waardenburg syndrome, type 1; Waardenburg syndrome, type 3; Craniofacial-deafness-hand syndrome	AD/AR  	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Musculoskeletal; Ophthalmologic	Audiologic/Otolaryngologic	The condition may be clinically recognizable, especially in individuals with one allelic form, Waardenburg syndrome, type 3, which includes features such as upper limb anomalies; A homozygous individual has been described, with very severe phenotypic effects	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	14902764; 6059431; 091186; 6859126; 1887852; 1347149; 1536170; 1347148; 1576755; 8423616; 8447316; 7981674,; 8588597; 8533800; 7726174; 8664898; 9279758; 9654197; 11683776; 14556253; 12949970; 20024939; 20199465; 20478267; 20664692; 21965087 
PAX4	8618	5078	Diabetes mellitus	AD	N/A	N/A	Endocrine	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14602731; 15509590; 17130187; 16520476; 17426099; 18292467; 21263211 
PAX5	8619	5079	Pre-B cell acute lymphoblastic leukemia	AD	Pediatric		Oncologic	Oncologic		Awareness of B-ALL risk may allow surveillance and early detection and management, which may benefit morbidity and mortality; HSCT has been described	24013638
PAX6	8620	5080	Peters anomaly; Cataract with late-onset corneal dystrophy; Aniridia; Aniridia, cerebellar ataxia, and mental retardation (Gillespie syndrome); Optic nerve hypoplasia; Keratitis; Foveal hypoplasia 1; Coloboma, ocular; Morning glory disc anomaly	AD	Pediatric		Neurologic; Ophthalmologic	Ophthalmologic; Pharmacogenomic	Severe and difficult to treat glaucoma has been reported in many individuals with Peters anomaly; Homozygous/compound heterozygous mutations may cause severe disease, including neuroanatomic anomalies	Individuals with PAX6 related eye anomalies may be recognizable, but some may also be at high risk of developing glaucoma; Agents that may contribute to glaucoma should be avoided	17948455; 14246186; 868970; 1302030; 8364574; 7951315; 8162071; 7550230; 7668281; 8640214; 9138149; 9482572; 9705283; 9931324; 11553050; 11826019; 12325030; 12721955; 15629294; 16543198; 17148041; 17417613; 17595013; 19876904; 22171686; 24290376
PAX8	8622	7849	Hypothyroidism, congenital, nongoitrous 2	AD	Pediatric		Endocrine; Renal	Endocrine	Individuals with genitourinary anomalies possibly associated with the mutation have been described	The untreated condition can result in severe neurological damage, and recognition can allow early medical treatment with thyroid hormone replacement can prevent such sequelae	9590296; 11502839; 11232006; 15356023; 15718293; 20718765; 20857061; 21450989; 21689132; 21976720; 22898500; 23647375
PAX9	8623	5083	Tooth agenesis, selective, 3	AD	N/A	N/A	Dental	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10615120; 11941488; 11827258; 14571272; 16333316; 16479262; 18701815; 19429910; 20485064; 20618716; 21098475; 21443745; 22058014; 22277187; 22747565 
PC	8636	5091	Pyruvate carboxylase deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		In acute episodes, acidosis correction and glucose-containing rehydration are beneficial; Dietary (eg, with high-carbohydrate, low-protein diet, with avoidance of fasting/ketogenic diet) and medical (eg, with supplementation/substrate therapy with citrate, aspartic acid, biotin, triheptanoin) therapy may be beneficial; Liver transplant may be required in some individuals	5771860; 817914; 826106; 6422151; 6424438; 3101494; 1909777; 9585612; 12112657; 16325442; 17403843; 18676167; 19306334; 20301764
PCBD1	8646	5092	Hyperphenylalaninemia, BH4-deficient, D	AR	N/A	N/A	Biochemical	General	Individuals have been treated with phenylalanine restriction and BH4 supplementation, but such interventions may not be indicated	The clinical relevance of the condition is unclear	8352282; 9585615; 9760199 
PCCA	8653	5095	Propionic acidemia	AR	Pediatric		Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Hematologic; Neurologic	Biochemical; Cardiovascular		In acute episodes, acidosis and hypoglycemia correction, with IV carnitine are beneficial (hemodialysis may be required); Dietary (including protein restriction, to decrease propiogenic substrates) and medical (eg, l-carnitine, metronidazole, N-carbamoylglutamate) therapy may be beneficial; Liver transplant may be required in some individuals; Fasting should be avoided, and care should be taken in the setting of acute stressors; Individuals are at risk for manifestations such as cardiovascular aberrations, and surveillance may be beneficial	4815259; 10502773; 17051315; 19157943; 20301313; 22033733; 22593918 ; 23053474 
PCCB	8654	5096	Propionic acidemia	AR	Pediatric		Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Hematologic; Neurologic	Biochemical; Cardiovascular		In acute episodes, acidosis and hypoglycemia correction, with IV carnitine are beneficial (hemodialysis may be required); Dietary (including protein restriction, to decrease propiogenic substrates) and medical (eg, l-carnitine, metronidazole, N-carbamoylglutamate) therapy may be beneficial; Liver transplant may be required in some individuals; Fasting should be avoided, and care should be taken in the setting of acute stressors; Individuals are at risk for manifestations such as cardiovascular aberrations, and surveillance may be beneficial	10502773; 17051315; 19238581; 20301313; 22593918; 22033733; 23053474 
PCDH15	14674	65217	Deafness, autosomal recessive 23; Usher syndrome, type 1F; Usher syndrome, type 1D/F, digenic	AR/Digenic	Pediatric		Audiologic/Otolaryngologic; Ophthalmologic	Audiologic/Otolaryngologic	Inheritance can be digenic, involving CDH23	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	11398101; 14570705; 15537665; 17653769; 18719945; 19107147
PCDH19	14270	57526	Epileptic encephalopathy, early infantile, 9	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18469813; 19214208; 19752159; 20830798; 20713952; 21519002; 21777234; 22050978; 22267240; 22633638; 22848613; 22949144 
PCNA	8729	5111	Ataxia-telangiectasia-like disorder 2	AR	Pediatric		Dermatologic; Neurologic; Oncologic; Ophthalmologic	Oncologic		An individual has been described with evidence of predisposition to malignancy related to sun exposure, and preventive measures and surveillance may allow prevent oncologic disease and allow early diagnosis and management	24911150
PCNT	16068	5116	Microcephalic osteodysplastic primordial dwarfism, type II	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General	Individuals may have cerebral neurovascular anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7201238; 9800906; 9800908; 12400072; 12210304; 15368497; 15372530; 18157127; 18174396; 20358609; 19643772; 21567919
PCSK1	8743	5122	Proprotein convertase 1/3 deficiency	AD	N/A	N/A	Endocrine; Gastrointestinal	Gastrointestinal	Endocrinologic interventions can allow induction of secondary sex characteristic and reproduction	Presentations may be diverse, and interventions such as early parenteral nutrition may be necessary	7477119; 9207799; 14617756; 17595246
PCSK9	20001	255738	Hypercholesterolemia, familial, 3	AD	Pediatric		Cardiovascular	Cardiovascular		Interventions to maintain lipid profiles at a more desirable level can decrease morbidity/mortality, such as relates to CAD	10205269; 10764678; 12730697; 15166014; 14727156; 14727179; 15654334; 15772090; 16554528; 16909389; 18354102; 22683120 
PCYT1A	8754	5130	Spondylometaphyseal dysplasia with cone-rod dystrophy	AR	N/A	N/A	Musculoskeletal; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24387990; 24387991
PDCD10	8761	11235	Cerebral cavernous malformations 3	AD	Pediatric		Cardiovascular; Neurologic	Cardiovascular; Neurologic; Pharmacogenomic		Surveillance measures (eg, spinal cord MRI, annual brain gradient echo or susceptibility-weighted imaging) has been advocated; Agents that increase risk of hemorrhage should be avoided (eg, aspirin, NSAIDs, heparin, warfarin)	15543491; 16380626; 18060436; 19088123; 20301470; 21029238; 23485406; 23595507; 23663874
PDE11A	8773	50940	Pigmented nodular adrenocortical disease, primary, 2	AD	Pediatric		Endocrine	Endocrine		Treatment of adrenal disease (eg, potentially including surgical intervention) may be beneficial	16767104; 20351491; 21115159 
PDE4D	8783	5144	Acrodysostosis 2, with or without hormone resistance	AD	Pediatric		Cardiovascular;Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic	Cardiovascular; Endocrine		Individuals have been described with cardiovascular anomalies, including deep vein thrombosis, and awareness may allow early recognition and treatment; Individuals have been described with endocrine anomalies, including parathyroid hormone resistance and hypogonadism, and awareness may allow surveillance and early medical interventions	11200992; 22464252; 22464250; 22464252; 23033274; 24203977
PDE6A	8785	5145	Retinitis pigmentosa 43	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7493036; 18723146; 21039428
PDE6B	8786	5158	Night blindness, congenital stationary, autosomal dominant 2; Retinitis pigmentosa 40	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8394174; 8075643; 7599633; 17044014; 18854872; 20655036 
PDE6C	8787	5146	Cone dystrophy 4	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19887631; 19615668
PDE6D	8788	5147	Joubert syndrome 22	AR	N/A		Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24166846
PDE6G	8789	5148	Retinitis pigmentosa 57	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20655036
PDE6H	8790	5149	Achromatopsia 6; Retinal cone dystrophy 3A	AD/AR	N/A	N/A	Ophthalmologic	General	Inheritance is unclear, and may involve recessive model or incomplete penetrance	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15629837; 22901948 
PDE8B	8794	8622	Pigmented nodular adrenocortical disease, primary, 3	AD	Pediatric	Allelic with Striatal degeneration, autosomal dominant (AD)	Endocrine; Neurologic	Endocrine		Treatment of adrenal disease (eg, potentially including surgical intervention) may be beneficial	15210883; 18272904; 21115159; 20085714; 20373981
PDGFRA	8803	5156	Gastrointestinal stromal tumor	AD	Adult		Oncologic	Oncologic		Individuals may be at high risk for the development of gastrointestinal stromal tumor, and surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality	14699510; 17087943
PDGFRB	8804	5159	Basal ganglia calcification, idiopathic, 4; Myofibromatosis, infantile 1	AD	N/A	N/A	Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23255827; 23731537; 23731542
PDHA1	8806	5160	Pyruvate dehydrogenase E1-alpha deficiency; Leigh syndrome, X-linked	XL	Pediatric		Biochemical; Neurologic	Biochemical		Therapy may not be effective in many individuals, but dietary (ketogenic diet) and medical (eg, thiamine) therapy may be beneficial	5786203; 4343503; 824610; 413346; 40508602537010; 1293379; 1301207; 7692352; 7880337; 7808831; 8032855; 8199595; 8498846; 9727848; 10486093; 12379317; 12621116; 15138885; 18197404; 18398624; 18504677; 19517265; 19639391; 20002461; 20301764; 20462777; 21470495; 21914562; 23021068
PDHB	8808	5162	Pyruvate dehydrogensae E1-beta deficiency	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15138885; 21914562 
PDHX	21350	8050	Pyruvate dehydrogenase E3-binding protein deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		Medical and dietary treatment (eg, ketogenic diet) may be beneficial	2112155; 8229524; 8584393; 9399911; 9501264; 10590436; 11935326; 12208141; 12557299; 15303005; 16566017; 16843025; 17152059; 20002125; 21914562; 21937992; 22766002 
PDK3	8811	5165	Charcot-Marie-Tooth disease, X-linked	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23297365
PDP1	9279	54704	Pyruvate dehydrogenase phosphatase deficiency	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15855260; 19184109
PDSS1	17759	23590	Coenzyme Q10 deficiency	AR	Pediatric		Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Renal	Biochemical		There can be a wide range of manifestations, and in some individuals, treatment with Coenzyme Q10 supplementation can be beneficial	17332895; 22231380 
PDSS2	23041	57107	Coenzyme Q10 deficiency	AR	Pediatric		Biochemical; Neurologic; Renal	Biochemical		Treatment with Coenzyme Q10 supplementation may be beneficial	17186472; 22231380 
PDX1	6107	3651	Pancreatic agenesis 1; Neonatal diabetes mellitus	AR	Pediatric	Heterozygous variants are associated with Maturity-onset diabetes of the young, type 4 (AD)	Endocrine; Gastrointestinal	Endocrine; Gastrointestinal		Individuals may manifest in infancy with findings including intrauterine growth retardation, postnatal growth deficiency, and signs of diabetes mellitus (eg, hyperglycemia, glycosuria), as well as severe dehydration, and recognition can allow preventive measures related to potential sequelae, surveillance (eg, with blood glucose monitoring as well as surveillance for other common sequelae of diabetes mellitus affecting systems such as the renal and ophthalmogic systems); In the case of an acute diabetic crisis, rapid treatment (eg, with rehydration and IV insulin, transitioning to SQ insulin when stable) is indicated, though rapid-acting and (non-continuous) short-acting insulin preparations may result in severe hypoglycemia in young patients; Due to exocrine (as well as endocrine) pancreatic insufficiency, some individuals may benefit from enzymatic replacement	8506821; 9326926; 8988180; 9649577; 10545531; 10545530; 10720084; 11575290; 12970316; 19496967; 20009086; 20301620; 20546293; 20621032; 21521318; 22124438; 23320570
PDYN	8820	5173	Spinocerebellar ataxia 23	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15306549; 21035104
PDZD7	26257	79955	Usher syndrome, type IIC	Digenic	Pediatric		Audiologic/Otolaryngologic; Ophthalmologic	Audiologic/Otolaryngologic	Digenic inheritance  (with GRP98) has been described	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	20440071
PEPD	8840	5184	Prolidase deficiency	AR	Pediatric		Allergy/Immunology/Infectious; Biochemical; Craniofacial; Dermatologic; Musculoskeletal; Neurologic	Allergy/Immunology/Infectious		Individuals may have a number of manifestations, including frequent and severe respiratory and other infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	4828441; 874681; 908977; 7095220; 6727550; 1972707; 8198124; 8900231; 12384772; 16470701; 18340504; 19308961; 19937054 
PER2	8846	8864	Advanced sleep phase syndrome, familial	AD	N/A	N/A	Neurologic	General		The clinical relevance is unclear	15800623
PET100	40038	100131801	Mitochondrial complex IV deficiency	AR	N/A	N/A	Biochemical; Neurologic; Musculoskeletal; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24462369
PEX1	8850	5189	Peroxisome biogenesis factor disorder 1; Adrenoleukodystrophy, neonatal; Refsum disease, infantile; Zellweger syndrome-1  	AR	N/A	N/A	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9398848; 9398847; 9817926; 9539740; 10447258; 11389485; 12402331; 12032265; 15098231; 16086329; 16088892; 16141001; 20212125; 21844578; 22378672 
PEX10	8851	5192	Peroxisome biogenesis disorder 6B; Peroxisome biogenesis factor disorder 10; Adrenoleukodystrophy, neonatal; Zellweger syndrome; Ataxia, autosomal recessive	AR	N/A	N/A	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9700193; 9683594; 12794690; 10862081; 17041890; 19127411; 20695019 
PEX11B	8853	8799	Peroxisome biogenesis factor disorder 14B	AR	N/A	N/A	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22581968
PEX12	8854	5193	Peroxisome biogenesis factor disorder 12	AR	N/A	N/A	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9090384; 9354782; 9632816; 9792857; 14571262; 17041890; 17534573 
PEX13	8855	5194	Peroxisome biogenesis factor disorder 13; Zellweger syndrome; Adrenoleukodystrophy, neonatal 	AR	N/A	N/A	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9480815; 10441568; 10332040; 17041890; 19449432
PEX14	8856	5195	Peroxisome biogenesis factor disorder 14; Zellweger syndrome	AR	N/A	N/A	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15146459; 18285423; 21686775 
PEX16	8857	9409	Peroxisome biogenesis factor disorder 16	AR	N/A	N/A	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9837814; 11890679; 20647552
PEX19	9713	5824	Peroxisome biogenesis disorder, 19; Zellweger syndrome	AR	N/A	N/A	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9727033; 10051604; 20683989
PEX2	9717	5828	Peroxisome biogenesis disorder 5A; Peroxisome biogenesis disorder 5B	AR	N/A	N/A	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1546315; 7541833; 10528859; 14630978; 17041890; 21392394 
PEX26	22965	55670	Peroxisome biogenesis factor disorder, 26; Adrenoleukodystrophy, neonatal; Refsum disease, infantile; Zellweger syndrome	AR	N/A	N/A	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12851857; 12717447; 15542397; 15858711; 19105186 
PEX3	8858	8504	Peroxisome biogenesis factor disorder 3; Zellwegger syndrome complementation group G	AR	N/A	N/A	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10968777; 10679269; 10942428
PEX5	9719	5830	Peroxisome biogenesis disorder, 5; Zellweger syndrome; Adrenoleukodystrophy, neonatal	AR	N/A	N/A	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7719337
PEX6	8859	5190	Peroxisome biogenesis disorder, 6; Zellweger syndrome	AR	N/A	N/A	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8940266; 8670792; 10408779; 11355018; 17041890; 19877282; 21937992; 22894767 
PEX7	8860	5191	Refsum disease	AR	Pediatric	Allelic with Peroxisome biogenesis disorder (AR); Rhizomelic chondrodysplasia punctata, type 1 (AR)	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic	Biochemical		Dietary measures (eg, phytanic acid restriction, high calorie diet) can help with dermatologic and neurologic manifestations;  Surveillance and medical carefor cardiac arrhythmias and cardiomyopathy can reduce morbidity/mortality; Plasmapheresis/lipid apheresis may be used; Fasting and ibuprofen should be avoided	18140089; 13045168; 4159604; 85164; 6160883; 2452736; 7541833; 9090381; 9090382; 9090383; 12325024; 11781871; 12522768; 14974078; 17325280; 20301527; 23352163
PFKM	8877	5213	Glycogen storage disease VII	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Ophthalmologic; Renal	Cardiovascular; Musculoskeletal; Renal		There is a wide range of types and severity, but avoidance of excessive exercise may be beneficial in order to avoid renal sequale; Surveillance for cardiovascular complications (eg, cardiac hypertrophy) may allow early detection and treatment 	14339001; 4228297; 4228753; 4258222; 6444532; 6444721; 6943439; 6220601; 2945125; 2960695; 2140573; 1533013; 8444874; 8037209; 7513946; 7550225; 7479776; 8889589; 9389749; 22133655; 22364848 
PFN1	8881	5216	Amyotrophic lateral sclerosis 18	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22801503; 23141414
PGAM2	8889	5224	Glycogen storage disease X	AR	Pediatric		Biochemical; Musculoskeletal; Renal	Renal		Preventive measures to reduce the chance of severe sequelae can be beneficial, as individuals can present with exercise intolerance, and renal failure has been described	6283419; 6262916; 6308514; 8447317; 10545043; 19273759 
PGAP1	25712	80055	Mental retardation, autosomal recessive 42	AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24784135
PGAP2	17893	27315	Hyperphosphatasia with mental retardation syndrome 3	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21629298; 21643797; 23561846; 23561847
PGAP3	23719	93210	Hyperphosphatasia with mental retardation syndrome 4	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22315194; 24439110
PGK1	8896	5230	Phosphoglycerate kinase 1 deficiency	XL	Pediatric		Hematologic; Musculoskeletal; Neurologic; Renal	Hematologic; Musculoskeletal; Renal		Individuals (males by report) may have partially transfusion-dependent anemia, as well as hemolytic crises requiring measures such as exchange transfusion; Rhabdomyolysis leading to acute renal failure has also been reported, and 	5764452; 6933565; 7082849; 3605066; 2715616; 1547346; 7577653; 9512313; 16412025; 16567715; 17222195; 22705348 
PGM1	8905	5236	Congenital disorder of glycosylation, type It	AR	Pediatric		Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Renal	Biochemical; Cardiovascular; Hematologic; Pharmacogenomic; Renal		Treatment with galactose has been described as beneficial (including related to individuals with reported hypogonadotropic hypogonadism); Individuals may have exercise-induced intolerance with episodic rhabdomyolysis, and precautions may decrease associated morbidity; Individuals have been described with dilated cardiomyopathy, and surveillance may allow early medical management; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery; Hepatic-metabolized agents should be avoided; Cardiac transplant has been described	19625727; 22492991; 24499211
PGM3	8907	5238	Immunodeficiency 23	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Oncologic	Allergy/Immunology/Infectious; Oncologic		Individuals are susceptible to recurrent and severe viral, bacterial, and fungal infections (as well as sequelae such as EBV-related lymphoma), and and prophylaxis, as well as prompt and aggressive treatment of infections may be beneficial	14981714; 24589341; 24698316; 24931394
PHC1	3182	1911	Primary microcephaly 11	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23418308
PHEX	8918	5251	Hypophosphatemic rickets, X-linked dominant	XL	Pediatric		Cardiovascular; Dental; Musculoskeletal; Neurologic; Renal	Cardiovascular; Renal		Frequent oral administration of phosphate and high-dose calcitriol can be beneficial for bowing of long bones during growth and for pain; Diagnosis can help avoid therapies that may result in adverse sequelae; Due to reported cardiovascular manifestations (eg, hypertension, left ventricular hypertrophy), surveillance may allow early diagnosis and management	4305189; 4333173; 188828; 2984933; 3839245; 2571821; 1660099; 1660098; 1414477; 1464657; 7550339; 9106524; 9253316; 9768646; 10874297; 12915641; 14769584; 16055933; 18252791; 21050253; 21524226; 22319799
PHF6	18145	84295	Borjeson-Forssman-Lehmann syndrome	XL	N/A	N/A	Craniofacial; Endocrine; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13871358; 4465467; 12415272; 15241480; 14756673; 15994862; 16912705; 19264739; 22190899; 23906836
PHF8	20672	23133	Mental retardation syndrome, X-linked, Siderius type	XL	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10398231; 16199551; 17594395; 17661819; 23092983
PHGDH	8923	26227	Phosphoglycerate dehydrogenase deficiency	AR	Pediatric	Allelic with Neu-Laxova syndrome 1 (AR)	Biochemical; Craniofacial; Dermatologic; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary	Biochemical	Neu-Laxova syndrome can involve multiple congenital anomalies	Amino acid therapy (eg, with L-serine, glycine) can be beneficial, especially if early treatment is inititiated (reports include benefits to prenatal treatment)	8739971 ; 8758134; 11055895; 12118526; 15610810; 16763900; 19235232; 20196394; 21113737; 24836451
PHKA1	8925	5255	Glycogen storage disease, type Ixd	XL	Pediatric		Biochemical; Musculoskeletal; Renal	Pharmacogenomic; Musculoskeletal; Renal		Individuals should avoid circumstances such as vigorous exercise as well as certain medications (eg, succinylcholine, statins) due to risk of rhabdomyolysis	2252364; 7874115; 9731190; 12825073; 21634085 
PHKA2	8926	5256	Glycogen storage disease, type IXa1/Glycogen storage disease, type IXa2 (Phosphorylase kinase deficiency)	XL	Pediatric		Biochemical; Gastrointestinal; Musculoskeletal; Neurologic	Biochemical; Gastrointestinal		In Liver PhK deficiency, dietary management can prevent and treat hypoglycemia during acute and stable periods; Specific hepatic surveillance is indicated in childhood; Other interventions have also been reported as beneficial	5306139; 4518931; 280544; 2303074; 7711737; 7847371; 8733134; 9600238; 9835437; 9870210; 10330341; 11286390; 12809646; 12862311; 16354226; 17581768; 17689125; 19856867; 21131218; 21646031; 21634085; 21844581; 21857251; 21911307; 24055370
PHKB	8927	5257	Glycogen storage disease IXb	AR	Pediatric		Biochemical; Gastrointestinal; Musculoskeletal	Biochemical; Gastrointestinal; Musculoskeletal		Dietary measures to prevent sequelae (eg, frequent feedings high in complex carbohydrates/protein), as well as specific measures if hypoglycemia/ketosis is present (eg, Polycose, fruit juice, IV glucose) can be beneficial; Surveillance liver ultrasonography is indicated in childhood; Certain diets and medications should be avoided (eg, copious simple sugars, sulfonylureas, alcohol, succinylcholine, statins), as well as vigorous exercise	6938920; 6422139; 9215682; 17689125; 21646031; 21634085
PHKG2	8931	5261	Glycogen storage disease IXc	AR	Pediatric		Biochemical; Gastrointestinal; Musculoskeletal; Neurologic	Biochemical; Gastrointestinal		In Liver PhK deficiency, dietary management can prevent and treat hypoglycemia during acute and stable periods; Specific hepatic surveillance is indicated in childhood; Other interventions have also been reported as beneficial	6952760; 6962066; 8896567; 9245685; 9384616; 10905889; 12930917; 17689125; 21646031; 21634085; 24102521
PHOX2A	691	401	Fibrosis of extraocular muscles, congenital, 2	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11600883
PHOX2B	9143	8929	Central hypoventilation syndrome, congenital; Neuroblastoma with Hirschsprung disease; Neuroblastoma, susceptiblity to, 2	AD	Pediatric		Gastrointestinal; Neurologic; Oncologic	Neurologic; Oncologic	 Individuals are also at risk of additional autonomic nervous system anomalies including Hirschsprung disease	In Central hypoventilation syndrome, congenital, early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality; In Neuroblastoma, susceptibility to, 2 and Neuroblastoma with Hirschsprung disease, surveillance and/or awareness of cancer risk (involving the sympathetic nervous system) may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality	10390427; 12640453; 14566559; 15024693; 16873766; 16691592; 20301600 
PHYH	8940	5264	Refsum disease	AR	Pediatric		Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	Biochemical; Cardiovascular; Pharmacogenomic		Dietary measures (high calorie diet with phytanic acid restriction) may be beneficial; Surveillance can allow early diagnosis and treatment of cardiac manifestsations (eg, cardiac arrhythmias, cardiomyopathy); Plasmapheresis/lipid apheresis may be indicated in severe situations; Certain agents/circumstances (eg, fasting, ibuprofen) should be avoided  	13045168; 18140089; 4159604; 85164; 6160883; 2452736; 9326939; 9326940; 10767344; 17905308; 20301527; 20547622; 22156782 
PHYKPL	28249	85007	Phosphohydroxylysinuria 	AR	N/A	N/A	General	General	Individuals have been described with multiple phenotypes, but the overall consequences are unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2387074; 23242558
PIEZO2	26270	63895	Distal arthrogryposis type 3; Distal arthrogryposis type 5; Marden-Walker syndrome	AD	N/A	N/A	Craniofacial; Musculoskeletal; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23487782; 24726473
PIGA	8957	5277	Multiple congenital anomalies-hypotonia-seizures syndrome 2	XL	N/A	N/A	Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22305531
PIGM	18858	93183	Glycosylphosphatidylinositol deficiency	AR	Pediatric		Biochemical; Hematologic; Neurologic	Biochemical; Hematologic; Neurologic; Pharmacogenomic		Medical treatment may be beneficial (eg, prophylactic oral anticoagulants to prevent thrombosis; butyrate for seizure control);  Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery; Hepatic-metabolized agents should be avoided	16767100; 17442906; 19168132 
PIGN	8967	23556	Multiple congenital anomalies-hypotonia-seizures syndrome 1	AR	N/A	N/A	Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Genitourinary; Neurologic; Renal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21493957; 24253414
PIGO	23215	84720	Hyperphosphatasia with mental retardation syndrome 2	AR	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22683086
PIGV	26031	55650	Hyperphosphatasia with mental retardation syndrome 1	AR	N/A	N/A	Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5465362; 1724113; 16638507; 17351347; 20080219; 20802478; 20578257; 21739589; 22315194 
PIGW	23213	284098	Hyperphosphatasia with mental retardation syndrome 5	AR	N/A	N/A	Craniofacial; Gastrointestinal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24367057
PIK3CA	8975	5290	Cowden syndrome 5	AD	Adult		Dermatologic; Endocrine; Oncologic	Oncologic		Individuals have been reported with a variety of types of cancer, including breast, thyroid, renal, and endometrial cancer, and surveillance and awareness may allow early detection and management of neoplastic disease	23246288
PIK3CD	8977	5293	Immunodeficiency 14	AD	Pediatric		Allergy/Immunology/Infectious; Oncologic	Allergy/Immunology/Infectious; Oncologic		Individuals have been described as having a primary immunodeficiency, with susceptibility to respiratory and other infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals have been described as developing lymphoma, and awareness may allow early recognition and management	24136356; 24165795; 24610295
PIK3R1	8979	5295	Agammaglobulinemia 7, autosomal recessive	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may demonstrate susceptibility to severe infections (in addition to autoimmune-type sequelae in some conditions) and prophylactic measures (eg, including IVIG administration), as well as early and aggressive treatment of infections, has been reported as being beneficial	7705412; 22351933; 25133428
PIK3R2	8980	5296	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17675034; 22729224; 23745724
PIK3R5	30035	23533	Ataxia-oculomotor apraxia 3	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22065524
PIKFYVE	23785	200576	Corneal fleck dystrophy	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15902656
PINK1	14581	65018	Parkinson disease 6, autosomal recessive, early onset	AR	N/A	N/A	Neurologic	General	Heterozygotes may display more subtle signs of disease, and have been described as susceptibility alleles; Response to levodopa has been documented	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15505170; 15349870; 15087508; 15955954; 15970950; 16969854; 17030667; 16769864; 16966503; 16632486; 18685134; 18541801; 21784538; 22581678; 22956510 
PIP5K1C	8996	23396	Lethal congenital contractural syndrome 3	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17701898
PITPNM3	21043	83394	Cone-rod dystrophy 5	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8586428; 17377520; 18188949; 22405330 
PITX1	9004	5307	Clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly	AD	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18950742; 21775501; 22258522
PITX2	9005	5308	Axenfeld-Rieger syndrome, type 1; Peters anomaly; Ring dermoid of cornea; Iridogoniodysgenesis, type 2 	AD	Adult		Dental; Ophthalmologic	Ophthalmologic; Pharmacogenomic	Severe and difficult to treat glaucoma has been reported in many individuals with Peters anomaly	Individuals have a high risk of developing glaucoma, but treatment may not be effective in the majority of cases; Agents that may contribute to glaucoma should be avoided	4953922; 6029228; 6871144; 2594319; 7581385; 8944018; 9437321; 9618168; 10051017; 11004268; 11929847; 12015277; 15591271; 17197537; 22569110 
PITX3	9006	5309	Cataract, posterior polar, 4; Cataract, congenital; Cataract, posterior polar 4, syndromic; Anterior segment mesenchymal dysgenesis	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6801987; 9620774; 10361984; 15286169; 16565358; 17888164; 18989383; 21633712; 22223473 
PKD1	9008	5310	Polycystic kidney disease, adult type I	AD	Pediatric		Cardiovascular; Gastrointestinal; Renal	Cardiovascular; Gastrointestinal; Pharmacogenomic; Renal		A number of manifestations can benefit from surveillance and early treatment, including surveillance for cardiovascular findings such as intracranial aneurysms and aortic dilation can allow early detection and treatment; Treatment for hypertension is frequently required (eg, with ACE inhibitors/angiotensin II receptor blockers); A number of agents should be avoided, including nephrotoxic agents, estrogens, smoking and agents that increase renal cysts; Additional considerations related to hepatic and other cyst-related manifestations may be beneficial 	13723091; 5641158; 6102642; 6766288; 6835317; 3419455; 2198396; 1670785; 1513348; 1583643; 8004675; 7633405; 9650770; 11359016; 11134267; 11752048; 12842373; 12900587; 15458452; 15086900; 12631134; 14581387; 15034105; 14531813; 17699192; 16354965; 17699202; 16707749; 17035604; 16775462; 18299682; 17699395; 17533013; 17434405; 19443633; 19470662; 20301424; 20219616; 21551026; 21544064; 21333426 
PKD2	9009	5311	Polycystic kidney disease 2	AD	Pediatric		Cardiovascular; Gastrointestinal; Renal	Cardiovascular; Gastrointestinal; Pharmacogenomic; Renal		A number of manifestations can benefit from surveillance and early treatment, including surveillance for cardiovascular findings such as intracranial aneurysms and aortic dilation can allow early detection and treatment; Treatment for hypertension is frequently required (eg, with ACE inhibitors/angiotensin II receptor blockers); A number of agents should be avoided, including nephrotoxic agents, estrogens, smoking and agents that increase renal cysts; Additional considerations related to hepatic and other cyst-related manifestations may be beneficial 	8650545; 9402976; 9326320; 9773786; 9573526; 11156533; 11752048; 17699192; 17699202; 16707749; 17035604; 19443633; 20301424; 20219616; 21544064; 21551026 
PKHD1	9016	5314	Polycystic kidney disease, autosomal recessive	AR	Pediatric		Allergy/Immunology/Infectious; Endocrine; Gastrointestinal; Renal	Allergy/Immunology/Infectious; Gastrointestinal; Pulmonary; Pharmacogenomic; Renal		Initially, neonates may require interventions related to compromises in respiratory and renal function, including surgical interventions and dialysis as necessary (renal transplant may be indicated as well); Surveillance and interventions for complications related to systemic and portal hypertension can be beneficial;  Medical treatment (eg, with ACE inhibitors or ARBs) can be beneficial; Other interventions, such as nutritional and endocrinological (eg, GH treatment) support may be beneficial; Prophylaxis against specific infectious agents is indicated; Certain types of medications, such as sympathomimetic or nephrotoxic agents should be avoided or used judiciously if necessary	13764315; 4688793; 2702087; 7554350; 11919560; 12506140; 12728091; 15108277; 15706593; 16523049; 21896375; 20301501; 21046169; 22464505; 22882926; 23041322; 23941846; 24114580; 24162162
PKLR	9020	5313	Pyruvate kinase deficiency	AR	Pediatric	Allelic with Elevation of red blood cell ATP levels, familial (AD)	Hematologic	Hematologic		In some individuals, due to severe anemia, RBC transfusion and/or splenectomy may be beneficial	13924348; 13919474; 14014643; 14255553; 14300761; 4160306; 5940199; 7426754; 1896471; 1536957; 8285758; 7949104; 7706479; 8161798; 8807089; 8664896; 8579052; 8616073; 9090535; 9057665; 9160692; 9657767; 9886305; 10772876; 9827908; 12393511; 15491302; 15953013; 15982340; 16704447; 18420493; 18759866; 19085939; 19743919; 23082140 
PKP1	9023	5317	Ectodermal dysplasia/skin fragility syndrome	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9326952; 10951270; 1615972; 19016709; 22309335 
PKP2	9024	5318	Arrhythmogenic right ventricular dysplasia, familial 9	AD	Pediatric		Cardiovascular	Cardiovascular		Due to risk of severe sequelae including sudden cardiac death, individuals require ICD placement regardless of classic risk factors related to ICD necessity in clinically similar patients without PKP2 mutations	15489853; 16549640; 20301310 
PLA2G4A	9035	5321	Phospholipase A2, group IV A, deficiency of	AR	Pediatric		Gastrointestinal; Hematologic	Gastrointestinal; Hematologic		Surveillance for bleeding complications may be beneficial, as a described individual had chronic GI blood loss from childhood, with multiple small intestinal ulcers discovered in the context of severe bleeding and perforations during adulthood; Awareness of GI complications, including Cryptogenic multifocal ulcerating stenosing enteritis, as has been described in one pair of siblings, may allow early medical and/or surgical management	18451993; 23268370 
PLA2G5	9038	5322	Fleck retina, familial benign	AR	N/A	N/A	Ophthalmologic	General		The clinical relevance is unclear	8703867; 17502520; 22137173
PLA2G6	9039	8398	Parkinson disease 14, autosomal recessive; Neurodegeneration with brain iron accumulation 2A; Neurodegeneration with brain iron accumulation 2B	AR	N/A	N/A	Neurologic	General	In Parkinson disease 14, response to levodopa has been documented; Some individuals with Neurodegeneration with brain iron accumulation have been described as having Karak syndrome	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17033970; 16783378; 18443314; 18981035; 18570303; 20584031; 20886109; 20938027; 21520282; 21700586; 21812034; 22934738 
PLA2G7	9040	7941	Platelet-activating factor acetylhydrolase deficiency	AR	N/A	N/A	Biochemical; Pulmonary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3198761; 8675689; 10194471; 10733466
PLAGL1	9046	5325	Diabetes mellitus, transient neonatal	AD	Pediatric		Endocrine	Endocrine	The pathogenesis may involve loss of methylation	Individuals present early in life with failure to thrive, hyperglycemia, and dehydration, and prompt recognition and treatment can reduce morbidity	11448939; 20803656 
PLAU	9052	5328	Quebec platelet disorder	AD	Pediatric		Hematologic	Hematologic		Fibrinolytic inhibitors can be effective for treatment of bleeding disorder	15026313; 18988861; 20007542
PLCB1	15917	23236	Epileptic encephalopathy, early infantile, 12	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20833646; 22690784
PLCB4	9059	5332	Auriculocondylar syndrome 2 	AD	N/A	N/A	Craniofacial	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16114046; 22560091
PLCD1	9060	5333	Leukonychia totalis and/or partialis	AD/AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21665001
PLCE1	17175	51196	Nephrotic syndrome, type 3	AR	N/A	N/A	Renal	General	Most described individuals have had steroid-resistant disease	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17086182; 18065803; 20591883; 21415313; 23349334; 23595123
PLCG2	9066	5336	Familial cold autoinflammatory syndrome 3 (PLAID); Autoinflammation, antibody deficiency, and immune dysregulation syndrome (APLAID)	AD	Pediatric		Allergy/Immunology/Infectious; Dermatologic	Allergy/Immunology/Infectious		Individuals with Familial cold autoinflammatory syndrome 3 (PLAID) may be susceptible to recurrent and severe infections, and prophylaxis (eg, with IVIG) as well as early and aggressive treatment of infections may be beneficial; Individuals with APLAID may present with multi-system inflammation (eg, affecting the skin and GI system), and may demonstrate immune deficiency (eg, with frequent upper respiratory infections), and medical treatment (eg, with IL1 antagonists and high-dose corticosteroids) has been reported as beneficial	19910034; 22236196 ; 23000145
PLEC	9069	5339	Muscular dystrophy, limb-girdle, type 2Q; Epidermolysis bullosa simplex with pyloric atresia; Epidermolysis bullosa simplex with muscular dystrophy; Epidermolysis bullosa simplex, Ogna type 	AR	N/A	N/A	Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7136614; 3355199; 2662909; 8894687; 8696340; 10446808; 10570379; 11122061; 11851880; 14675180; 15681471; 15654962; 21109228; 21263134; 21674528 
PLEKHG5	29105	57449	Charcot-Marie-Tooth disease C, recessive intermediate; Spinal muscular atrophy, distal, autosomal recessive, 4	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16728649; 17564964; 23777631; 23844677
PLEKHM1	29017	9842	Osteopetrosis, autosomal recessive 6	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17404618
PLG	9071	5340	Plasminogen deficiency, type I	AR	Pediatric		Dermatologic; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic; Pulmonary	Hematologic; Ophthalmologic		Medical treatment (eg, with hyaluronidase-containing eyedrops, topical corticosteroids, heparin, FFP, immunosuppression, and lysine-conjugated plasminogen) has been described as variably beneficial	3723296; 9242524; 9834305; 10233898; 16849641; 17900274; 21174000 
PLIN1	9076	5346	Lipodystrophy, familial partial, type 4	AD	Pediatric		Cardiovascular; Endocrine; Gastrointestinal	Cardiovascular; Endocrine; Gastrointestinal		Medical treatment of factors such as diabetes, hypertension, and lipid abnormalities may be beneficial to reduce morbidity/mortality; Recognition and treatment of hypertriglyceridemia can help avoid sequelae such as acute pancreatitis	21345103; 21757733 
PLN	9080	5350	Cardiomyopathy, dilated, 1P; Cardiomyopathy, familial hypertrophic, 18	AD/AR	Pediatric		Cardiovascular	Cardiovascular	The severity may depend on inheritance (ie, heterozygosity vs. homozygosity/compound heterozygosity)	Surveillance and preventive measures, including medical management, may reduce morbidity and mortality	12639993; 12705874; 12610310; 16432188; 17655857; 18241046; 21167350
PLOD1	9081	5351	Ehlers-Danlos syndrome type VI	AR	Pediatric		Cardiovascular; Dermatologic; Musculoskeletal; Ophthalmologic; Renal	Cardiovascular; Ophthalmologic; Renal		EDS VI may be clinically recognizable, but care may be considered related to issues such as potential severe vascular rupture (beneficial preventive measures include blood pressure management); Adequate hydration to prevent nephroliathisis may be beneficial; Though not frequent, individuals may demonstrate ophthalmologic sequelae (eg, glaucoma), and appropriate surveillance and preventive measures may be beneficial	4342967; 5027136; 5016372; 4373475; 1184396; 429005; 2504907; 8449506; 7977351; 8574422; 9152832; 9220536; 9557891; 9686670; 15666309; 15979919; 16329110; 17100196; 19320026; 20301635; 22001912 
PLOD2	9082	5352	Bruck syndrome 2	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12881513; 15523624; 22689593 
PLOD3	9083	8985	Bone fragility with contractures, arterial rupture, and deafness	AR	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Musculoskeletal; Ophthalmologic	Audiologic/Otolaryngologic; Cardiovascular		The condition may be clinically recognizable in most individuals, but recognition may allow surveillance for and prompt treatment of vascular anomalies; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	18834968
PLP1	9086	5354	Spastic paraplegia-2; Pelizaeus-Merzbacher disease	XL	N/A	N/A	Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14452137; 4123133; 988510; 3476455; 2773936; 2479017; 8320699; 7530633; 7522741; 8012387; 10417279; 11093273; 11761472; 15694206; 16130097; 16778599; 16374829; 17438221; 17568416; 18190592; 19396823; 20660364; 21177054; 21679407; 22101368; 22343157; 22490426; 23133488 
PLS3	9091	5358	Osteoporosis and osteoporotic fractures	XL	N/A	N/A	Musculoskeletal	General	Variants may also act as susceptibility factors related to osteoporosis, fractures, and related phenotypes	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24088043
PMM2	9115	5373	Congenital disorder of glycosylation, type Ia	AR	Pediatric	 	Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	6543331; 3703266; 2890978; 3162953; 2466439; 1929507; 1293380; 8256592; 9140401; 10571009; 10527672; 10801058; 11916319; 11134235; 11343337; 11596651; 12905014; 17158594; 18203160; 20301507; 20301289; 21937992
PMP22	9118	5376	Roussy-Levy syndrome; Charcot-Marie-Tooth syndrome, type 1A; Charcot-Marie-Tooth syndrome with deafness (type 1E); Neuropathy, hereditary, with liability to pressurve palsies; Dejerine-Sottas disease; Neuropathy, inflammatory demyelinating 	AD/AR	N/A	N/A	Audiologic/Otolaryngologic; Neurologic	General	CMT, 1A can be due to a common 17p11.2 duplication; The mutation type (eg, deletions vs. duplications) influences the phenotype; Compound heterozygous mutations have been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13184660; 7139106; 2290479; 1349106; 1303281; 8422677; 7834893; 7903071; 8012388; 8210227; 7501152; 7666403; 8644705; 8981968; 9208274; 9179161; 9391880; 9543325; 9703447; 10489052; 10330345; 10211478; 11376203; 11835375; 12439896; 12499508; 12427913; 12084875; 12578939; 15205993; 17620487; 18698610; 19705173; 19888301; 20301566; 20301384; 22006697; 22190321; 22382358 
PMS2	9122	5395	Colorectal cancer, hereditary nonpolyposis type 4; Mismatch repair cancer syndrome 	AD/AR	Adult (Colorectal cancer, hereditary nonpolyposis type 4)/Pediatric (Mismatch repair cancer syndrome)		Dermatologic; Oncologic	Oncologic	Individuals may be at risk for a number of types of cancer	For surveillance, colonoscopy with polyp removal is indicated starting at (whichever is earlier) age 20-25 years or 10 years prior to the earliest familial diagnosis; Prophylactic Hysterectomy with bilateral oophorectomy may be considered after childbearing is completed; For individuals with colon cancer, surgical treatment with full colectomy (and ileorectal anastomosis) is recommended; Cigarette smoking should be avoided; For other tumor types (individuals may be at risk of a number of cancer types), awareness of cancer risk may allow early diagnosis and treatment, which may reduce morbidity and mortality; Individuals with Mismatch repair cancer syndrome are at risk of multiple types of malignancy, and awareness may allow early detection and management	8072530; 7661930; 4574005; 15077197; 17557300; 19851131; 20587412; 20301390; 22461402; 22577899; 22933731; 24434690
PNKP	9154	11284	Epileptic encephalopathy, early infantile, 10	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20118933
PNP	7892	4860	Purine nucleoside phosphorylase deficiency	AR	Pediatric		Allergy/Immunology/Infectious; Biochemical; Neurologic; Oncologic	Allergy/Immunology/Infectious ; Oncologic		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Surveillance for malignancy (eg, lymphoma has been described) can be beneficial; BMT/HSCT has been reported	5579411; 825775; 102751; 111549; 6774252; 3029074; 1931007; 1384322; 8774508; 8931706; 9067751; 9737781; 11498751; 11453975; 11902746; 17910661; 18208442; 19584574; 19733163; 19657670; 20544539; 22132981 
PNPLA1	21246	285848	Ichthyosis, congenital, autosomal recessive 10	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22246504
PNPLA2	30802	57104	Neutral lipid storage disease with myopathy	AR	N/A	N/A	Dermatologic; Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17187067; 22832386
PNPLA6	16268	10908	Boucher-Neuhauser syndrome	AR	Pediatric	Allelic with Spastic paraplegia 39 (AR)	Genitourinary; Neurologic; Ophthalmologic	Endocrine		For management related to hypogonadotropic hyponadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) may be beneficial; Related to  fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	18313024; 24355708
PNPO	30260	55163	Pyridoxamine 5'-phosphate oxidase deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical; Neurologic		Individuals may manifest with severe seizures starting in the immediate neonatal period (or even before birth), and medical treatment (with pyridoxal phosphate) can be effective as an antiepileptic agent	12200739; 12747882; 15772097
PNPT1	23166	87178	Deafness, autosomal recessive 70	AR	Pediatric	Allelic with Combined oxidative phosphorylation deficiency, 13 (AR)	Audiologic/Otolaryngologic; Biochemical; Neurologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	23084290; 23084291
POC1A	24488	25886	Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (SOFT syndrome)	AR	N/A	N/A	Craniofacial; Dental; Dermatologic; Endocrine; Genitourinary; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22840363; 22840364; 22440536
POC1B	30836	282809	Cone-rod dystrophy 20	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24945461; 25018096
POF1B	13711	79983	Premature ovarian failure 2B	XL	Pediatric		Endocrine; Obstetric	Obstetric		Genetic knowledge may allow fertility preservation such as by storing eggs	16773570
POFUT1	14988	23509	Dowling-Degos disease 2	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23684010
POGLUT1	22954	56983	Dowling-Degos disease 4	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21971768; 24387993
POLD1	9175	5424	Colorectal cancer, susceptibility to, 10	AD	Pediatric	Allelic with Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (AD)	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Endocrine; Musculoskeletal; Oncologic	Allergy/Immunology/Infectious; Oncologic	Individuals have been described such that mutations would warrant surveillance in the pediatric period	Described individuals manifest with colorectal adenomas, with a high risk of colorectal carcinoma, and screening (eg, with colonoscopy) may allow early detection and treatment, potentially ameliorating morbidity and mortality; Other neoplasms (eg, an increased risk of endometrial cancer has been reported) have been described in affected individuals, and knowledge of the increased risk may allow early detection and treatment	20631028; 23263490; 23770608; 24501277
POLE	9177	5426	Colorectal cancer, susceptibility to, 12; Facial dysmorphism, immunodeficiency, livedo, and short stature syndrome (FILS syndrome)	AD/AR	Pediatric		Oncologic	Oncologic	In Colorectal cancer, susceptibility to, individuals have been described such that mutations would warrant surveillance in the pediatric period	In Colorectal cancer, susceptibility to,  described individuals manifest edwith colorectal adenomas, with a high risk of colorectal carcinoma, and screening (eg, with colonoscopy) may allow early detection and treatment, potentially ameliorating morbidity and mortality; Other neoplasms have been described in affected individuals, and knowledge of the increased risk may allow early detection and treatment; In FILS syndrome, individuals may have immunodeficiency, and prophylactic measures and awareness of the risk of infections may allow early and aggressive treatment of infectious manifestations	23230001; 23263490; 24501277
POLG	9179	5428	Progressive external ophthalmoplegia, autosomal dominant; Progressive external ophthalmoplegia, autosomal recessive; Mitochondrial DNA depletion syndrome 4B; Sensory ataxia, dysarthria, and ophthalmoparesis; Mitochondrial DNA depletion syndrome 4A (Alpers type); Alpers syndrome;  POLG-related ataxia neuropathy spectrum disorders	AD/AR	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic	General	Conditions can include cardiomyopathy; Hepatotoxic medications should be avoided	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14851183; 14467368; 2725645; 13971413; 6033104; 4647849; 1252162; 2246481; 2067633; 8368248; 7897414; 9894877; 11431686; 11571332; 12210792; 12297582; 12825077; 15351195; 15534189; 15122711; 15477547; 15929042; 15689359; 16177225; 16130100; 16634032; 17502560; 6957900; 18487244; 18195149; 19307547; 19752458; 20301791; 20558295; 20837861; 20837862; 20142534; 20220442; 21357833; 21670405
POLG2	9180	11232	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4	AD	N/A	N/A	Biochemical; Gastrointestinal; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12975295; 15351195; 16685652; 20405137; 22155748 
POLH	9181	5429	Xeroderma pigmentosum, variant type	AR	Pediatric		Dermatologic; Oncologic	Dermatologic; Oncologic		Skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance for dermatologic manifestations can be beneficial	10398605; 10385124; 20301571; 23630442; 23651273; 23755135
POLR1C	20194	9533	Treacher Collins syndrome 3	AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Dental	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	21131976
POLR1D	20422	51082	Treacher Collins syndrome 2	AD/AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Dental	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	21131976; 24603435
POLR3A	30074	11128	Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism	AR	N/A	N/A	Dental; Endocrine; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12605447; 17159124; 20640464; 21855841
POLR3B	30348	55703	Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism	AR	N/A	N/A	Dental; Endocrine; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22036171; 22036172
POMC	9201	5443	Proopiomelanocortin deficiency	AR	Pediatric		Dermatologic; Endocrine	Endocrine		The condition can present with adrenal insufficiency, and medical treatment (eg, with glucocorticoid replacement therapy) can be beneficial , though may not affect certain manifestations such as obesity	9620771; 14557433; 18765507; 22570972; 23293326  
POMGNT1	19139	55624	Congenital muscular dystrophy with brain and eye anomalies, type A, 3; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 3; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11709191; 12588800; 15236414; 17030669; 17878207; 19067344; 19299310 
POMGNT2	25902	84892	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8	AR	N/A	N/A	Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22958903
POMK	26267	84197	Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A, 12; Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type C, 12; Muscle-eye brain disease; Walker-Warburg syndrome	AR	N/A	N/A	Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23519211; 24556084; 24925318
POMP	20330	51371	Keratosis linearis with ichthyosis congenita and sclerosing keratoderma	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20226437
POMT1	9202	10585	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 	AR	Pediatric		Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	Cardiovascular		Conditions may involve cardiovascular manifestations (including dilated cardiomyopathy) and surveillance (eg, with echocardiography) may allow early medical management	2494887; 11053679; 11320179; 12369018; 14678799; 15037715; 15792865; 15637732; 16717220; 16575835; 17878207; 19299310; 20065251; 22727687 
POMT2	19743	29954	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 ; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C 2	AR	Pediatric		Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	Cardiovascular		Conditions may involve cardiovascular manifestations (including dilated cardiomyopathy) and surveillance (eg, with echocardiography) may allow early medical management	15894594; 16701995; 17923109; 17878207; 19067344; 19299310; 19138766; 20301468; 20816175; 22727687  
PON1	9204	5444	Clopidogrel treatment, sensitivity to	AD/AR	Pediatric	 	General	Pharmacogenomic		Among other associations, variants may be associated with susceptibility to stent thrombosis, possibly related to clopidogrel metabolism, and may thus have pharmacogenomic importance	8896566; 11888590; 12454802; 21170047
POR	9208	5447	Antley-Bixler syndrome; Disordered steroidogenesis due to cytochrome p450 oxidoreductase deficiency	AR	Pediatric		Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic	Endocrine		Hydrocortisone replacement therapy can be effective for cortisol deficiency, including administation of stress-dose steroids; In males, testosterone therapy can help with undervirilization in puberty	2932643; 0633130; 12116245; 11742006; 12917333; 15220035; 14758361; 14513299; 15793702;  16906539; 18559916; 19837910; 19884324; 20124576; 20410220; 20818252; 20844025; 21070833; 22162478 
PORCN	17652	64840	Focal dermal hypoplasia	XL	N/A	N/A	Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13948891; 1190805; 843447; 17546031; 17546030; 18325042; 19309688; 19863546; 19586929; 20420028; 21332693; 21472892; 21484999; 21732017; 22414489; 22250236; 22735390; 23131169; 23399492
POT1	17284	25913	Melanoma, cutaneous malignant, susceptibility to 10	AD	Pediatric		Oncologic	Oncologic	Susceptibility to cancer types other than melanoma has been suggested in the reported families	Awareness of risk of melanoma (as well as other malignancies) may allow surveillance and early disease detection and management	24686846; 24686849
POU1F1	9210	5449	Pituitary hormone deficiency, combined 1	AR	Pediatric		Cardiovascular; Endocrine	Cardiovascular; Endocrine	A minority of individuals have been described with cardiac anomalies	Individuals may manifest with central deficiency of multiple hormones, which can result in severe sequelae if untreated, and replacement therapy can be effective	2634610; 1302000; 15928241; 16060904; 18059085; 19498317; 21316014; 21521297; 21722153; 22010633 
POU3F4	9217	5456	Deafness, X-linked 2	XL	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; It has been suggested that  that stapes surgery should not be performed due to a high likelihood of complications (the use of cochlear implants has been reported as beneficial)	5173351; 6662621; 1922747; 7839145; 7581392; 19438930; 19671658; 19930154; 20412083; 21193157; 21250553; 21555964; 23076972;  23606368
POU4F3	9220	5459	Deafness, autosomal dominant 15	AD	N/A	N/A	Audiologic/Otolaryngologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9506947; 18228599; 18347256; 19372648; 19462854; 20434433; 22938506
POU6F2	21694	11281	Wilms tumor 5	AD	Pediatric		Oncologic	Oncologic	Germline mutations can predispose to disease due to loss of heterozygosity	Individuals may be at high risk for Wilms tumor, and surveillance may allow early diagnosis and treatment	11284034
PPARG	9236	5468	Lipodystrophy, familial, partial, type 3; Insulin resistance, severe, digenic	AD/Digenic (Severe digenic insulin resistance can be due to digenic mutations in PPP1R3A and PPARG)	N/A	N/A	Endocrine	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9425261; 9753710; 10622252; 10973253; 11788685; 12453919; 12118251; 15356014; 21079616; 21479595; 21865368; 22748602; 22803842 
PPIB	9255	5479	Osteogenesis imperfecta, type IX	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19781681; 20089953; 22718341;  23613367
PPM1K	25415	152926	Maple syrup urine disease, mild variant	AR	Pediatric		Biochemical	Biochemical		The condition can result in neurologic sequelae, and medical/dietary treatment (with low protein diet without branched-chain amino acids) can allow normal cognitive development	23086801
PPOX	9280	5498	Porphyria variegata	AD/AR	Pediatric		Biochemical; Dermatologic; Musculoskeletal; Neurologic; Renal	Dermatologic; Pharmacogenomic	Homozygosity/compound heterozygosity results in a distinct and much more severe phenotype	Acute attacks may be precipitated by porphyrinogenic agents, which, along with other exacerbating factors, should be avoided; Skin protection is warranted	6143163; 4059081; 3723537; 3319294; 2222353; 2020301; 8852667; 8673113; 8817334; 9738863; 9811936; 10401000; 11286631; 12357337; 19460837; 19656457; 19845869; 21734717; 21910705 
PPP1R3A	9291	5506	Insulin resistance, severe, digenic	Digenic	N/A	N/A	Endocrine	General	Severe digenic insulin resistance has been reported as resulting from digenic mutations in PPP1R3A and PPARG	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12118251
PPP2R2B	9305	5521	Spinocerebellar ataxia 12	AD	N/A	N/A	Neurologic	General	The condition involves expansion of triplet repeats	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10581021; 11719278;  14526180; 16138911; 20301381; 20629122
PPT1	9325	5538	Ceroid lipofuscinosis, neuronal, 1	AR	N/A	N/A	Biochemical; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5706364; 4121459; 4698309; 6890163; 7637805; 9664077; 9425237; 9535296; 11506414; 15965709; 17261688; 21235444; 21990111 
PQBP1	9330	10084	Renpenning syndrome	XL	N/A	N/A	Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13981686; 3177467; 7943045; 9599645; 11950858; 14634649; 15024694; 15811016; 15782410; 16493439; 16740914; 17033686; 20886605; 20950397; 21204222; 21267006; 21315190; 22710169
PRCD	32528	768206	Retinitis pigmentosa 36	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16938425
PRDM16	14000	63976	Cardiomyopathy, dilated, ILL; Left ventricular noncompaction 8	AD	Pediatric		Cardiovascular	Cardiovascular		Individuals have been described as manifesting with findings such as arrhythmias, cardiac valvular abnormalities, and dilated cardiomyopathy, and surveillance (eg, with echocardiogram and electrocardiogram) may allow early medical and/or surgical interventions (eg, intracardiac defibrillator) may be beneficial in terms of reducing disease-associated morbidity and mortality	18506004; 21551322; 23768516
PRDM5	9349	11107	Brittle cornea syndrome 2	AR	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Ophthalmologic	Ophthalmologic	Manifestations can occur in heterozygote	Individuals are prone to ophthalmologic injury (such as corneal rupture) with minimal trauma, and protective measures may be beneficial	21664999
PRF1	9360	5551	Hemophagocytic lymphohistiocytosis, familial, 2; Lymphoma, non-Hodgkin; Aplastic anemia, adult-onset 	AR	Pediatric		Allergy/Immunology/Infectious; Hematologic; Oncologic	Allergy/Immunology/Infectious; Hematologic; Oncologic	Individuals with Aplastic anemia, adult-onset may have manifestations after the pediatric period	In Lymphoma, non-Hodgkin; Aplastic anemia, adult-onset, surveillance and early treatment of hematologic (eg, anemia, bone marrow failure) and malignant complications may reduce morbidity; In Hemophagocytic lymphohistiocytosis, familial, 2 (as well as Immune-mediated neurodegeneration, infection triggered, at least theoretically), antibiotics or antiviral agents can be beneficial to treat/prevent infections that can trigger an exaggerated inflammatory response; Chemo/immunotherapy can achieve clinical stability prior to allogeneic HSCT, which can be effective	10583959; 12229880; 12358924; 14757862; 15659737; 17311987; 15728124; 17873118; 21936944; 21959744; 22029169; 22186995; 22359105; 23443029 
PRG4	9364	10216	Camptodactyly-arthropathy-coxa vara-pericarditis syndrome	AR	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular		The disorder may be recognizable by noncardiac manifestations, but individuals frequently develop pericarditis refractory to other treatments and requiring pericardiectomy, and awareness may allow early detection and efficient targeted medical management	940709; 656159; 6866038; 6870971; 4083939; 3964320; 3964321; 8835575; 9550484; 10545950; 11102929; 16429407; 21565623 
PRICKLE1	17019	144165	Epilepsy, progressive myoclonic, 1B	AD/AR	N/A	N/A	Neurologic	General	As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15634728; 15642921; 16376507; 18976727; 21276947
PRICKLE2	20340	166336	Epilepsy, progessive myoclonic 5	AD	N/A	N/A	Neurologic	General	As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	632821; 21276947
PRIMPOL	26575	201973	Myopia 22, autosomal dominant	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23579484
PRKACA	9380	5566	Primary pigmented nodular adrenocortical disease 4	AD	Pediatric		Endocrine	Endocrine	Reported germline mutations have included germline copy number variants including the PRKACA gene	Awareness may allow early management of adrenal disease (eg, potentially including surgical intervention), which may be beneficial	24571724; 24700472; 24747643
PRKAG2	9386	51422	Cardiomyopathy, familial hypertrophic 6; Wolff-Parkinson-White syndrome	AD	Pediatric	Allelic with Glycogen storage disease of heart, lethal congenital (AD)	Cardiovascular; Craniofacial; Musculoskeletal; Renal	Cardiovascular		Surveillance measures (eg, including echocardiography and electrocardiography) and medical and preventive management related to cardiac hypertrophy, as well as arrhythmia, may ameliorate/prevent severe sequelae	13619017; 15371577; 10820940; 11371514; 11586962; 11827995; 15673802; 15877279; 16716659; 16487706; 18403758; 19787389
PRKAG3	9387	53632	Increased glyogen content in skeletal muscle	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17878938
PRKAR1A	9388	5573	Pigmented nodular adrenocortical disease, primary, 1; Carney complex; Myxoma, intracardiac; Acrodysostosis 1, with/without hormone resistance 	AD	Pediatric		Cardiovascular; Dermatologic; Endocrine; Musculoskeletal; Neurologic; Oncologic	Endocrine; Oncologic		Surveillance for neoplasms (eg, cardiac myxomas), as well as multiple endocrine-related manifestations can allow early detection and treatment, which can involve surgical excision of the neoplasm; Additional surveillance for endocrine abnormalities can allow early interventions	1263542; 579530; 6329005; 4010501; 3465316; 3365080; 2605794; 2586567; 1571257; 9415461; 9215269; 9805140; 10523219; 10974026; 10973256; 11549623; 12213893; 20507346; 21651393; 22464252; 22464250; 20301463 
PRKCD	9399	5580	Autoimmune lymphoproliferative syndrome type III	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; medical management (eg, with immunosuppressive agents) of autoimmune manifestations has been described as beneficial	23319571; 23430113; 23666743
PRKCG	9402	5582	Spinocerebellar ataxia 14	AD/AR	N/A	N/A	Neurologic	General	Homozygosity has been described in severe cases	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10939565; 12164726; 12644968; 14694043; 14676051; 16193476; 15841389; 19561170; 21434874; 21827914; 21937992; 22675081; 23604456
PRKCSH	9411	5589	Polycystic liver disease	AD	N/A	N/A	Gastrointestinal	General	Though some individuals may require treatment, it is unclear if early (genetic) diagnosis would be beneficial; Liver transplantion has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11047756; 12577059; 12529853; 16835903; 20095989; 22415584 
PRKDC	9413	5591	Immunodeficiency 26 with or without neurologic abnormalities	AR	Pediatric		Allergy/Immunology/Infectious; Craniofacial; Neurologic	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported	19075392; 23722905
PRKG1	9414	5592	Aortic aneurysm, familial thoracic 8	AD	Pediatric		Cardiovascular	Cardiovascular		Individuals have been described as suffering from sudden death secondary to aortic dissection/rupture, and surveillance and preventive measures, as well as early treatment of disease-related manifestations (including aortic aneurysms as well as other vascular anomalies), may help ameloriate morbidity and mortality	16646045; 23910461
PRKRA	9438	8575	Dystonia 16	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18243799; 18420150; 20408955;  22415584; 22842711
PRLR	9446	5618	Hyperprolactinemia; Multiple fibroadenomas of the breast	AD	Pediatric	Multiple fibroadenomas of the breast (AD)	Endocrine; Oncologic	Endocrine	Knowledge of variants may be additionally helpful in consideration of women with breast masses	Women may require dopamine agonists after breastfeeding in order to treat galatorrhea	18779591; 24195502
PRNP	9449	5621	Spongiform encephalopathy with neuropsychiatric features; Huntington disease-like 1; Gerstmann-Straussler disease; Creutzfeldt-Jakob disease; Insomnia, fatal familial; Dementia, Lewy body	AD/AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2573006; 2572450; 2564168; 2563037; 2190844; 1975028; 2159587; 1683708; 1677164; 1363809; 1439789; 1363810; 12451207; 1346338; 8595485; 9266722; 9384372; 9789072;  9792871; 10581230; 10371520; 9932941; 11593450; 11709001; 15623717; 16769939; 16831973; 17353478; 18360821; 19081515; 22097954; 22210626; 22488860; 22558438; 22561193; 22612156; 22675855; 22763467 
PROC	9451	5624	Thrombophilia, hereditary, due to protein C deficiency	AD/AR	Pediatric		Hematologic	Hematologic	The risks of hematologic complications may be affected by variants in other genes (eg, FVL)	Individuals can demonstrate manifestations such as severe thrombophilia and high risk for a variety of cardiovascular complications, and prophylactic measures and rapid treatment of sequelae may reduce morbidity and mortality; Liver and renal transplantation have been described	6895379; 6139528; 6148564; 6547008; 6437521; 3840918; 2958610; 2437584; 3337902; 2521802; 2547423; 1944440; 8093743; 8322701; 8446940; 8049422; 7795227; 7562967; 8750805; 10942114; 11148525; 19373522; 20187890; 20727573; 22168450; 22531345 
PRODH	9453	5625	Hyperprolinemia, type I	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13910064; 14497974; 4299764; 11510941; 12217952; 12525555; 17412540; 18197084; 18806117; 20524212; 23462603
PROK2	18455	60675	Kallmann syndrome 4; Hypogonadism, hypogonadotropic	AD/AR	Pediatric		Craniofacial; Endocrine; Neurologic	Endocrine		In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	17054399; 17959774; 18285834; 20301509
PROKR2	15836	128674	Hypogonadotropic hypogonadism 3 with or without anosmia	AD/AR	Pediatric		Craniofacial; Endocrine; Neurologic	Endocrine	Digenic inheritance (with KAL1) has been reported	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	17054399; 20301509 
PROM1	9454	8842	Cone-rod dystrophy 12; Macular dystrophy, retinal, 2; Stargardt disease 4; Retinitis pigmentosa 41	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10205271; 10587575; 12657606; 17605048; 18654668; 20393116;  20859302
PROP1	9455	5626	Pituitary hormone deficiency, combined, 2	AR	Pediatric		Endocrine	Endocrine		Hormone replacement therapy can be effective to treat multiple endocrinological deficiencies (eg, GH and thyroid hormone deficiency); Individuals may develop ACTH deficiency, and may require treatment including "stress dose steroids"; Medical interventions may be necessary to induce puberty	6046325; 745452; 9661653; 9768691; 9462743; 10084575; 920061; 11134108; 10634415; 11549674; 11549703; 15472175; 15531542; 20301521; 20381582; 20395664; 22024773; 22111336; 22286799 
PROS1	9456	5627	Thrombophilia, hereditary, due to protein S deficiency	AD/AR	Pediatric		Hematologic	Hematologic		Individuals may be at higher risk for thrombophilia, and may demonstrate thrombosis and secondary hemorrhage usually beginning in early infancy (in recessive forms); Prompt recognition may allow preventive measures and early treament, which may reduce morbidity and mortality	6239102; 6238642; 2952034; 2935209; 2231208; 2141197; 7899424; 7545463; 10442899; 10063989; 19168201; 19466456; 19826897; 20398916; 20484936; 20484936; 21172841; 21799399; 22166512 
PROZ	9460	8858	Protein Z deficiency	AD	N/A	N/A	General	General		There is weak or mixed evidence that protein Z deficiency has an adverse health effect	7495103; 10829076; 11289354; 11895801; 15638861; 14671240; 15626740; 16938126; 20076855
PRPF3	17348	9129	Retinitis pigmentosa 18	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11773002
PRPF31	15446	26121	Retinitis pigmentosa 11	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5764686; 9345108; 11545739; 12923864; 17325180; 19506198; 19618371; 20939871; 23041261 
PRPF4	17349	9128	Retinitis pigmentosa 70	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24419317
PRPF6	15860	24148	Retinitis pigmentosa 60	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21549338
PRPF8	17340	10594	Retinitis pigmentosa 13	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11468273; 20232351; 22039234
PRPH2	9942	5961	Choriodal dystrophy, central areolar 2; Retinitis punctata albescens; Macular dystrophy, vitelliform 3; Macula dystrophy, patterned 1; Retinitis pigmentosa 7	AD/Digenic	N/A	N/A	Ophthalmologic	General		Digenic inheritance (with ROM1) has been reported; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13410569; 900215; 7115165; 6984500; 3718916; 1749427; 1684223; 8485575; 8251014; 8485574; 8485572; 8485576; 7519821; 8202715; 8302543; 7493155; 8689482; 8644804; 9010868; 9443872; 10532447; 14557183; 19262438; 19243827; 20213611; 22842402; 22863181; 23847139
PRPS1	9462	5631	Arts syndrome; Deafness, X-linked 1; Phosphoribosylpyrophosphate synthetase I superactivity 	XL	Pediatric	Allelic with Charcot-Marie-Tooth disease, X-linked recessive, 5 (XL); Phosphoribosylpyrophosphate synthetase I superactivity (XL); Nonsyndromic sensorineural deafness, 2, X-linked (XL)	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Hematologic; Neurologic; Renal	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Renal		In Arts syndrome, treatment with S-adenosylmethionine may be beneficial, and due to infectious risk, prophylaxis and early and aggressive treatment of infections may decrease related morbidity and mortality; Several PRPS1-related conditions can include deafness, which can be congenital/prelingual, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Phosphoribosylpyrophosphate synthetase I superactivity, medical treatment of uric acid overproduction can be beneficial	6069085; 5782823; 171280;  6243137; 3017368; 8498830; 8253776; 7593598; 8882866; 896876310503584; 15240907; 5955956; 17701896; 17701900; 20380929; 20021999; 20301738; 22246954
PRRT2	30500	112476	Episodic kinesigenic dyskinesia 1; Seizures, benign familial infantile, 2; Convulsions, familial infantile, with paroxysmal choreoathetosis 	AD	N/A	N/A	Neurologic	General	In Episodic kinesigenic dyskinesia, treatment with antiepileptics can be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22101681; 22120146; 22243967; 22543779; 22832103; 22870186  
PRRX1	9142	5396	Agnathia-otocephaly complex	AD/AR	N/A	N/A	Audiologic/Otolaryngologic; Craniofacial	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12244557; 21294718; 22211708; 23444262
PRSS1	9475	5644	Pancreatitis, hereditary	AD	Pediatric		Gastrointestinal; Oncologic	Gastrointestinal; Oncologic		To decrease attacks, dietary measures (eg, low-fat diet), hydration, and antioxidants, with avoidance of precipitants, such as alcohol and tobacco can beneficial; Medical management (including with pancreatic enzyme replacement) may be benefiical; Individuals may be at increased risk for manifestations such as pancreatic cancer, and awareness may allow prompt detection and treatment	6023921; 8841182; 9322498; 9557894; 10204851; 22088471; 22094894; 22379635; 23503650; 23864476; 24236450; 24242859
PRSS12	9477	8492	Mental retardation, autosomal recessive 1	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12459588; 12925575
PRSS56	39433	646960	Microphthalmia, isolated 6	AR	Adult		Ophthalmologic	Ophthalmologic; Pharmacogenomic		Some individuals with angle-closure glaucoma have been described, and awareness of disease risk and surveillance may allow early treatment; Agents that may contribute to glaucoma should be avoided	15823920; 19526372; 21397065; 21532570; 21850159 
PRX	13797	57716	Dejerine-Sottas disease; Charcot-Marie-Tooth disease, type 4F 	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10848494; 11523566; 11157804; 12112076; 16534116; 21079185; 22847150
PSAP	9498	5660	Krabbe disease, atypical; Combined saposin deficiency; Gaucher disease, atypical, due to saposin C deficiency; Metachromatic leukodystrophy due to saposin-b deficiency	AR	N/A	N/A	Biochemical; Gastrointestinal; Musculoskeletal; Neurologic	General	BMT has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	41211; 6126151; 2060627; 3024666; 2615292; 2514102; 2764035; 1371116; 8460394; 8554069; 9672525; 9930900; 10682309; 11309366; 15856305; 15773042; 17919309; 19267410; 19955343; 20484222; 22652185 
PSAT1	19129	29968	Phosphoserine aminotransferase deficiency	AR	Pediatric	Allelic with Neu-Laxova syndrome 2 (AR)	Biochemical; Craniofacial; Musculoskeletal; Neurologic	Biochemical	Neu-Laxova syndrome can involve multiple congenital anomalies	Medical treatment (eg, with serine and glycine) can lead to improved outcomes, and early initiation of treatment may be beneficial	17436247; 25152457
PSEN1	9508	5663	Cardiomyopathy, dilated 1U	AD	Pediatric	Allelic with Acne inversa, familial, 3 (AD); Dementia, frontotemporal (AD/AR); Pick disease (AD); Alzheimer disease, familial (AD)	Cardiovascular; Dermatologic; Neurologic 	Cardiovascular	The reported onset of heart failure has been in the adult period (including in young adults), but surveillance and early treatment may be indicated prior to adulthood	Surveillance (eg, with echocardiography), preventive measures and medical management may be helpful to  decrease morbidity	7550356; 7596406; 7585193; 9052708; 9384602; 9521418; 9544835; 11094121; 11389157; 11524469; 12891668; 12668610; 15122701; 16216949; 16033913; 17186461; 20194882; 20929727; 21495993; 21656036 
PSEN2	9509	5664	Cardiomyopathy, dilated, 1V; Peripartum/pregnancy-associated cardiomyopathy 	AD	Pediatric	Allelic with Alzheimer disease, 4 (AD)	Cardiovascular; Neurologic; Obstetric	Cardiovascular; Obstetric		Preventive measures and medical management may be helpful to help decrease morbidity; Precautions/surveillance may be beneficial prior to/during pregnancy	7638622; 7651536; 9521418; 10822446; 11723295; 14681895; 12925374; 14623725; 17186461; 18427071; 20458009; 20457965
PSENEN	30100	55851	Acne inversa, familial, 2	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20929727
PSMB8	9545	5696	Nakajo-Nishimura syndrome; Autoinflammation, lipodystrophy, and dermatosis syndrome; Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome; Joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndrome	AR	N/A	N/A	Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic	Cardiovascular		Individuals have been described with multiple manifestations, including lethal arrhythmias, and surveillance may allow early detection and management of cardiac sequelae	6499339; 4026345; 3618123; 8495043; 21129723; 20534754; 20159315; 21852578,; 21881205; 21953331; 22441638 
PSMC3IP	17928	29893	Ovarian dysgenesis 3	AR	Pediatric		Endocrine; Genitourinary	General	To induce/maintain secondary sex characteristics, and to allow reproduction, specific interventions (eg, medical hormonal treatment) may be necessary	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21963259
PSPH	9577	5723	Phosphoserine phosphatase deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		Medical treatment (eg, with L-serine, glycine) has been reported as beneficial in terms of both biochemical parameters and clinical manifestations (head growth)	9222972; 14673469; 16763900; 19963421 
PSTPIP1	9580	9051	Pyogenic sterile arthritis, pyoderma gangrenosum, and acne	AD	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Endocrine; Musculoskeletal	Allergy/Immunology/Infectious; Pharmacogenomic		Medical treatment (eg, anakinra) can be effective to treat autoimmune manifestations; Cytopenia related to sulfonamide use has been reported	9212761; 11971877; 19673875; 21790734 
PTCH1	9585	5727	Basal cell nevus syndrome	AD	Pediatric	Variants may also be associated with Holoprosencephaly (AD), though evidence for pathogenicity is mixed (individuals with holoprosencephaly can manifest with endocrine anomalies such as diabetes insipidus, but the efficacy of early diagnosis is unclear)	Craniofacial; Dermatologic; Endocrine; Musculoskeletal; Neurologic; Oncologic	Oncologic		Individuals are at risk for a number of types of malignancies, including basal cell carcinomas and medulloblastoma , as well as (rare) malignant rare keratocyst transformation, and awareness and surveillance may allow early diagnosis and treatment (including with molecular therapies that target the Hedgehog signaling pathway), potentially reducing morbidity and mortality; Avoidance of agents such as radiation therapy is indicated	13851319; 8326488; 9096761; 9096762; 8981943; 11382639; 11941477; 16906569; 19439922; 19557015; 21368767; 22007994; 22565648; 22670903; 22670904; 22844361; 23677114
PTCH2	9586	8643	Basal cell nevus syndrome	AD	Pediatric		Dermatologic; Musculoskeletal; Oncologic	Oncologic		Individuals are at risk for a number of types of malignancies, including basal cell carcinomas and medulloblastoma , as well as (rare) malignant rare keratocysttransformation, and awareness and surveillance may allow early diagnosis and treatment (including with molecular therapies that target the Hedgehog signaling pathway), potentially reducing morbidity and mortality; Avoidance of agents such as radiation therapy is indicated	18285427;  22670903; 22670904; 23479190
PTDSS1	9587	9791	Lenz-Majewski hyperostotic dwarfism	AD	N/A	N/A	Craniofacial; Dental; Genitourinary; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24241535
PTEN	9588	5728	PTEN hamartoma tumor syndrome; Cowden syndrome; Bannayan-Riley-Ruvalcaba syndrome; Lhermitte-Duclos syndrome; Glioma susceptibility 2; Meningioma, familial; Endometrial cancer	AD	Pediatric	Allelic with Macrocephaly/autism syndrome (AD) (without reported associated malignancies); Reported as allelic with VACTERL association with hydrocephalus (AD)	Craniofacial; Dermatologic; Neurologic; Oncologic	Oncologic	Evidence for association with some cancerous processes is unclear,and the division into many separate disorders is likely specious	Surveillance is indicated to screen for the presence of neoplasms (including regular thyroid ultrasound, dermatologic examinations, breast screening including mammogram and/or MRI, transvaginal ultrasound and/or endometrial biopsy, colonoscopy, renal imaging, and other screening as specifically indicated by family or personal medical history), which may allow early diagnosis and treatment, which may be beneficial related to morbidity and mortality	5345120; 5091590; 957004; 7449178; 7079022; 6881215; 6507473; 3707175; 3698331; 3340479; 1336932; 1350505; 8207516; 9140396; 9286463; 9399897; 9241266; 9259288; 9545417; 9662392; 9832032; 9832031; 9425889; 9445133; 9856571; 10353779; 10400993; 10234502; 11238682; 11748304; 12085208; 11875759; 12938083; 14518069; 12833416; 14566704; 15805158; 16704655; 16752378; 17286265; 17526800; 17526801; 17847000; 18781191; 21659347; 21633361; 20301661; 21956414; 22595938; 22970944; 23335809; 23344409
PTF1A	23734	256297	Pancreatic and cerebellar agenesis; Pancreatic agenesis 2	AR	Pediatric		Craniofacial; Gastrointestinal; Neurologic; Ophthalmologic	Endocrine	The condition can include multiple congenital anomalies	As the conditions can include pancreatic insufficiency, awareness can allow measures to manage neonatal diabetes as well as pancreatic exocrine insufficiency	10507728; 15543146; 19650412; 21749365; 24212882
PTH	9606	5741	Hypoparathyroidism, familial isolated	AR	Pediatric		Endocrine	Endocrine		Early recognition of electrolyte abnormalitities (eg, hypocalcemia) can allow prompt treatment in order to avoid severe sequelae	3005800; 2212001; 1302009; 10523031
PTH1R	9608	5745	Eiken syndrome; Chondrodysplasia, Blomstrand type; Metaphyseal chondrodysplasia, Murk Jansen type; Failure of tooth eruption, primary 	AD/AR	N/A	N/A	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3975110; 6734674; 8276022; 7701349; 9268097; 9178745; 9649554; 9745456; 10664159; 12357475; 15525660; 17164305; 19061984; 20135246 
PTHLH	9607	5744	Brachydactyly, type E2	AD	N/A	N/A	Dental; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20170896
PTPN11	9644	5781	Noonan syndrome; LEOPARD syndrome 1	AD	Pediatric	Allelic with Metachondromatosis (AD)	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Cardiovascular; Hematologic; Oncologic; Renal		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Surveillance and treatment related to  manifestations such as cardiac anomalies (which include pulmonic stenosis, hypertrophic cardiomyopathy, and arrhythmias) can be beneficial; Can include bleeding diathesis,  and recognition and preventive measures (eg, in surgical situations) can be beneficial; Individuals appear to be at increased risk for malignancy, and although specific surveillance may not be warranted, awareness may allow prompt detection and treatment; Awareness of increased risk of renal anomalies and hydronephrosis can allow prophylaxis and early and aggressive management of related manifestations (eg, infections)	19994192; 5921856; 5638719; 5771505; 4672553; 4547387; 7193405; 6602353; 6539946; 345952; 9222968; 3232698; 11316696; 11344190; 11704759; 12058348; 11992261; 12634870; 12529711; 12717436; 15384080; 15240615; 15985475; 15956085; 15723289; 15690106; 16523510; 16263833; 16358218; 17497712; 18203203; 18678287; 18241070; 19273734; 19054014; 20602484; 20954246; 20979190; 20876176; 20577567; 20301303; 21533187; 20954246; 21407260; 21534355; 22315187; 23799168; 23813970; 23885229; 23918208; 24034393; 24444506
PTPN14	9647	5784	Choanal atresia and lymphedema	AR	N/A	N/A	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7158640; 1872518; 20826270 
PTPRC	9666	5788	Severe combined immunodeficiency, autosomal recessive, T-cell negative, B-cell positive, NK cell positive	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial; BMT has been described	9068311; 11145714; 22689986 
PTPRF	9670	5792	Breasts and/or nipples, aplasia or hypoplasia of, 2	AR	N/A	N/A	Dermatologic; Endocrine	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24781087
PTPRO	9678	5800	Nephrotic syndrome, type 6	AR	N/A	N/A	Renal	General	Renal transplant has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21722858
PTPRQ	9679	374462	Deafness, autosomal recessive 84	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	20346435; 19888295
PTRF	9688	284119	Lipodystrophy, congenital generalized, type 4	AR	N/A	N/A	Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal	Cardiovascular		Among other manifestations, individuals may demonstrate cardiac arrhythmias, and appropriate surveillance and management may be beneficial	12116229; 18698612; 19726876; 20300641; 20684003
PTS	9689	5805	Hyperphenylalaninemia, BH4-deficient, A	AR	Pediatric		Biochemical; Neurologic	Biochemical		Dietary measures and/or medical treatment (eg, L-dopa, tetrahydrobiopterin) can be beneficial	7094929; 6142058; 3297709; 3308682; 8178819; 9222757; 9222755; 2027491; 11438997; 11916314; 1388593; 16364672; 20059486 
PUS1	15508	80324	Mitochondrial myopathy and sideroblastic anemia 1	AR	Pediatric		Endocrine; Hematologic; Musculoskeletal; Neurologic	Endocrine; Hematologic		Severe, non-B6 responsive anemia has reportedly required transfusions; Additionally, individuals have required GH treatment	7726239; 14981724; 15108122; 15103716; 17056637; 19731322 
PVRL1	9706	5818	Cleft lip/palate-ectodermal dysplasia syndrome	AD/AR	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10932188; 11559849
PVRL4	19688	81607	Ectodermal dysplasia-syndactyly syndrome	AR	N/A	N/A	Dental; Dermatologic; Musculoskeletal	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1646587; 20691405; 21346770
PXDN	14966	7837	Corneal opacification with other ocular anomalies	AR	Pediatric		Ophthalmologic	Ophthalmologic		Some individual are at risk of glaucoma, and surveillance and early treatment may be beneficial; Agents that may contribute to glaucoma should be avoided	21907015; 24939590
PYCR1	9721	5831	Cutis laxa, autosomal recessive, type IIB; Cutis laxa, autosomal recessive type IIIB	AR	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4076251; 11424136; 16045708; 18304158; 18348262; 19576563; 19401719; 19648921; 21204221; 21567914; 21834030; 22052856
PYGL	9725	5836	Glycogen storage disease VI	AR	Pediatric		Biochemical	Biochemical		While therapy is frequently not necessary in many individuals, measures to maintain normoglycemia (eg, frequent feeding, uncooked cornstarch) may be beneficial	13646331; 5904467; 9529348; 9536091; 17705025; 20301788; 21646031 
PYGM	9726	5837	Glycogen storage disease V	AR	Pediatric		Biochemical; Musculoskeletal; Renal	Biochemical; Musculoskeletal; Pharmacogenomic; Renal		Avoidance of excessive exercise may be beneficial to avoid rhabdomyolysis and potential renal failure; Sucrose ingestion may be beneficial (eg, prior to exercise); Certain precautions should be taken with general anesthesia	16590445; 14442994; 4502558; 1067063; 101896; 6929403; 3808314; 3466902; 3207360; 2768781; 2391551; 8408630; 8316268; 11168025; 14695410; 16924035; 17705025; 17915571; 18667317; 19251976; 19433441; 20301518; 20957198; 21802952; 21880526; 22608882; 22818872; 22899091
QARS	9751	5859	Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy	AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24656866
QDPR	9752	5860	Hyperphenylalaninemia, BH4-deficient, C	AR	Pediatric		Biochemical; Neurologic	Biochemical		Dietary measures and/or medical treatment (eg, L-dopa, tetrahydrobiopterin) can be beneficial	53532; 49470; 317358; 2785251; 2116088; 7627180; 10029353; 11153907; 11746132; 16917893 
RAB18	14244	22931	Warburg micro syndrome 3	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21473985
RAB23	14263	51715	Carpenter syndrome	AR	N/A	N/A	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dental; Endocrine; Genitourinary; Musculoskeletal; Neurologic	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19974019; 5935752; 3322002; 17503333; 20358613; 21082653; 21412941 
RAB27A	9766	5873	Griscelli syndrome, type 2; Elejalde syndrome	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Hematologic; Neurologic; Oncologic	Allergy/Immunology/Infectious; Oncologic		Antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial; Surveillance for complications such as hemophagocytic lymphohistiocytosis to allow early medical treatment (with chemo-immunotherapy) may be beneficial in order to allow prompt medical treatment; HSCT has been described	707528; 7996360; 10835631; 12058346; 15452859; 17151879; 18350256; 18350256; 18397837; 18489042; 19030707; 19270433; 19953648; 20370853; 20591709; 21314004; 22111599; 23403622 
RAB28	9768	9364	Cone-rod dystrophy 18	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23746546
RAB33B	16075	83452	Dyggve-Melchior-Clausen syndrome; Smith-McCort dysplasia 2	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22652534; 23042644 
RAB39B	16499	116442	Mental retardation, X-linked 72	XL	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11050621; 20159109
RAB3GAP1	17063	22930	Warburg micro syndrome 1	AR	Pediatric		Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	Endocrine; Ophthalmologic; Pharmacogenomic	The condition can include multiple congenital anomalies	The condition can include a risk of glaucoma, and early treatment may be beneficial; Medical care related to endocrine manifestations may be indicated; Agents that may contribute to glaucoma should be avoided	8249951; 10465117; 11237903; 15216543; 15696165; 18286824; 20512159; 22768674 
RAB3GAP2	17168	25782	Warburg micro syndrome 2; Martsolf syndrome 	AR	Pediatric		Cardiovascular; Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	Endocrine; Ophthalmologic; Pharmacogenomic	The condition can include multiple congenital anomalies	The condition can include a risk of glaucoma, and early treatment may be beneficial; Medical care related to endocrine manifestations may be indicated; Agents that may contribute to glaucoma should be avoided	677168; 16532399; 20967465 
RAB7A	9788	7879	Charcot-Marie-Tooth disease, axonal, type 2B	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7573046; 9219740; 11094113; 12545426; 17060578; 22302274 
RAC2	9802	5880	Neutrophil immunodeficiency syndrome	AD	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis (including neutrophil transfusions as part of treatment) and early and aggressive treatment of infections can be beneficial	10758162; 10961859; 21167572 
RAD21	9811	5885	Cornelia de Lange syndrome 	AD	N/A	N/A	Cardiovascular; Craniofacial; Dental; Gastrointestinal; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22633399
RAD50	9816	10111	Breast cancer, susceptibility to	AD	Adult	Allelic with Nijmegen breakage syndrome-like disorder (AR)	Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic	Oncologic		Awareness may allow surveillance, preventive measures, and early diagnosis and treatment of disease	14684699; 16474176; 1887849; 19092773; 19409520; 20571869; 21356067; 21799032; 22006311; 22048815; 22476849; 24549055; 24894818
RAD51	9817	5888	Mirror movements 2	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21242494; 22305526
RAD51C	9820	5889	Breast-ovarian cancer, familial, susceptibility to; Fanconi anemia goup O	AD/AR	Pediatric (Fanconi anemia goup O); Adult (Breast-ovarian cancer, familial, susceptibility to)		Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic; Renal	Allergy/Immunology/Infectious; Hematologic; Oncologic	The condition may include multiple congenital anomalies	In Breast-ovarian cancer susceptibility, surveillance (similar to that indicated in individuals with BRCA1 or BRCA2 mutations) may allow early detection and treatment of tumors, which may reduce morbidity and mortality; For Fanconia anemia, specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; surveillance for complications such as bone marrow failure is recommended	20400964; 20400963; 21568838; 20301575
RAD51D	9823	5892	Ovarian cancer, familial, susceptibility to	AD	Adult		Oncologic	Oncologic		Surveillance (similar to that described for individuals with mutations in BRCA1 or BRCA2) related to ovarian cancer may allow early diagnosis and treatment of neoplasms (eg, ovarian tumors), which may reduce morbidity and mortality; Specific, targeted therapies may be available	21822267; 23300655; 23372765
RAF1	9829	5894	Cardiomyopathy, dilated, 1NN; LEOPARD syndrome 2; Noonan syndrome 5	AD	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Hematologic; Musculoskeletal; Neurologic	Cardiovascular; Hematologic		In Dilated cardiomyopathy, individuals may present in pediatric without other syndromic findings, and awareness may allow early surveillance and management; In LEOPARD and Noonan syndromes, surveillance and treatment related to manifestations such as cardiac anomalies (which include hypertrophic cardiomyopathy) and short stature can be beneficial; Precautions regarding bleeding risk can be beneficial	17603483; 17603482; 20876176; 20602484; 20301303; 24777450
RAG1	9831	5896	T cell-negative, B cell-negative, natural killer cell-positive severe combined immunodeficiency; Omenn syndrome; Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity; Combined cellular and humoral immune defects with granulomas 	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal	Allergy/Immunology/Infectious		Antiinfectious prophylaxis (though special consideration is necessary related to the use of live vaccines) and early and aggressive treatment of infections may be beneficial; HSCT has been reported	9630231; 10226883; 11313270; 16276422; 18463379; 20956421; 20489056; 21131235; 21624848; 21184155; 21732012; 21625022; 21771083; 22424479 
RAG2	9832	5897	Omenn syndrome; Combined cellular and humoral immune defects with granulomas 	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal	Allergy/Immunology/Infectious		Antiinfectious prophylaxis (though special consideration is necessary related to the use of live vaccines) and early and aggressive treatment of infections may be beneficial	9630231; 10226883; 16276422; 20128425; 18463379; 21624848; 21184155; 21625022
RAI1	9834	10743	Smith-Magenis syndrome	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12652298; 15788730; 16845274; 17539903; 21739587; 21897445; 22578325 
RANBP2	9848	5903	Encephalopathy, acute, infection-induced, 3, susceptibility to 	AD	Pediatric		Allergy/Immunology/Infectious; Neurologic	Allergy/Immunology/Infectious		Early diagnosis could allow potentially beneficial measures, such as ensuring up-to-date immunization status (eg, against influenza), though full protection against all inciting agents would not be possible	12874403; 19118815; 19811512; 20473521; 21205700
RAPSN	9863	5913	Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency	AR	Pediatric	Allelic with Fetal akinesia deformation sequence (AR)	Musculoskeletal; Neurologic	Musculoskeletal; Neurologic; Pharmacogenomic		Prophylactic medications (anticholinesterase therapy) in order to prevent apneic episodes/sudden respiratory insufficiency secondary to fever/infections can be effective; Most individuals with CMS benefit from AChE inhibitors and/or  potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; Some individuals with SCCMS are treated with quinidine, which has some major side effects and may be detrimental in individuals with AChR deficiency	1783919; 8041349; 9120223; 9546329; 9668241; 14504330; 12771277; 12651869; 15036330; 9330886; 9498929; 18179903; 20930056; 20301347
RARB	9865	5915	Microphthalmia, syndromic 12	AD/AR	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17506106; 22686418; 24075189
RARS	9870	5917	Leukodystrophy, hypomyelinating 9	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24777941
RARS2	21406	57038	Pontocerebellar hypoplasia, type 6	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17847012; 20635367; 22569581
RASA1	9871	5921	Capillary malformation-arteriovenous malformation; Parkes Weber syndrome; Spinal arteriovenous anomalies	AD	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular		Life-threatening complications of arteriovenous malformations and arteriovenous fistulas can include bleeding, congestive heart failure, and/or neurologic consequences, and surveillance may allow early detection and medical/surgical management, which may decrease morbidity/mortality	14639529; 15917201; 18363760; 18446851; 20007727; 21348050; 20821215; 22342634; 24038909
RASGRP2	9879	10235	Bleeding disorder, platelet-type, 18	AR	Pediatric		Hematologic	Hematologic		Individuals may demonstrate a bleeding diathesis (including postraumatic/postsurgical), and surveillance and prompt treatment of bleeding episodes may be beneficial	24958846
RAX	18662	30062	Microphthalmia, isolated 3	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14662654; 18783408; 22736936
RAX2	18286	84839	Cone-rod dystrophy 11	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15028672
RB1	9884	5925	Retinoblastoma	AD	Pediatric		Oncologic	Oncologic		Frequent and regular eye examination (including under anesthesia if necessary) starting in infancy is indicated in order to detect ocular neoplasms, which may allow early detection and treatment; Awareness of the risk of additional neoplasms may allow early detection and treatment based on signs/symptoms (eg, bone pain); Limiting exposure to DNA-damaging agents (including high-dose radiotherapy) may be beneficial	1066869; 268552; 6930517; 6654325; 6696673; 2876425; 2885916; 2895471; 3175621; 7795591; 8651278; 9311732; 10502774; 10561222; 11097606; 11449317; 11709011; 11382640; 11382638; 12096963; 12523888; 12541220; 12488270; 12598449; 14996857; 16936756; 16631255; 16606893; 17613328; 17096365; 19280657; 20301625; 21150892; 22084214; 22103627; 22237022; 22293180; 22355046 
RB1CC1	15574	9821	Schizophrenia	AD	N/A	N/A	Neurologic	General		Evidence or clinical applicability is unclear	21822266
RBBP8	9891	5932	Seckel syndrome 2; Jawad syndrome	AR	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11781686; 18071751; 21998596; 24389050
RBCK1	15864	10616	Polyglucosan body myopathy, early-onset, with or without immunodeficiency	AR	Pediatric		Allergy/Immunology/Infectious; Cardiovascular; Musculoskeletal; Neurologic	Allergy/Immunology/Infectious; Cardiovascular		Individuals have been described as being affected by recurrent and severe infections, and awareness may allow surveillance, prophylactic measures, and early and aggressive management of infections; Progressive dilated cariomyopathy necessitating heart transplant has been described	23104095; 23798481; 23889995
RBM10	9896	8241	TARP syndrome	XL	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5410571; 20451169; 21910224; 24259342
RBM20	27424	282996	Cardiomyopathy, dilated, 1DD	AD	Pediatric		Cardiovascular	Cardiovascular		Surveillance (eg, with echocardiography and electrocardiography), preventive measures and medical management may help decrease morbidity; Cardiac transplantation has been described	19712804; 20590677; 21846512
RBM28	21863	55131	Alopecia, neurologic defects, and endocrinopathy syndrome	AR	Pediatric		Dermatologic; Endocrine; Musculoskeletal; Neurologic	Endocrine		Features may include progressive endocrine abnormalities primarily related to progressive anterior pituitary hormone deficiency, including central adrenal insufficiency, as well as other endocrine deficiencies, and surveillance in order to allow appropriate hormonal replacement therapy may be beneficial	18439547; 20231366 
RBP3	9921	5949	Retinitis pigmentosa 66	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19074801
RBP4	9922	5950	Retinol dystrophy, iris coloboma, and comedogenic acne syndrome	AR	N/A	N/A	Dermatologic; Ophthalmologic	General	It has been suggested that high-dose vitamin A supplementation may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9888420; 2886863; 1293390; 23189188 
RBPJ	5724	3516	Adams-Oliver syndrome 3	AD	N/A	N/A	Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22883147
RD3	19689	343035	Leber congenital amaurosis 12	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17186464; 20301475; 22531706; 23308101
RDH11	17964	51109	Retinal dystrophy, juvenile cataracts, and short stature syndrome	AR	N/A	N/A	Craniofacial; Neurologic; Musculoskeletal; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24916380
RDH12	19977	145226	Leber congenital amaurosis 13; Retinitis pigmentosa 53	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15258582; 15322982; 16269441; 17197551; 18779497; 19140180; 19840725; 20736127; 22065924 
RDH5	9940	5959	Fundus albipunctatus	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10617778; 10369264; 11153648; 11812441; 16637847; 20829743; 21529959; 22669287; 22736946; 22815624
RDX	9944	5962	Deafness, autosomal recessive 24	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	17226784; 19215054 
RECQL4	9949	9401	Baller-Gerold syndrome; RAPADILINO syndrome; Rothmund-Thomson syndrome	AR	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Oncologic; Renal	Oncologic	The condition may include multiple congenital anomalies	While the disorder may be recognizable, individuals are at risk for neoplasms, and awareness may allow early diagnosis and treatment, which may reduce morbidity and mortality	19990626; 13669699; 7315870; 2801769; 1583650; 8436644; 8737976; 10319867; 10678659; 11045594; 11102924; 11471165; 12838562; 12952869; 12734318; 15964893; 18716613; 20113479; 20503338; 20618321; 21143835; 21872685 
REEP1	25786	65055	Spastic paraplegia 31; Distal hereditary motor neuronopathy VB 	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16826527; 18321925; 19034539; 22703882 
REEP2	17975	51308	Spastic paraplegia 72	AD/AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24388663
RELN	9957	5649	Lissencephaly 2	AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10973257; 17431900
REN	9958	5972	Hyperuricemic nephropathy, familial juvenile 2	AD	Pediatric	Allelic with Hyperproreninemia, familial (AD); Renal tubular dysgenesis (AR)	Renal	Pharmacogenomic; Renal		Surveillance for hematologic (anemia) and renal (hyperuricemia, decreased renal function) disease may be beneficial to allow early medical management; Treatment of low plasma renin activity/low plasma concentration of aldosterone (eg, through management of sodium intake), as well as medical management of hyperkalemia (eg, with fludrocortisones, potassium restriction) may be beneficial, and may be indicated prior to the development of severe chronic kidney disease, though kidney transplantation may be necessary; Treatment of anemia (with erythropoietin) may be effective; Preventive treatment of hyperuricemia (eg, with allopurinol) and medical treatment of gout (eg, with prednisone, colchicines) may be effective; Certain agents should be avoided, including NSAIDS, ACE-inhibitors, dehydration, and specific dietary practices that can exacerbate gout	2017226; 7982942; 12634862; 16116425; 16164624; 19664745; 21084044; 21473025 
RET	9967	5979	Central hypoventilation syndrome, congenital; Multiple endocrine neoplasia, type IIA; Multiple endocrine neoplasia IIB; Medullary thyroid carcinoma, familial; Pheochromocytoma; Hirschsprung disease, susceptibility to 1	AD/AR	Pediatric	Allelic with Renal agenesis (AD)	Endocrine; Gastrointestinal; Neurologic; Oncologic; Renal	Endocrine; Gastrointestinal; Neurologic; Oncologic	In Central hypoventilation syndrome the data are mixed related to causality (eg, one reported patient was later found to have a mutation in a gene with more evidence for involvement in the condition)	Surveillance/early diagnosis for and treatment of associated neoplasms (eg, including thyroidectomy at an early age, and diagnosis and treatment of sequelae of pheochromocytoma) may reduce morbidity and mortality; Due to risk of Hirschsprung disease, awareness of disease risk may allow prompt diagnosis and treatment, decreasing potential morbidity and mortality;  In Central Hypoventilation, early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality	5844561; 4957444; 6047980; 5637238; 4968712; 4386574; 4695886; 1110583; 980061; 1063979; 554522; 3697657; 2904651; 2563193; 8103403; 8094268; 8099202; 7906417; 7977365; 7914213; 7815416; 7911697; 7906866; 7907913; 8114938; 7915165; 7633441; 7581377; 7784092; 7845675; 8825918; 8826440; 8852653; 8757765; 9111992; 9097963; 8981969; 9090527; 9497256; 9506724; 9384613; 9621513; 9824583; 9760196; 10090908; 10528857; 10521317; 10323403; 10458491; 10522989; 10922382; 11103773; 10777380; 10982477; 11739416; 11436122; 11753660; 11238493; 11502806; 11232007; 12116277; 11953745; 12355085; 12214285; 12086152; 11815959; 11932300; 11788682; 12000816; 12466368; 14561794; 14602786; 14600022; 12788868; 15138456; 15240649; 15759212; 16091499; 15829955; 15805159; 15870131; 15741265; 15827097; 16162881; 16205644; 16443855; 17108762; 17167516; 17895320; 16986122; 17898100; 18252215; 18273880; 19469690; 19856714; 20301434; 20598273; 22715565; 23114404
RFT1	30220	91869	Congenital disorder of glycosylation, type In	AR	Pediatric	 	Biochemical; Gastrointestinal; Hematologic; Neurologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	9516657; 10801058; 18313027; 19701946 
RFX5	9986	5993	Bare lymphocyte syndrome, type II	AR	Pediatric		Allergy/Immunology/Infectious; Gastrointestinal	Allergy/Immunology/Infectious		Prophylaxis and early and aggressive treatment of infections can be beneficial; BMT has been reported in Bare lymphocyte syndrome, type II	7744245; 9401005; 10079298; 12368908
RFX6	21478	222546	Pancreatic hypoplasia, intestinal atresia, and gallbladder aplasia or hypoplasia, with or without tracheoesophageal fistula; Martinez-Frias syndrome; Mitchell-Riley syndrome	AR	Pediatric		Endocrine; Gastrointestinal	Endocrine; Gastrointestinal		While the condition may be recognizable, prompt treatment of gastrointestinal (including pancreatic)  issues would be beneficical	10528254; 15592663; 18512226; 19887127; 20148032; 21965172; 22662242; 23914949
RFXANK	9987	8625	MHC class II deficiency	AR	Pediatric		Allergy/Immunology/Infectious; Gastrointestinal	Allergy/Immunology/Infectious		Prophylaxis and early and aggressive treatment of infections can be beneficial; BMT has been reported in Bare lymphocyte syndrome, type II	7951244; 9806546; 11313409; 12618906; 20414676; 21908431 
RFXAP	9988	5994	Bare lymphocyte syndrome, type II	AR	Pediatric		Allergy/Immunology/Infectious; Gastrointestinal	Allergy/Immunology/Infectious		Prophylaxis and early and aggressive treatment of infections can be beneficial; BMT has been reported in Bare lymphocyte syndrome, type II	650344; 7021490; 9118943; 20197681 
RGR	9990	5995	Retinitis pigmentosa 44	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10581022
RGS9	10004	8787	Bradyopsia	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1790747; 14702087; 17826834  
RGS9BP	30304	388531	Bradyopsia	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14702087
RHAG	10006	6005	Anemia, hemolytic, Rh-null, regulator type; Anemia, hemolytic,Rh-Mod type	AR/BG	Pediatric	Variants are associated with RHAG blood group (BG)	Hematologic	Hematologic		Individuals can suffer severe anemia, which can be ameliorated by splenectomy; Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	4628355; 3103426; 8563755; 9746795; 9442063; 9454778; 9915949; 10467273; 11961248; 19744193
RHBDF2	20788	79651	Tylosis with esophageal cancer	AD	Adult		Dermatologic; Gastrointestinal; Oncologic	Oncologic		Surveillance and early detection of and treatment for malignancy may decrease morbidity and mortality; Individuals may be at especially high risk of esophageal cancer with tobacco use	13209063; 8508402; 8666405; 8651714; 22265016
RHCE	10008	6006	Rhesus blood group	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	1824267; 8220426; 9657769
RHO	10012	6010	Retinitis pigmentosa 4; Retinitis punctata albescens; Night blindness, congenital stationary, autosomal dominant 1	AD/AR	N/A	N/A	Ophthalmologic	General	Oral vitamin A may slow retinal degeneration in some forms of retinitis pigmentosa	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2613244; 2137202; 2215617; 2333895; 1882937; 1302614; 1301135; 8512476; 8358437; 7846071; 8841304; 9197578; 9888392; 10980774; 20301590;  20555336; 21174529; 22419850 
RIMS1	17282	22999	Cone-rod dystrophy 7	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9634506; 12659814
RIN2	18750	54453	Macrocephaly, alopecia, cutis laxa, and scoliosis	AR	N/A	N/A	Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19631308; 20424861; 21431621; 23963297;24449201
RIPK4	496	54101	Popliteal pterygium syndrome, lethal type; Bartsocas-Papas syndrome 	AR	N/A	N/A	Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Ophthalmologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4339984; 10925380; 15264293; 23074676; 22197489; 22197488
RIT1	10023	6016	Noonan syndrome 8	AD	Pediatric		Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Oncologic	Cardiovascular; Oncologic		Surveillance and treatment related to  manifestations such as cardiac anomalies (which include pulmonic stenosis and hypertrophic cardiomyopathy as well as congenital heart defects ) can be beneficial; Individuals may be at increased risk for malignancy (a child with ALL has been described), and although specific surveillance may not be warranted, awareness may allow prompt detection and treatment	23791108; 25124994
RLBP1	10024	6017	Newfoundland rod-cone dystrophy; Bothnia retinal dystrophy; Retinitis punctata albescens; Fundus albipunctatus	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10102298; 11176989; 11868161; 14718298; 18344446; 20301590; 21447491; 22551409 
RMND1	21176	55005	Combined oxidative phosphorylation deficiency 11	AR	N/A	N/A	Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18835491; 23022098; 23022099; 25058219
RMRP	10031	6023	Anauxetic dysplasia; Cartilage-hair hypoplasia; Metaphyseal dysplasia without hypotrichosis	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic	Allergy/Immunology/Infectious; Hematologic; Oncologic		There is a wide range of manifestations and severity, and while the disorder may be frequently (though not always) easily clinically recognizable, there is an increased risk reported of  hematologic, immunologic, and oncologic complications, and surveillance and prompt treatment may be beneficial; HSCT has been described	14284412; 3521972; 1743218; 1789294; 1442902; 1290847; 1404295; 8444246; 9809821; 10494084; 10064668; 11207361; 11940090; 16252239; 16097009; 16832578; 18280854; 18698627; 18280853; 19150606; 20375313; 20538026; 21063072; 22420014; 22987807 
RNASEH2A	18518	10535	Aicardi-Goutieres syndrome 4	AR	N/A	N/A	Cardiovascular; Gastrointestinal; Dermatologic; Cardiovascular; Hematologic; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16845400; 17846997; 20301648
RNASEH2B	25671	79621	Aicardi-Goutieres syndrome 2	AR	N/A	N/A	Cardiovascular; Gastrointestinal; Dermatologic; Hematologic; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9706629; 16845400; 20301648; 25243380
RNASEH2C	24116	84153	Aicardi-Goutieres syndrome 3	AR	N/A	N/A	Cardiovascular; Gastrointestinal; Dermatologic; Hematologic; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16845400; 17846997; 20301648
RNASEL	10050	6041	Prostate cancer, hereditary, 1	AD	Adult		Oncologic	Oncologic	Variants may be involved in susceptibility to multiple cancer types	Surveillance and early diagnosis could potentially be beneficial	11799394; 12022038; 12915880; 16054567; 17224235; 18575592
RNASET2	21686	8635	Leukoencephalopathy, cystic, without megalencephaly	AR	Pediatric		Audiologic/Otolaryngologic; Neurologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may  possibly benefit developmental outcomes in some individuals, including speech and language development	9810556; 11589166; 15851732; 19525954
RNF135	21158	84282	Macrocephaly, macrosomia, facial dysmorphism syndrome	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17632510
RNF139	17023	11236	Renal cell carcinoma, clear cell	AD	Pediatric		Oncologic	Oncologic	Genomic disruptions have been reported	Surveillance and early detection of and treatment for malignancy (a number of cancer types have been described, including renal cell cancer and dysgerminoma) may decrease morbidity and mortality	17539022; 19642973 
RNF168	26661	165918	RIDDLE syndrome	AR	Pediatric		Allergy/Immunology/Infectious; Craniofacial; Musculoskeletal; Neurologic; Oncologic	Allergy/Immunology/Infectious; Oncologic	It has been suggested that heterozygotes may demonstrate an increased risk of oncologic processes as well	Individuals have been described with immunodefiency, as well as radiosensitivity, and thus preventive measures and prophylaxis and early and aggressive treatment of infections may be warranted	17940005; 19203578; 21394101 
RNF213	14539	57674	Moyamoya disease 2	AD/AR	Adult		Cardiovascular	Cardiovascular	Individuals with biallelic mutations typically have earlier onset of manifestations	The condition can manifest with transient ischemic attacks, cerebral infarction, and intracranial hemorrhage, and surveillance, preventive measures and early medical treatment may ameliorate/prevent severe sequelae	21048783; 22377813; 22931863 
RNF216	21698	54476	Cerebellar ataxia and hypogonadotropic hypogonadism (Gordon Holmes syndrome)	AR	Pediatric		Endocrine; Neurologic	Endocrine		Individuals have been described with response to medical treatment (eg, exogenous GnRH therapy), though with progressive loss of pituitary function such that response to treatment decreased and was lost later in the course of disease	11932290; 23656588
RNU4ATAC	34016	100151683	Microcephalic osteodysplastic primordial dwarfism, type I (Taybi-Linder syndrome)	AR	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Renal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	934161; 984702; 9800907; 12571786; 21474760; 21474761; 22581640
ROBO2	10250	6092	Congenital anomalies of the kidney and urinary tract	AD	Pediatric		Renal	Renal		Monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function	17357069
ROBO3	13433	64221	Gaze palsy, horizontal, with progressive scoliosis	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15105459; 16525029; 18829051; 19633821; 21592015; 21850172 
ROGDI	29478	79641	Kohlschutter-Tonz syndrome	AR	N/A	N/A	Dental; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4372200; 16411202; 22482807; 22424600
ROM1	10254	6094	Retinitis pigmentosa 7, digenic	Digenic	N/A	N/A	Ophthalmologic	General	Digenic inheritance (with PRPH2) has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8202715; 1684223
ROR2	10257	4920	Robinow syndrome, autosomal recessive; Brachydactyly, type B1	AD/AR	N/A	N/A	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Renal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10932186; 10986040; 10932187; 10700182; 15952209; 17101003; 17256787; 18831060; 19533773; 19461659; 19640924; 20301418; 21496006; 22178368
RP1	10263	6101	Retinitis pigmentosa 1, autosomal dominant; Retinitis pigmentosa 1, autosomal recessive	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1783394; 10391211; 10391212; 18552984; 19933189; 20664799; 21746989; 22052604; 22317909; 22321012; 22917891; 23077400 
RP1L1	15946	94137	Occult macular dystrophy; Retinitis pigmentosa, autosomal recessive	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2774037; 8909203; 10670483; 12664360; 17317401; 20826268; 22466457; 23281133
RP2	10274	6102	Retinitis pigmentosa 2	XL	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9697692; 10053026; 10942419; 11462235; 12417528; 20021257; 20625056; 21738648 
RP9	10288	6100	Retinitis pigmentosa 9	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8513323; 12032732
RPE65	10294	6121	Retinitis pigmentosa 20; Leber congenital amaurosis 2	AR	N/A	N/A	Ophthalmologic	General	Gene therapy has been described in Leber congenital amaurosis 2, with increased effectiveness early	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13616783; 9326941; 9326927; 9501220; 12960219; 14962443; 15557452; 18441371; 18809924; 19675341; 18441370; 18774912; 19854499; 20006823; 22323828; 22644094; 23341016; 23341635; 23474247
RPGR	10295	6103	Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness	XL	Pediatric	Allelic with Cone-rod dystrophy, X-linked, 1 (XL); Macular degeneration, X-linked atrophic (XL); Retinitis pigmentosa 3 (XL)	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Ophthalmologic 	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic	Individuals can have hearing loss, some of which may be attributed to recurrent ear infections	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial: Individuals may demonstrate hearing loss at a relatively young age, and interventions related to recognition and management of hearing impairment may be beneficial	1733835; 7611300; 8673101; 8817343; 9350809; 9399904; 9443860; 10094550; 10970770; 10932196; 12160730; 11857109; 11950860; 11875055; 14627685; 14564670; 12657579; 12920075; 15914600; 16387007; 16055928; 17480003; 21857984; 21866333; 22183348; 24043777
RPGRIP1	13436	57096	Leber congenital amaurosis 6; Cone-rod dystrophy 13	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11283794; 11528500; 12920076; 20006823; 20301475 
RPGRIP1L	29168	23322	Meckel syndrome, type 5; Joubert syndrome 7; COACH syndrome; Retinal degeneration in ciliopathy, modifier of	AD/AR	N/A	N/A	Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Variants may modify severity of BBS and related disorders due to mutations in other BBS-associated genes, as well as Leber congenital amaurosis 1	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17558407; 17558409; 18565097; 19430481; 19574260; 20301500 
RPIA	10297	22934	Ribose 5-phosphate isomerase deficiency	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14988808
RPL11	10301	6135	Diamond-Blackfan anemia 7	AD	Pediatric		Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Oncologic; Renal	Hematologic; Oncologic		Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; Surveillance for and early treatment of malignancy may allow early detection and management; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	16317735; 19061985; 20301769; 23718193; 23812780
RPL15	10306	6138	Diamond-Blackfan anemia 12	AD	Pediatric		Cardiovascular; Hematologic; Musculoskeletal; Neurologic; Oncologic	Hematologic; Oncologic		Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; Surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	20301769; 23812780
RPL21	10313	6144	Hypotrichosis 12	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19751230; 21412954
RPL26	10327	6154	Diamond-Blackfan anemia 11	AD	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Oncologic; Renal	Hematologic; Oncologic		Individuals may manifest with severe, transfusion dependent anemia, as well as profound neutropenia, and medical treatment (eg, with corticosteroids) has been reported as beneficial; Surveillance for and early treatment of malignancy may allow early detection and management; Awareness of the hearing loss may allow early interventions related to speech and language development; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	16317735; 17186470; 18535205; 19061985; 20116044; 20301769; 22431104
RPL35A	10345	6165	Diamond-Blackfan anemia 5	AD	Pediatric		Craniofacial; Hematologic; Oncologic	Hematologic; Oncologic		Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	16317735; 18535205; 20301769; 23812780
RPL5	10360	6125	Diamond-Blackfan anemia 6	AD	Pediatric		Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Oncologic; Renal	Hematologic; Oncologic		Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; Surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	16317735; 5764780; 19061985; 20301769; 23718193; 23812780
RPS10	10383	6204	Diamond-Blackfan anemia 9	AD	Pediatric		Craniofacial; Hematologic; Oncologic	Hematologic; Oncologic		Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; Surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	16317735; 20116044; 20301769;  23812780
RPS17	10397	6218	Diamond-Blackfan anemia 4	AD	Pediatric		Craniofacial; Hematologic; Musculoskeletal; Oncologic	Hematologic; Oncologic		Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; Surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	16317735; 17647292; 19061985; 20301769; 23718193; 23812780
RPS19	10402	6223	Diamond-Blackfan anemia 1	AD	Pediatric		Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Hematologic; Oncologic		Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	13722603; 16317735; 276838; 273451; 1958491; 8826887; 9988267; 10541318; 10590074; 16741228; 19061985; 20301769; 23812780; 23812780
RPS24	10411	6229	Diamond-Blackfan anemia 3	AD	Pediatric		Cardiovascular; Craniofacial; Hematologic; Oncologic	Hematologic; Oncologic		Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	16317735; 17186470; 20301769
RPS26	10414	6231	Diamond-Blackfan anemia 10	AD	Pediatric		Craniofacial;Hematologic; Musculoskeletal; Oncologic	Hematologic; Oncologic		Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	16317735; 20116044; 20301769
RPS29	10419	6235	Diamond-Blackfan anemia 13	AD	Pediatric		Cardiovascular; Hematologic; Oncologic	Hematologic; Oncologic		Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; BMT has been described	24829207
RPS6KA3	10432	6197	Coffin-Lowry syndrome; Mental retardation, X-linked 19	XL	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Neurologic	Audiologic/Otolaryngologic; Cardiovascular; Neurologic		The condition can include premature death from cardiovascular complications, including cardiomyopathy, and surveillance (including with echocardiogram and electrocardiogram) may allow early medical management ; The condition may include hearing deficits, and surveillance may be beneficial; Medical management of stimulus-induced drop attacks (eg, with valproate, clonazepam, or SSRIs) may be beneficial, as are measures to prevent injuries from related falls	5581017; 5052411; 1133653,; 146889; 7681250; 7943043; 9719387; 9832033; 9744638; 10528858; 10319851; 11160957; 12210291; 15214012; 16879200; 17100996; 17318637; 19888300; 20301520; 20637903; 21614984; 22009732; 22490425 
RPS7	10440	6201	Diamond-Blackfan anemia 8	AD	Pediatric		Craniofacial; Hematologic; Oncologic	Hematologic; Oncologic		Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	16317735; 19061985; 20301769; 23718193; 23812780
RPSA	6502	3921	Asplenia, isolated congenital	AD	Pediatric		Allergy/Immunology/Infectious; Gastrointestinal	Allergy/Immunology/Infectious		Individuals are susceptible to severe bacterial infections in early life, and awareness may allow prophylaxis and early and aggressive management of infections	20846672; 23579497
RRM2B	17296	50484	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 5; Mitochondrial DNA depletion syndrome 8A; Mitochondrial DNA depletion syndrome 8B	AD/AR	N/A	N/A	Biochemical; Gastrointestinal; Musculoskeletal; Neurologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17486094; 19667227; 19138848; 19664747 
RS1	10457	6247	Retinoschisis 1, X-linked, juvenile	XL	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9326935;  9618178; 10636740; 10533068; 10922205; 10636421; 15531314; 15937075; 17304551; 17172462; 17296904; 20061330
RSPH1	12371	89765	Ciliary dyskinesia, primary, 24	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Genitourinary; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial	20301301; 23993197; 24518672
RSPH4A	21558	345895	Ciliary dyskinesia, primary, 11	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary	19200523; 20301301
RSPH9	21057	221421	Ciliary dyskinesia, primary, 12	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Genitourinary;  Pulmonary	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary	19200523; 20301301
RSPO1	21679	284654	Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and 46,XX sex reversal	AR	Adult		Audiologic/Otolaryngologic; Dermatologic; Endocrine; Genitourinary; Oncologic; Ophthalmologic	Genitourinary; Oncologic 		Surveillance/treatment of gonadal tumors and specific malignancies may improve outcome	17041600; 18085567
RSPO4	16175	343637	Anonychia/hyponychia congenita	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4702713; 17186469; 17041604; 17914448; 18070203; 22300369 
RTEL1	15888	51750	Dyskeratosis congenita, autosomal dominant 4 (AD); Dyskeratosis congenita, autosomal recessive, 5 (AR)	AD/AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic;  Oncologic; Pulmonary	Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary		Affected individuals have been described with a number of hematopoietic manifestations, including anemia and thrombocytopenia, and have frequently been reported as suffering from bone marrow failure; Individuals may be at increased risk of oncologic processes, and awareness may allow early detection and treatment; HSCT has been described	19461895; 23329068; 23453664; 23591994; 23959892
RTN2	10468	6253	Spastic paraplegia 12, autosomal dominant	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10677333; 12427890; 22232211
RTTN	18654	25914	Polymicrogyria with seizures	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22939636
RUNX1	10471	861	Platelet disorder, familial, with associated myeloid malignancy	AD	Pediatric		Hematologic; Oncologic	Hematologic; Oncologic		Individuals can have thrombocytopenia and bleeding episodes (eg, associated with surgical procedures), and awareness may allow preventive measures as well as prompt treatment; There is a reported increased risk of malignancy (such as acute myelogenous leukemia), and awareness may allow surveillance measures enabling early detection and management, which may be beneficial; BMT has been reported	10508512; 11830488; 18478040; 19357396; 19387465; 20846103; 22571758 
RUNX2	10472	860	Cleidocranial dysplasia; Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly	AD	N/A	N/A	Craniofacial; Dental; Musculoskeletal	General	Duplications including the gene have also been reported as resulting in additional skeletal anomalies such as craniosynostosis	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14818746; 2301472;  9182765; 10545612; 11746020; 12424590; 16222673; 15952089; 20301686; 20683987; 21734816; 22023169; 22194205; 23220435; 23290074; 23348268; 23558979; 23659235
RXFP2	17318	122042	Cryptorchidism	AD	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12217959; 12970298
RYR1	10483	6261	Malignant hyperthermia, susceptibility 1; Central core disease; Minicore myopathy; Multicore myopathy; Minicore myopathy with external ophthalmoplegia; Centronuclear myopathy (individuals with these conditions may also be at risk of malignant hyperthermia)	AD/AR	Pediatric		Cardiovascular; Musculoskeletal; Renal	Cardiovascular; Musculoskeletal; Renal; Pharmacogenomic		Individuals with recessive inheritance have been described; Invididuals are susceptible to malignant hyperthermic crisis (which can affect both skeletal muscle and cardiac function) in a number of situations, including when exposed to specific agents such as certain agents used in anesthesia (eg, halothane) or depolarizing muscle relaxants (eg, succinyl choline), and to treat or prevent acute crises, dantrolene can be effective; Individuals may also suffer from exertional rhabdomyolysis or have attacks triggered by tachycardia or acidosis, and precautions may be beneficial;  For: Central core disease; Minicore myopathy; Multicore myopathy; Minicore myopathy with external ophthalmoplegia; Centronuclear myopathy, individuals with these conditions may also be at risk of malignant hyperthermia, and appropriate precautions may be beneficial	13396066; 637752; 7362206; 7299413; 6348539; 1774074; 8220423; 8220422; 9199552; 9497245; 10097181; 11113224; 11389482; 11448278; 12112081; 12136074; 12467748; 12719381; 14732627; 16380615; 16163667; 16084090; 17190947; 17376685; 18253926; 17538032; 19303294; 19734047; 19807743; 20301565; 20301325; 20839240 
RYR2	10484	6262	Ventricular tachycardia, catecholaminergic polymorphic, 1; Arrhythmogenic right ventricular dysplasia 2  	AD	Pediatric		Cardiovascular	Cardiovascular		Mortality is high in untreated Ventricular tachycardia, catecholaminergic polymorphic, 1, and treatment (eg, beta-blockers without sympathomimetic activity) can be effective to reduce syncope, but ICD placement may be needed; In ARVD2, individuals may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation 	11157710; 11208676; 11159936; 17875969; 20301310; 19926015
SACS	10519	26278	Spastic ataxia, Charlevoix-Saguenay type	AR	N/A	N/A	Cardiovascular; Musculoskeletal;  Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10655055; 12873855; 14718706; 14718708; 15985586; 18398442; 20876471; 21745802; 21993619; 22209141; 22892508 
SAG	10521	6295	Retinitis pigmentosa 47; Oguchi disease 1	AR	N/A	N/A	Ophthalmologic	General		Manifesting heterozygotes have been described; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7670478; 9565049; 21447990; 21494281; 21987685; 22665972 
SALL1	10524	6299	Townes-Brocks syndrome	AD	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Renal	Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Renal	The condition may be recognizable due to the presence of a specific pattern of congenital malformations affecting hearing as well as multiple organ systems	While frequently recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Surveillance for manifestations affecting other organ systems (eg, cardiac, endocrine, and renal) may allow early intervention, potentially reducing morbidity and mortality	5042490; 9072124; 9425907; 10928856; 11484202; 14755477; 16088922; 8000979; 17431915; 20301618 
SALL2	10526	6297	Ocular coloboma	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24412933
SALL4	15924	57167	Duane-radial ray/Okohiro syndrome; Acro-Renal-Ocular syndrome	AD	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Ophthalmologic; Renal	Audiologic/Otolaryngologic; Renal	The conditions can include multiple congenital anomalies	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with vesicoureteral reflux, and surveillance and management may be helpful to preserve renal function	843249; 7395922; 12395297; 11826030; 12393809; 12789647; 12843316; 12868480; 15342710; 16086360; 16402211; 16411190; 17256792; 20301547 
SAMD9	1348	54809	Tumoral calcinosis, normophosphatemic	AR	Pediatric		Allergy/Immunology/Infectious; Dental; Dermatologic; Musculoskeletal; Ophthalmologic	Allergy/Immunology/Infectious; Musculoskeletal		Surveillance/early treatment of tumoral calcinosis may reduce morbidity	3366131; 15133511; 16960814; 18094730 
SAMHD1	15925	25939	Aicardi-Goutieres syndrome 5	AR	Pediatric	Allelic with Chilblain lupus 2 (AD)	Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Neurologic	Cardiovascular		For Aicardi-Goutieres syndrome related to mutations in SAMHD1, it has been suggested that individuals should be actively screened for intracranial arteriopathy in order to allow prompt intervention, which may reduce morbidity and mortality	19525956; 20301648; 20358604; 20653736; 20842748; 21102625; 21402907; 21204240; 21633013; 22149989
SAR1B	10535	51128	Chylomicron disease (Anderson disease)	AR	Pediatric		Gastrointestinal; Musculoskeletal; Neurologic	Gastrointestinal		Individuals typically present in infancy with with steatorrhea and failure to thrive, and dietary measures (maintenance of adequate caloric intake on a low-long chain fat diet consisting of polyunsaturated fatty acids, with supplementation of lipid soluble vitamins, including large amounts of vitamin E, and essential fatty acids) can be beneficial 	2426307; 3792776; 7601203; 10521380; 10665502; 12692552; 17309654; 20920215 
SARS2	17697	54938	Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis	AR	N/A	N/A	Endocrine; Neurologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21255763
SART3	16860	9733	Porokeratosis, disseminated superficial actinic, 1	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15840095
SATB2	21637	23314	Cleft palate and mental retardation (Glass syndrome)	AD	N/A	N/A	Craniofacial; Dental; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17377962; 19170718; 19668335; 22521361; 23925499; 24301056; 24363063
SBDS	19440	51119	Shwachman-Diamond syndrome; Aplastic anemia	AD/AR	Pediatric		Allergy/Immunology/Infectious; Gastrointestinal; Hematologic; Musculoskeletal; Oncologic	Allergy/Immunology/Infectious; Gastrointestinal; Hematologic; Oncologic	Heterozygous mutations can result in incompletely penetrant aplastic anemia	In Aplastic anemia, surveillance and prompt treatment of aplastic anemia and bone marrow failure, as well as associated myelodysplasia, which has been reported, may reduce morbidity; BMT and HSCT have been reported; In Shwachman-Diamond syndrome, medical treatment (eg, pancreatic enzymes, fat-soluble vitamins) can be effective to treat pancreatic exocrine insufficiency; Blood/platelet transfusions may be necessary; Due to neutropenia and infectious risk, G-CSF and other prophylactic measures (eg antibiotics), as well as early and aggressive treatment of infections, may be beneficial, but prolonged use of agents such as G-CSF may have adverse effects; Regular surveillance for hematologic anomalies is recommended; Awareness of the risk of malignant transformation may allow early detection and management; HSCT use has been reported	14221166; 7264801; 8942739; 8759887; 9359520; 10467990; 10393609; 12183725; 12496757; 14984468; 15769891; 17376717; 17400792; 17478638; 17916435; 20301722; 22554078; 22992231; 23305959; 23351992
SBF1	10542	6305	Charcot-Marie-Tooth disease, type 4B3	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21210780; 23749797; 24799518
SBF2	2135	81846	Charcot-Marie-Tooth disease, type 4B2 with early-onset glaucoma	AR	Pediatric		Audiologic/Otolaryngologic; Neurologic; Ophthalmologic	Ophthalmologic; Pharmacogenomic	Several families with CMT4B2 with early-onset glaucoma have been reported; One report has also described homozygous variants associated with Congenital thrombocytopenia, autosomal recessive	Open-angle glaucoma is typically asymptomatic until  late stages, when irreversible  nerve damage has already taken place; As the condition may include early-onset hearing loss, intervention related to speech and language development may be beneficial; Agents that may contribute to glaucoma should be avoided	9521281; 10932274; 12687498; 12554688; 15477569; 15304601; 23334996 
SC5D	10547	6309	Lathosterolosis	AR	N/A	N/A	Biochemical; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic	General	The condition can involve multiple congenital anomalies; Lipid storage has been reported as being aggravated by supplemental cholesterol	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12189593; 12812989; 17853487; 19123163 
SCARB2	1665	950	Epilepsy, progressive myoclonic 4, with or without renal failure	AR	N/A	N/A	Cardiovascular; Neurologic; Renal	General	In addition to other manifestations, renal dysfunction and cardiomyopathy have been reported; Renal transplant has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15364701; 17030781; 18424452; 18308289; 19847901; 21782476; 21670406; 22032306; 22050460; 22767442 
SCARF2	19869	91179	Van den Ende-Gupta syndrome	AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20887961; 23808541
SCN11A	10583	11280	Episodic pain syndrome, familial, 3	AD	N/A	N/A	Neurologic	General	The pain has been reported as responsive to oral anti-inflammatory analgesics	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24207120; 24776970
SCN1A	10585	6323	Migraine, familial hemiplegic 3	AD	Pediatric	Allelic with Early infantile epileptic encephalopathy 6 (AD); Generalized epilepsy with febrile seizures plus, type 2 (AD), Febrile seizures, familial 3A (AD)	Neurologic	Neurologic; Pharmacogenomic		Vasoconstricting agents (due to risk of stroke) and cerebral angiograophy (due to risk of precipitation of attack) should be avoided	10486327; 10852559; 10742094; 11524484; 15277634; 16054936; 16326807; 16505326; 17190949; 17347258; 20301562; 19522081; 19332696
SCN1B	10586	6324	Atrial fibrillation, familial 13; Brugada syndrome 5	AD	Pediatric	Allelic with Generalized epilepsy with febrile seizures plus, type 1 (AD)	Cardiovascular; Neurologic	Cardiovascular; Pharmacogenomic		In Atrial fibrillation, surveillance (eg, with echocardiogram and electrocardiogram) may allow early medical and/or surgical management (eg, atrioventricular nodal ablation followed by dual-chamber pacemaker implantation has been described), which may be beneficial; In Brugada syndrome, surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial;  Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever	9697698; 12011299; 14504340; 18464934; 19808477; 20301690
SCN2A	10588	6326	Epileptic encephalopathy, early infantile, 11; Seizures, benign familial infantile, 3	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6660252; 3508699; 8734025; 11326335; 15048894; 15028761; 19786696; 20956790; 22029951; 22591750; 22612257; 23020937 
SCN2B	10589	6327	Atrial fibrillation, familial 14	AD	Adult		Cardiovascular	Cardiovascular		In Atrial fibrillation, surveillance (eg, with echocardiogram and electrocardiogram) may allow early management, which may be beneficial	19808477
SCN3B	20665	55800	Brugada syndrome 7; Atrial fibrillation, familial 16	AD	Adult		Cardiovascular	Cardiovascular; Pharmacogenomic		In Atrial fibrilliation, medical/preventive management may decrease morbidity; In Brugada syndrome, surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial; Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever	20031595; 20301690; 20558140; 21051419
SCN4A	10591	6329	Paramyotonia congenita; Hyperkalemic periodic paralysis, type 2; Hypokalemic periodic paralysis, type 2; Normokalemic potassium-sensitive periodic paralysis; Malignant hyperthermia, susceptibility to; Myasthenic syndrome, congenital, acetazalomide-responsive (AR); Myotonia, potassium-aggravated	AD/AR	Pediatric		Cardiovascular; Musculoskeletal; Neurologic	Cardiovascular; Musculoskeletal; Neurologic; Pharmacogenomic	Clinically, allelic conditions have been divided into different forms of the disorder: paramyotonia, potassium-aggravated myotonia, and periodic paralysis; Potassium-aggravated myotonia includes mild myotonia fluctuans, severe myotonia permanens, and acetazolamide-responsive myotonia	In hypokalemic disease, treatment, such as potassium supplementation can be effective; Acetazolamide treatment is beneficial in the majority (including with normokalemic and hyperkalemic disease), but in a lower proportion of mutation-negative patients; Individuals can have cardiac complications, including sudden cardiac death; In Paramyotonia congenita, medications (eg, mexilitene, carbamazepine, phenytoin) may be effect in some individuals, and avoidance and specific preciptating circumstances may be beneficial; Myotonia, potassium-aggravated can be aggravated by potassium and fasting, and effectively treated with medications (eg, acetazolamide, carbamazepine, mexilitene); In Malignant hyperthermia, early diagnosis, discontinuation of potent inhalation agents/succinylcholine, treatment of metabolic abnormalities, and administration of dantrolene sodium intravenously are essential to  treat acute MH; In Myasthenic syndrome, congenital, acetazalomide-responsive, pyridostigmine can improve endurance; Acetazolamide can prevent further attacks of respiratory and bulbar weakness	13544644; 13758355; 13963901; 13946346; 14090531; 5828532; 14237771; 673408; 852462; 4022357; 3587272; 2396930; 1654742; 1310898; 1338909; 1316765; 8424309; 8385748; 8242056; 8308722; 8058156; 7741283; 9131651; 9131654; 10599760; 10369308; 10930446; 10727489; 12933953; 12766226; 15534250; 15557532; 15596759; 15642860; 16832098; 16786525; 17998485; 18203179; 19015492; 19015483; 18337100; 19118277; 20237798; 20301512; 20301669; 20713951; 21220685; 22617007; 23460624; 23516313; 23771340; 23801527; 23958773; 24082935
SCN4B	10592	6330	Long QT syndrome 10; Atrial fibrilliation, familial 17	AD	Pediatric		Cardiovascular	Cardiovascular		In Atrial fibrillation and Long QT syndrome, surveillance and medical and/or surgical management related to arrhythmias may be helpful to help decrease morbidity	17592081; 20301308; 23604097
SCN5A	10593	6331	Atrial fibrillation, familial 10; Long QT syndrome 3; Idiopathic ventricular fibrillation; Heart block, progressive, type IA; Heart block, nonprogressive; Sick sinus syndrome 1, autosomal recessive; Cardiomyopathy, dilated, 1E; Brugada syndrome 1	AD/AR/Digenic	Pediatric		Cardiovascular	Cardiovascular; Pharmacogenomic	The inheriatance of conditions such as LQTS and Atrial standstill may involve digenic inheritance involving other genes, such as GJA5	In Atrial fibrilliation, medical/preventive management may decrease morbidity; In Sick sinus syndrome, in pediatric patients, treatment of associated exercise intolerance, presyncope or syncope, typically requires lifelong cardiac pacing; For dysrhthymia-related phenotypes, surveillance and preventive/treatment measures (eg, in LQTS3: beta-blockers, pacemakers, or ICD; In CMD1E: permanent pacing is required in most individuals; Brugada syndrome: ICDs) can decrease morbidity/mortality; For progressive/nonprogressive heart block, surveillance can allow timely treatment (eg, with pacemaker);  Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever	3953067;  8541846; 7889574; 9521325; 10590249; 10471492; 10940383; 10911008; 11748104; 11901046; 11823453; 14523039; 12574143; 12522116; 15466643; 15051636; 15671429; 15840476; 16922724; 16453024; 17038146; 18599870; 18378609; 19122847; 18451998; 18503232; 20025708; 20301690 
SCN8A	10596	6334	Cognitive impairment with or without cerebellar ataxia; Epileptic encephalopathy, early infantile, 13	AD	N/A	N/A	Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16236810; 22365152; 24888894; 25239001
SCN9A	10597	6335	Paroxysmal extreme pain disorder	AD/AR	Pediatric	Allelic with Small fiber neuropathy (AD);  Erythermalgia, primary (AD); Insensitivity to pain, channelopathy-associated (AR)	Dermatologic; Neurologic	Neurologic	Many treatments have been attempted (with inconsistent success) in Erythermalgia, primary, and some have been described by patients as providing subjective relief from symptoms; Congenital insensitivity to pain can result in injuries, some of which may in theory be preventable with early diagnosis and preventive measures	In Primary erythermalgia, medical treatment (with specific sodium channel blocking agents such as XEN402) has been reported as beneficial; Individuals with Paroxysmal extreme pain disorder have been reported as responding to medical therapy (eg, carbamazepine) in terms of clinical manifestations (attacks of pain) as well as psychomotor development in some	13636703; 4111621; 4112340; 1536168; 10724194; 14985375;  15958509; 16216943; 17167479; 17145499; 17679678; 17470132; 19304393; 19763161; 21441906; 21698661; 22035805; 23596073; 24817410
SCNN1A	10599	6337	Pseudohypoaldosteronism, type I; Bronchiectasis with or without elevated sweat chloride 2	AR/Digenic (with CFTR or other SCCN1 genes)	Pediatric		Allergy/Immunology/Infectious; Pulmonary; Renal	Allergy/Immunology/Infectious; Pulmonary; Renal		In Pseudohypoaldosteronism, type I, treatment with electrolyte replacement and control of hyperkalemia can be effective; In Bronchiectasis with or without elevated sweat chloride 2, as in cystic fibrosis, early and aggressive pulmonary and other management (eg, related to prophylaxis and management of respiratory infections) may decrease morbidity	8589714; 9654209; 10202170; 9462466; 19017867
SCNN1B	10600	6338	Pseudohypoaldosteronism, type I; Liddle syndrome; Bronchiectasis with or without elevated sweat chloride 3	AR/Digenic (with CFTR or other SCCN1 genes)	Pediatric		Allergy/Immunology/Infectious; Pulmonary; Renal	Allergy/Immunology/Infectious; Pulmonary; Renal		In Liddle syndrome, certain medications (eg, amiloride, triamterene, but not spironolactone) and dietary sodium restriction can effectively treat hypertension and hypokalemia; In Pseudohypoaldosteronism, type I, treatment with electrolyte replacement and control of hyperkalemia can be effective; In Bronchiectasis with or without elevated sweat chloride 1, as in cystic fibrosis, early and aggressive pulmonary and other management (eg, related to prophylaxis and management of respiratory infections) may decrease morbidity	7046191; 6262354; 3550146; 264740; 7954808; 8524790; 8589714; 10202170; 16207733; 18507830; 19017867
SCNN1G	10602	6340	Pseudohypoaldosteronism, type I; Liddle syndrome; Bronchiectasis with or without elevated sweat chloride 3	AR/Digenic (with CFTR or other SCCN1 genes)	Pediatric		Allergy/Immunology/Infectious; Pulmonary; Renal	Allergy/Immunology/Infectious; Pulmonary; Renal		In Liddle syndrome, certain medications (eg, amiloride, triamterene, but not spironolactone) and dietary sodium restriction can effectively treat hypertension and hypokalemia; In Pseudohypoaldosteronism, type I, treatment with electrolyte replacement and control of hyperkalemia can be effective; In Bronchiectasis with or without elevated sweat chloride 3, as in cystic fibrosis, early and aggressive pulmonary and other management (eg, related to prophylaxis and management of respiratory infections) may decrease morbidity	7046191; 3550146; 3550146; 7550319; 8640238; 9649551; 10202170; 18507830; 19017867
SCO1	10603	6341	Mitochondrial complex IV deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Attention deficit-hyperactivity disorder, susceptibility to refers to a susceptibility locus and/or evidence or clinical applicability unclear	11013136; 22231385
SCO2	10604	9997	Myopia 6; Leigh syndrome; Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1; Hypertrophic cardiomyopathy	AD/AR	N/A	N/A	Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	General	In addition to other manifestations, hypertrophic cardiomyopathy has been reported in individuals with bi-allelic mutations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10545952; 10749987; 12538779; 15210538; 18924171; 22231385; 23364397; 23643385
SCP2	10606	6342	Leukoencephalopathy with dystonia and motor neuropathy	AR	N/A	N/A	Biochemical; Endocrine; Genitourinary; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16685654
SDCCAG8	10671	10806	Bardet-Biedl syndrome 16; Senior-Loken syndrome 7	AR	N/A	N/A	Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Renal transplant has been described; The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20835237; 22626039
SDHA	10680	6389	Paragangliomas 5; Gastrointestinal stromal tumors; Cardiomyopathy, dilated, 1GG; Leigh syndrome/Mitochondrial respiratory chain complex II deficiency	AD/AR	Adult (Paragangliomas 5; Gastrointestinal stromal tumors); Pediatric (Cardiomyopathy, dilated, 1GG; Leigh syndrome/Mitochondrial respiratory chain complex II deficiency)	Allelic with Cardiomyopathy, dilated, 1GG (AR); Leigh syndrome/Mitochondrial respiratory chain complex II deficiency (AR)	Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Oncologic	Biochemical; Gastrointestinal; Oncologic	In mitochondrial disease, such as Dilated cardiomyopathy, recognition of cardiovascular disease may allow early medical management, which may be helpful to help decrease morbidity; In Leigh syndrome/Mitochondrial respiratory chain complex II deficiency,  medical treatment (eg, with riboflavin, uniquinol) may be beneficial, and individuals may have cardiac involvement such that surveillance may be beneficial	For Parangangliomas, symptoms are reported as resolving after surgical tumor resection; For Gastrointestinal stromal tumors, surveillance may allow early diagnosis and treatment, which may improve outcomes; In mitochondrial disease, such as Dilated cardiomyopathy, recognition of cardiovascular disease may allow early medical management, which may be helpful to help decrease morbidity; In Leigh syndrome/Mitochondrial respiratory chain complex II deficiency,  medical treatment (eg, with riboflavin, uniquinol) may be beneficial, and individuals may have cardiac involvement such that surveillance may be beneficial	7550341; 10746566; 12794685; 16737791; 16798039; 20484225; 20551992; 21505157; 22972948
SDHAF1	33867	644096	Mitochondrial complex II deficiency	AR	Pediatric	N/A	Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	Biochemical		Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may multisystemic, including cardiac, involvemen (which can include arrhythmias), and surveillance and early interventions may be beneficial	12112045; 16737791; 19465911; 22995659 
SDHAF2	26034	54949	Paragangliomas 2	AD	Pediatric		Oncologic	Oncologic		Surveillance/early treatment of tumors (eg, surgical resection) can be effective	6286462; 19628817; 20071235; 21348866; 20301715; 21224366; 22584701; 23061808; 23078982 
SDHB	10681	6390	Cowden-like syndrome; Paraganglioma and gastric stromal sarcoma; Gastrointestinal stromal tumor; Pheochromocytoma; Paragangliomas 4	AD	Pediatric		Oncologic	Oncologic	The proof for causation related to Cowden syndrome is unclear	Surveillance for and early diagnosis/treatment of  associated neoplasms can be beneficial	490809; 11404820; 12000816; 12213855; 12364472; 14500403; 15479192; 15328326; 14685938; 16317055; 17102084; 16522703; 17652212; 17848412; 17804857; 17200167; 18057081; 17667967; 18678321; 19251979; 19351833; 19576851; 20301715; 20503330; 21366490; 21565294; 21348866; 22328163
SDHC	10682	6391	Paraganglioma and gastric stromal sarcoma; Gastrointestinal stromal tumor; Paragangliomas 3	AD	Pediatric		Oncologic	Oncologic		Surveillance/early treatment of neoplasms may improve outcomes	15342702; 15342702; 16249420; 17804857; 17667967; 21173220; 21348866; 22703879 
SDHD	10683	6392	Cowden syndrome 3; Paraganglioma and gastric stromal sarcoma; Pheochromocytoma; Paragangliomas; Carcinoid tumors, intestinal	AD	Pediatric		Oncologic	Oncologic		Surveillance for and early diagnosis/treatment of  associated neoplasms can be beneficial	10657297; 11156372; 11526495; 11343322; 11519521; 12000816; 12205103; 12111639; 12007193; 12811540; 15032977; 15479192; 15328326; 16317055; 17848412; 17804857; 17667967; 18678321; 19239085; 19584903; 21348866; 21565294; 22261759; 22948026; 23072324; 23099648
SEC23A	10701	10484	Craniolenticulosutural dysplasia	AR	N/A	N/A	Craniofacial; Musculoskeletal; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12677423; 16980979; 21039434 
SEC23B	10702	10483	Anemia, dyserythropoietic congenital, type II	AR	Pediatric		Gastrointestinal; Hematologic	Gastrointestinal; Hematologic	Heterozygotes may have mild manifestations	Individuals may require RBC transfusions in the neonatal period; Splenectomy may be beneficial; Gallbladder complications are common, and early treatment may be beneficial; Iron overload is common	13884336; 5807784; 5807786; 4340898; 10753261; 11493480; 19621418; 19561605; 20381388; 20941788;21252497; 21378561; 21850656; 22208203; 22428539; 23065504; 23453696; 23940284; 23978024; 24196372
SEC63	21082	11231	Polycystic liver disease	AD	N/A	N/A	Gastrointestinal	General	Though some individuals may require treatment, it is unclear if early (genetic) diagnosis would be beneficial; Liver transplantion has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15133510; 22099398; 23209713 
SECISBP2	30972	79048	Selenoprotein deficiency	AR	N/A	N/A	Audiologic/Otolaryngologic; Endocrine; Musculoskeletal; Neurologic	General	Findings, such as growth retardation, may be transient, and the overall phenotypic range has been described as wide	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16228000; 19265499; 19602558; 19769464; 20501692; 20685891; 21084748; 21511232; 22247018; 22986150
SEMA3A	10723	10371	Hypogonadotropic hypogonadism 16 with or without anosmia	AD	Pediatric		Endocrine; Genitourinary; Neurologic	Endocrine	Surveillance in adolescence related to sexual maturation is indicated, and in order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to  fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	Surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to  fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	22416012
SEMA3E	10727	9723	CHARGE syndrome	AD	N/A	N/A	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition can include multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11241468; 15235037
SEMA4A	10729	64218	Cone-rod dystrophy 10; Retinitis pigmentosa 35	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16199541
SEMA7A	10741	8482	Blood group, John Milton Hagen	AD	Pediatric	 	Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	17207242; 20854351
SEPN1	15999	57190	Muscular dystrophy, rigid spine, 1; Myopathy, congenital, with fiber-type disproportion	AR	N/A	N/A	Musculoskeletal	General	Cardiac involvement has been described in some individuals	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7224095; 11528383; 12192640; 15122708; 16365872; 20301436; 20301467; 21670436
SEPSECS	30605	51091	Pontocerebellar hypoplasia, type 2D	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12920088; 20920667
SEPT12	26348	124404	Spermatogenic failure 10	AD	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22275165; 22479503
SEPT9	7323	10801	Amyotrophy, hereditary neuralgic	AD	N/A	N/A	Craniofacial; Neurologic	Neurologic		It has been reported that medical treatment (eg, with corticosteroids) may prevent attacks of brachial plexus neuropathy  during specific situations, such as during surgery and in childbirth	11739810; 16186812; 18492087; 19451530; 19939853; 20301569; 23042485  
SERAC1	21061	84947	3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome 	AR	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Neurologic 	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16527507; 22683713; 23707711
SERPINA1	8941	5265	Alpha-1-Antitrypsin deficiency	AR	Pediatric		Gastrointestinal; Pulmonary	Gastrointestinal; Pulmonary		Medical treatment (augmentation therapy  with purified alpha-1-antitrypsin, Vitamin E supplementation) can be helpful for pulmonary and hepatic manifestations; Exacerbating factors (eg, smoking) should be avoided; Liver transplantation may be necessary in individuals with severe liver manifestations	4240153; 4117022; 3494198; 2185272; 2035327; 7875269; 8066566; 10898319; 12740257; 11320399; 12452881; 12574076; 14522813; 15282394; 15214923; 20301692; 21457231; 21752289; 22016686; 22215832; 22330941; 22500781; 22536580; 22933512; 23055718; 23251618; 23766346
SERPINA6	1540	866	Corticosteroid-binding globulin deficiency	AD/AR	N/A	N/A	Endocrine	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7061486; 8212073; 10634411; 11502797; 17245537; 20610591; 22013108; 22337907; 22948765 
SERPINA7	11583	6906	Thyroxine-binding globulin deficiency; Thyroxine-binding globulin excess	XL	N/A	N/A	Endocrine	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8530630; 11600582; 11889160; 19415532 
SERPINB6	8950	5269	Deafness, autosomal recessive 91	AR	N/A	N/A	Audiologic/Otolaryngologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20451170; 24963352
SERPINB7	13902	8710	Palmoplantar keratoderma, Nagashima type	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24207119; 24773080
SERPINC1	775	462	Antithrombin III deficiency	AD/AR	Pediatric		Hematologic	Hematologic	The inheritance depends on specific variant	Individuals may be at high risk for thromboembolism, and recognition may allow preventive/prophylactic measures as well as prompt treatment of thromboembolic and related manifestations, including medical treatment with antithrombin, and chronic anticoagulations, which is indicated in asymptomatic individuals as well as those who have previously suffered sequelae 	14347873; 6582486; 3055413; 3350974; 1868237; 2146503; 1671110; 8091378; 16705712; 18208532; 19760264; 21655678; 21655682; 21240680; 21325262; 22997155; 22961244 
SERPIND1	4838	3053	Heparin cofactor II deficiency	AD	N/A	N/A	Hematologic	General	Individuals may be at higher risk for thrombophilia, though data are controversial, and may be clinically relevant only in the presence of another thrombophilia-related variant	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2863444; 3603411; 2647747; 1615493; 8902986; 8562924; 9607121; 10650845; 10494755; 12421148; 15337701 
SERPINE1	8583	5054	Plasminogen activator inhibitor-1 deficiency	AR	Pediatric		Hematologic	Hematologic		Individuals are susceptible to bleeding related to situations such as traumatic injury or surgery, and females manifest with menorrhagia, and precautions may be helpful to avoid severe sequelae; Medical treatment (eg, with fibrinolysis inhibitors) have been reported as beneficial in the prevention and treatment of bleeding episodes	2496147; 1435917; 9207454; 10754381; 15650551; 20664190; 21486382 
SERPINF1	8824	5176	Osteogenesis imperfecta, type VI	AR	N/A	N/A	Musculoskeletal	General	Bisphosphonates may reduce fracture frequency, and use of RANKL antibody has been described as potentially beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11771667; 17127117; 21353196; 21826736; 22947550; 23613367
SERPINF2	9075	5345	Alpha-2-plasmin inhibitor deficiency	AD/AR	Pediatric		Hematologic	Hematologic		Anti-fibrinolytic agents or FFP can be used to treat bleeding episodes, and to and prevent patients hemorrhagic complications in those who are undergoing surgical interventions; Intramedullary hematoma is also a common feature, and awareness of this potential manifestation can be beneficial in order to institute efficient treatment; Heterozygotes may also have (milder) manifestations	82839; 156196; 89324; 7095605; 2496145; 2572590; 1806461; 9880645; 10583218; 11472338; 19141165; 19593116; 21873355 
SERPING1	1228	710	Angioedema, hereditary	AD/AR	Pediatric	Allelic with Complement component 4, partial deficiency of (AD)	Allergy/Immunology/Infectious; Gastrointestinal	Allergy/Immunology/Infectious		Medical treatment (eg, with C1 inhibitor concentrate, ecallantide, icatabant) may be beneficial to prevent and/or treat acute attacks	4393526; 4551861; 792688; 7091182; 3587308; 3653633; 3056508; 3693762; 2723063; 2365061; 2296585; 1885769; 1684567; 1339401; 1459574; 8396558; 8330878; 7618673; 7883978; 8755917; 8628358; 11700154; 11743247; 15971231; 16470590; 16813612 ; 17137866; 17502473; 19752569; 20695852; 20818887; 20818888; 20818886; 21208117; 21864911; 22748405; 22800873; 22831796; 22882460; 23123409; 23437219; 23583915; 23607500; 23678554; 23689237
SERPINH1	1546	871	Osteogenesis imperfecta, type X	AR	N/A	N/A	Craniofacial; Dental; Musculoskeletal; Ophthalmologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20188343
SERPINI1	8943	5274	Encephalopathy, familial, with neuroserpin inclusion bodies	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10517635; 12103288
SETBP1	15573	26040	Mental retardation, autosomal dominant 29; Schinzel-Giedion midface retraction syndrome	AD	N/A	N/A	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Renal	General	The condition can involve neoplasms (neuroepithelial neoplasia), as well as multiple congenital malformations affecting a number of organ systems	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	665725; 7506484; 7864048; 8849020; 9738870; 18398855; 20436468; 21371013; 22333924; 23400866; 25217958
SETD5	25566	55209	Mental retardation, autosomal dominant 23	AD	N/A	N/A	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic	General	The condition can involve multiple congenital malformations affecting a number of organ systems	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24680889
SETX	445	23064	Spinocerebellar ataxia, autosomal recessive 1; Amyotrophic lateral sclerosis 4, juvenile; Ataxia with oculomotor apraxia, type 2 	AD/AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7214250; 15106121; 14770181; 15732101; 16717225; 16644229; 17096168; 18405395; 18663494; 19141356; 19569000; 19593598; 19696032; 19727998; 19893583; 21438761; 22088787; 22341623; 22577233; 23111195 
SF3B4	10771	10262	Acrofacial dysostosis 1, Nager type	AD	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22541558; 23568615 
SFTPA2	10799	729238	Idiopathic pulmonary fibrosis and lung cancer	AD	Pediatric		Oncologic; Pulmonary	Oncologic		Surveillance for and early diagnosis of neoplasms could allow potentially be beneficial treatment	19100526
SFTPB	10801	6439	Surfactant metabolism dysfunction, pulmonary 1	AR	Pediatric		Pulmonary	Pulmonary		Lung transplant has been reported as effective in individuals with surfactant B deficiency, and without transplant, the disorder is typically fatal	8421459; 1341413; 8021783; 8071741; 8163685; 7491219; 7647155; 9086529; 9042125; 9506635; 10571948; 10378403; 10365365; 9927351; 11041444; 10960490; 11063734; 10712351; 10663288; 11282516; 11341756; 12784301; 17011330; 17391469; 17109726; 18558554; 19647838; 19220077; 22884059; 23625987
SFTPC	10802	6440	Surfactant metabolism dysfunction, pulmonary, 2	AD	Pediatric		Pulmonary	Pulmonary		There have been reports of individuals who received benefit from medical treatment, including hydroxychloroquine, whole-lung lavage, systemic corticosteroids, azathioprine; Lung transplantation may be indicated in individuals with severe and/or refractory disease	11207353; 11445799; 11893657; 11991887; 15039969; 15293602; 15647591; 19443464
SFXN4	16088	119559	Combined oxidative phosphorylation deficiency 18	AR	N/A	N/A	Biochemical; Hematologic; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24119684
SGCA	10805	6442	Muscular dystrophy, limb-girdle, type 2D	AR	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular		The condition can include severe cardiac manifestations, and knowledge may allow surveillance (eg, with EKG, echocardiogram, and Holter monitoring) and early medical management, which may ameliorate morbidity and mortality; Heart transplantation may be indicated in individuals with severe dilated cardiomyopathy	8069911; 7987694; 8528203; 7663524; 9032047; 18285821; 20627570
SGCB	10806	6443	Muscular dystrophy, limb-girdle, type 2E	AR	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular	Digenic inheritance (with SGCD) has been suggested, but the evidence is unclear	The condition can include severe cardiac manifestations, including lethal ventricular arrhythmias and dilated cardiomyopathy and knowledge may allow surveillance (eg, with EKG, echocardiogram, and Holter monitoring) and early medical management, which may ameliorate morbidity and mortality; Heart transplantation may be indicated in individuals with severe dilated cardiomyopathy	7581448; 8968749; 7581449; 18285821; 20627570 
SGCD	10807	6444	Cardiomyopathy, dilated, 1L; Muscular dystrophy, limb-girdle, type 2F	AR	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular	Digenic inheritance (with SGCB) has been suggested, but the evidence is unclear	The condition can include severe cardiac manifestations, and knowledge may allow surveillance (eg, with EKG, echocardiogram, and Holter monitoring) and early medical management, which may ameliorate morbidity and mortality; Heart transplantation may be indicated in individuals with severe dilated cardiomyopathy	8841194; 8776597; 10735275; 9832045; 10069710; 10974018,; 18285821; 19259135
SGCE	10808	8910	Dystonia, myoclonic	AD	N/A	N/A	Musculoskeletal	General	Treatment with deep-brain stimulation may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4434166; 11528394; 12325078; 12391346; 11912106; 12634861; 12821748; 12743249; 16240355; 15728306; 17101905; 16534121; 16227522; 18362280; 20301587; 20800530; 21220679; 21267590; 22026499 
SGCG	10809	6445	Muscular dystrophy, limb-girdle, type 2C	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1303286; 7481775; 8923014; 8968757; 10507732; 10720277; 16832103; 18285821
SGSH	10818	6448	Mucopolysaccharidosis type IIIA (Sanfilippo syndrome A)	AR	N/A	N/A	Biochemical; Neurologic	General	BMT has been described, but was not reported to have a beneficial effect on prognosis	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4252428; 6796310; 7856659; 7493035; 9158154; 9401012; 9554748; 9727849; 9950362; 10518291; 10727844; 11668611; 12000360; 12702166; 15637719; 21061399
SH2D1A	10820	4068	Lymphoproliferative syndrome, X-linked	XL	Pediatric		Allergy/Immunology/Infectious; Hematologic; Oncologic	Allergy/Immunology/Infectious; Hematologic; Oncologic		Surveillance for EBV infections is indicated; Prompt recognition and treatment of hemophagocytic lymphohistiocytosis (with immunosuppressive agents or rituximab in the case of EBV infection); Treatment for individuals with hypogammaglobulinemia (with IVIG) may be beneficial; Awareness of the increased risk of lymphoma may allow prompt recognition and treatment; HSCT has been described, and is indicated in many individuals 	4852784; 48119; 7188959; 6283885; 1847089; 8559596; 9771704; 11133747; 17620557; 20926771; 21971331 
SH3BP2	10825	6452	Cherubism	AD	N/A	N/A	Craniofacial; Musculoskeletal	General	As bone lesions are typically self-limiting, surgical interventions  treatment may not be necessary (with the exception of aggressive lesions resulting in severe functional issues, or for aesthetic reasons)	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11381256; 17368082; 18596838; 19017279; 20301316; 21045962; 22153076; 22640988; 22640403; 22795151 
SH3PXD2B	29242	285590	Frank-ter Haar syndrome	AR	Pediatric		Cardiovascular; Craniofacial; Neurologic; Ophthalmologic	Cardiovascular; Ophthalmologic; Pharmacogenomic	The condition can include multiple congenital anomalies	The condition may be clinically recognizable, but can include macrocornea with or without glaucoma, and surveillance and prompt treatment may be beneficial; Awareness of cardiac anomalies may allow prompt management; Agents that may contribute to glaucoma should be avoided	4805907; 7158646; 9375925; 9188664; 15523657; 20137777
SH3TC2	29427	79628	Charcot-Marie-Tooth disease, type 4C; Mononeuropathy of the median nerve, mild	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14574644; 16326826; 16924012; 19744956; 20220177; 20301514; 20301641; 21291453; 22950825 
SHANK2	14295	22941	Autism, susceptibility to 17	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20473310
SHANK3	14294	85358	Phelan-McDermid syndrome; Schizophrenia	AD	N/A	N/A	Craniofacial; Neurologic	General	There is evidence that mutations in this gene are also involved in autism-related disorders; Deletions have been described as responsible for features of Chromosome 22q13.3 deletion syndrome	There is evidence that mutations in this gene are also involved in autism-related disorders; Deletions have been described as responsible for feaures of Chromosome 22q13.3 deletion syndrome; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12920066; 17173049; 17999366; 12920066; 20301377; 20385823; 21150887; 21376300; 21606927; 22892527; 22922660
SHH	10848	6469	Holoprosencephaly 3; Microphthalmia with coloboma 5 	AD	N/A	N/A	Craniofacial; Endocrine; Neurologic; Ophthalmologic	General	Mutations in SHH have also been implicated in schizencephaly, but the data are unclear, and this may have co-occurred with typical holoprosencephaly-type malformations; Individuals with holoprosencephaly  may demonstrate endocrine anomalies, including diabetes insipidus	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8896572; 10556296; 11471164; 11479728; 12567406; 12503095; 15221788; 19603532; 20531442; 21940735; 1976454; 20104608; 20301702; 22791840; 23112757 
SHOC2	15454	8036	Noonan-like syndrome with loose anagen hair	AD	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Endocrine; Hematologic; Musculoskeletal; Neurologic	Cardiovascular; Endocrine; Hematologic		Surveillance and treatment related to  manifestations such as cardiac anomalies (which include pulmonic stenosis and hypertrophic cardiomyopathy) can be beneficial; Recognition of endocrine anomalies (eg, GH deficiency) may allow early diagnosis and treatment; Individuals with coagulopathy have been reported, and awareness may allow prompt recognition and management	1884862; 9301585; 12673660; 19684605
SHOX	10853	6473	Langer mesomelic dysplasia; Leri-Weill dyschondrosteosis; Short stature, idiopathic familial	XL/PAR	N/A	N/A	Musculoskeletal	General	GH treatment can be effective in idiopathic short stature; Deletion of regulatory elements can also produce manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14344358; 5410085; 6059604; 7365762; 9140395; 9590292; 9590293; 11030412; 11186941; 10713888; 11403039; 11739418; 11932348; 14557470; 12784295; 15173249; 15173321; 15214013; 16227037; 17935511; 17047016; 17200153; 19578035; 19636220; 20301394; 20412871; 20538086; 20683993; 21712857; 21912078; 22020182; 22071895; 22461651; 22518848; 22572840 
SHROOM4	29215	57477	Stocco dos Santos X-linked mental retardation syndrome	XL	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2063914; 12673656; 16249884
SI	10856	6476	Sucrase-isomaltase deficiency, congenital	AR	Pediatric		Gastrointestinal	Gastrointestinal		Sucrose and other carbohydrate ingestion results in osmotic diarrhea, and dietary/medical therapy (eg, sucrose-reduced diet, treatment with sacrosidase) can be effective	5848222; 6082247; 925457; 3553946; 3807985; 3403721; 1717481; 8648532; 8609217; 8648527; 9932843; 10445568; 10903344; 11340066; 12014995; 14724820; 16329100; 18043509; 19680155; 23103650; 23103652; 23103658
SIGMAR1	8157	10280	Amyotrophic lateral sclerosis 16, juvenile; Frontotemporal lobar degeneration-motor neuron disease	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18755042; 21031579; 21842496 
SIL1	24624	64374	Marinesco-Sjogren syndrome	AR	N/A	N/A	Endocrine; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13053231; 830450; 3683758; 10665502; 14512967; 16282978; 16282977; 17309654; 18285827; 20301371; 20111056; 22219183; 23062754
SIX1	10887	6495	Deafness, autosomal dominant 23; Branchiootorenal syndrome 3; Branchiootic syndrome 3	AD	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Renal	Audiologic/Otolaryngologic; Renal	Individuals can have characteristic aural anomalies, but these may not be readily ascertained	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In BOR, surveillance and treatment/prophylaxis related to vesicoureteral reflux can be beneficial	10777717; 15141091; 16652090; 17637804; 18330911; 20301554 
SIX3	10889	6496	Holoprosencephaly	AD	N/A	N/A	Craniofacial; Endocrine; Neurologic; Ophthalmologic	General	Mutations in SIX3 have also been implicated in schizencephaly, but the data are unclear, and this may have co-occurred with typical holoprosencephaly-type malformations; Individuals with holoprosencephaly  may demonstrate endocrine anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10369266; 15221788; 16199538; 17001667; 19346217; 19353631; 20157829; 20531442; 21940735; 21976454; 23112757 
SIX5	10891	147912	Branchiootorenal syndrome 2	AD	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Renal	Audiologic/Otolaryngologic; Renal	Individuals can have characteristic aural anomalies, but these may not be readily ascertained	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In BOR, surveillance and treatment/prophylaxis related to vesicoureteral reflux can be beneficial	17357085; 20301554 
SIX6	10892	4990	Microphthalmia, isolated, with cataract 2	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15266624
SKI	10896	6497	Shprintzen-Goldberg syndrome	AD	Pediatric		Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	Cardiovascular		Individuals have been described with a number of cardiovascular anomalies, including aortic root dilatation, and spontaneous rupture of arterial aneurysms, and surveillance (eg, including echocardiogram) may allow early management, decreasing morbidity and mortality	23023332
SKIV2L	10898	6499	Trichohepatoenteric syndrome 2	AR	Pediatric		Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal	Allergy/Immunology/Infectious; Gastrointestinal		Antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial; Parenteral nutrition may be required	18982349; 22444670; 23679950
SLC10A2	10906	6555	Bile acid malabsorption, primary	AD	Pediatric		Gastrointestinal	Gastrointestinal		Individuals may present with manifestations of diarrhea/steatorrhea such as anasarca and nutritional deficiencies due to fecal loss, and dietary and medical interventions (eg, medium chain triglycerides, bile acid sequestrants) may be beneficial	1017717; 430290; 7106511; 9109432; 9109422; 19823678; 21649730 
SLC11A2	10908	4891	Anemia, hypochromic microcytic, with iron overload	AR	Pediatric		Hematologic	Hematologic		Individuals can require RBC transfusions and erythropoietin treatment; As hepatic iron overload is common, awareness may allow monitoring and adjustment of treatments and surveillance accordingly	14135503; 15459009; 16439678; 16160008; 16584902; 21871825; 22313374 
SLC12A1	10910	6557	Bartter syndrome, antenatal, type 1	AR	Pediatric		Renal	Renal		Sequelae can be lethal; Medical treatment of manifestations including hypokalemia and metabolic alkalosis (eg, with KCl supplementation, NSAIDs), as well as related findings such as nephrocalcinosis, can be beneficial	3863906; 8457138; 3888887; 8640224; 9355073; 19513753; 20219833 
SLC12A3	10912	6559	Gitelman syndrome	AR	Pediatric		Cardiovascular; Renal	Cardiovascular; Renal	Individuals have been reported with cardiovascular manifestations	Surveillance for, treatment of, and prevention of electrolyte abnormalities may be beneficial; Individuals with cardiovascular manifestations (eg, arrhythmias such as QTc prolongation) that may warrant interventions have also been described	5929460; 1436349; 81436349; 16120871; 17000984; 17981812; 22009145 
SLC12A6	10914	9990	Agenesis of the corpus callosum with peripheral neuropathy (Andermann syndrome)	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14397896; 6329500; 12368912; 12838516; 16606917; 17893295; 20020398; 20301546 
SLC13A5	23089	284111	Epileptic encephalopathy, early infantile 25	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24995870
SLC14A1	10918	6563	Blood group, Kidd	BG	Pediatric	 	Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion); Jk deficiency may be associated with a urine concentration defect	1498276; 9215669; 11807016
SLC16A1	10922	6566	Hyperinsulinemic hypoglycemia, familial, 7; Erythrocyte lactate transporter defect; Monocarboxylate transporter 1 deficiency (AR)	AD/AR	Pediatric (Erythrocyte lactate transporter defect; Monocarboxylate transporter 1 deficiency ); Adult (Hyperinsulinemic hypoglycemia, familial, 7)		Biochemical; Endocrine; Musculoskeletal; Neurologic; Renal	Biochemical; Endocrine; Musculoskeletal; Renal	Depending on the allelic condition, manifestations in dominant conditions may involve primarily endocrine or musculoskeletal/renal manifestations	In Hyperinsulinemic hypoglycemia, familial, several affected individuals have reported as manifesting with severe sequelae, such as hypoglycemia-induced seizures, which could potentially be averted by early recognition and treatment; In Erythrocyte lactate transporter defect, exercise and heat exposure may result in sequelae such as rhabdomyolysis, and precautions may be beneficial; In Monocarboxylate transporter 1 deficiency, ensuring adequate caloric intake has been reported as beneficial to decrease the frequency of episodes of ketoacidotic episodes, and medical management (eg, with intravenous glucose or dextrose and bicarbonate) of episodes has been described as effective in terms of immediate management, and related long-term sequelae	3775384; 3395513; 3395514; 1358043; 10590411; 11207177; 12502513; 17701893; 25390740
SLC16A12	23094	387700	Cataract, juvenile, with microcornea and glucosuria	AD	N/A	N/A	Biochemical; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17458810; 18304496
SLC16A2	10923	6567	Allan-Herndon-Dudley syndrome	XL	Pediatric		Craniofacial; Endocrine; Musculoskeletal; Neurologic	Endocrine; Obstetric		In mutation positive males, treatment with thyroid hormone has not been described as affecting the neurologic phenotype, but heterozygous women may benefit from monitoring and levothyroxine treatment during pregnancy in order to prevent fetal/neonatal hypothyroidism (regardless of fetal mutation status)	8484404; 15488219; 14661163; 15889350; 15980113; 18398436; 19194886; 20301789; 20713192; 21098685; 21415082; 21468521 
SLC17A5	10933	26503	Infantile sialic acid storage disorder; Sialuria, Finnish type (Salla disease)	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4043964; 10546100; 10069709; 10581036; 10947946; 12121352; 12794687; 12794688; 15172005; 16170568; 19557856; 20101035; 20301643; 20637281 
SLC17A8	20151	246213	Deafness, autosomal dominant 25	AD	N/A	N/A	Audiologic/Otolaryngologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11115382; 18674745
SLC17A9	16192	63910	Porokeratosis, disseminated superficial actinic, 8	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	25180256
SLC19A2	10938	10560	Thiamine-responsive megaloblastic anemia syndrome	AR	Pediatric		Audiologic/Otolaryngologic; Endocrine; Hematologic	Endocrine; Hematologic		High-dose thiamine can improve anemia and may ameliorate diabetes; Individuals may also have sensorineural hearing loss, but prelingual onset appears to have not been reported	5767338; 671156; 6175336; 2540004; 1326679; 7707690; 10391221; 10391223; 10074490; 10978358; 19643445; 20301459; 22369132; 22576805; 22876572 
SLC19A3	16266	80704	Thiamine metabolism dysfunction syndrome 2 (biotin or thiamine responsive)	AR	Pediatric		Biochemical; Neurologic	Biochemical		Medical management (with biotin and/or thiamine) has been reported as beneficial; During crises, medical management with biotin and/or thiamine has been reported as resulting in marked improvement within days, and untreated encephalopathies can result in permanent dystonia	9679779; 15871139; 19387023; 20065143; 21176162; 22777947; 23423671; 24878501
SLC1A1	10939	6505	Schizophrenia	AD	N/A	N/A	Neurologic	General	A single family with a deletion involving the gene has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23341099
SLC1A3	10941	6507	Episodic ataxia, type 6	AD	Pediatric		Neurologic	Neurologic		Invididuals present with attacks of episodic ataxia, which may be severe in some individuals, and treatment with acetazolamide has been reported as being effective	16116111; 19139306
SLC20A2	10947	6575	Basal ganglia calcification, idiopathic, 3	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20552677; 22327515
SLC22A12	17989	116085	Hypouricemia, renal 1	AR	Pediatric		Renal	 Renal		The condition may be asymptomatic, but a minority of individuals can be affected by nephrolithiasis and/or exercise-induce acute renal failure, and preventive measures can be beneficial	12024214; 14655203; 18492088
SLC22A5	10969	6584	Carnitine deficiency, systemic primary	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	Biochemical; Pharmacogenomic		Early disease recognition with prompt carnitine therapy can be immediately life-saving and beneficial long-term; Certain agents (eg, specific antibiotics) have been reported to precipitate severe reactions, and should be avoided	234182; 7432384; 7254270; 7131143; 3974805; 3181209; 31856352235122; 1763895; 2235122; 9826541; 9700603; 11261427; 9634512; 9916797; 11715001; 12210323; 15303004; 16652335; 17126586; 20027113; 20574985; 21922592; 22566287; 22989098; 23379544
SLC24A1	10975	9187	Night blindness, congenital stationary, type 1D	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20850105
SLC24A4	10978	123041	Ameliogenesis imperfecta, hypomaturation type, IIA5	AR	N/A	N/A	Dental 	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23375655; 24621671
SLC25A1	10979	6576	Combined D-2- and L-2-hydroxyglutaric aciduria	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10963100; 23393310; 23561848
SLC25A12	10982	8604	Hypomyelination, global cerebral	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19641205
SLC25A13	10983	10165	Citrin deficiency	AR	Pediatric		Biochemical; Gastrointestinal; Hematologic; Neurologic; Oncologic	Biochemical; Oncologic	The adult-onset form may present after the pediatric interval	Dietary (galactose-free diet) and pharmacotherapy (eg, sodium benzoate, sodium phenylbutyrate, and arginine) can be beneficial; Individuals may be at increased risk of hepatocellular carcinoma, and awareness may allow preventive measures, early detection, and treatment; Liver transplantation can be effective	10369257; 11153906; 11281457; 11343052; 11343053; 17323144; 18367750; 12111366; 20301360; 21161389; 21424115; 21914561; 22710133; 22277121; 22892490; 23053473; 23067347; 23112554
SLC25A15	10985	10166	Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome	AR	Pediatric		Biochemical; Gastrointestinal; Neurologic	Biochemical		Dietary (eg, low protein diet,) and medical therapy (eg, with ornithine, citrulline and phenylbutyrate sodium), including during pregnancy, has been reported as beneficial	5782534; 3091924; 3116497; 3670619; 3106719; 3407856; 2222247; 10369256; 11355015; 11552031; 16940241; 18978333; 19242930; 20574716; 22465082 
SLC25A19	14409	60386	Thiamine metabolism dysfunction syndrome 4; Microcephaly, Amish type	AR	N/A	N/A	Biochemical; Neurologic	General	High fat diet has been reported as being beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12185364; 19798730; 20583149
SLC25A20	1421	788	Carnitine-acylcarnitine translocase deficiency	AR	Pediatric		Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic 	Biochemical; Cardiovascular		Early recognition and dietary/medical treatment in both the immediate and long-term setting (eg, with IV glucose, dialysis, high-carbohydrate/low-fat diet with frequent feeds and medium-chain triglycerdies, and carnitine) can be beneficial; Awareness of potential cardiovascular sequelae can allow prompt recognition and management	1598097; 7807931; 7564255; 8739960; 9399886; 9323572; 9686371; 9544911; 10384385; 15057979; 15365988; 15363639; 16919490; 17277394; 17508264; 21605995; 24088670
SLC25A22	19954	79751	Epileptic encephalopathy, early infantile, 3	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15592994; 19780765; 24596948
SLC25A3	10989	5250	Micochondrial phosphate carrier deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17273968
SLC25A38	26054	54977	Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive	AR	Pediatric		Hematologic	Hematologic		Individuals may have chronic, transfusion-dependent anemia refractory to pyridoxine, and diagnosis may allow early transfusion-based treatment	19412178; 21393332 
SLC25A4	10990	291	Progressive external ophthalmoplegia with mitochondrial DNA deletions 3; Cardiomyopathy, familial hypertrophic	AD/AR	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Musculoskeletal; Neurologic	Cardiovascular	Cardiomyopathy has only been described in an individual with a homozygous mutation	In PEO, individuals have been described with endocrinopathy (eg, thyroid dysfunctiona), and awareness may allow prompt detection and treatment; In Cardiomyopathy, familial hypertrophic, surveillance (eg, with echocardiography/electrocardiography), preventive measures and medical management related to cardiomyopathy may decrease morbidity and mortality	10926541; 11756592; 1756613; 12112115; 12210792; 16155110
SLC26A2	10994	1836	Achondrogenesis, type IB; Atelosteogenesis II; De la Chapelle dysplasia; Diastrophic dysplasia; Epiphyseal dysplasia, multiple, 4	AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13993535; 5703690; 3799721; 4644462; 4064368; 3562108; 8528239; 8571951; 8723083; 8931695; 8723100; 1345170; 7923357; 9108864; 10482955; 10466420; 10465113; 11734236; 11565064; 11303514; 12525546; 12966518; 12220459; 15316973; 18708426; 18925670; 20301483; 20301689; 20525296; 21077202; 21155763; 21922596; 22052783 
SLC26A3	3018	1811	Diarrhea 1, secretory chloride, congenital	AR	Pediatric		Gastrointestinal	Gastrointestinal		Due to copious high-chloride diarrhea individuals may manifest with with dehydration and electrolyte imbalances such as hypokalemia, and metabolic alkalosis, and recognition can allow monitoring of electrolyte and hydration status and appropriate supportive therapy with oral intake of chloride, sodium, and potassium to ensure an appropriate electrolyte balance, as well as medications such as omeprazole to reduce fecal electrolyte output	4162682; 324405; 2651131; 8988888; 11524734; 12442266; 16641574; 17120762; 19861545; 19912155; 19967661; 21332001; 21394828; 21694535; 22277064; 22779076; 23274434
SLC26A4	8818	5172	Pendred syndrome; Deafness, autosomal recessive 4; Enlarged vestibular aqueduct, digenic 	AR	Pediatric		Audiologic/Otolaryngologic; Endocrine 	Audiologic/Otolaryngologic; Endocrine	Promoter variants have been reported as causative; Digenic inheritance (with KCNJ10) has been reported	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Pendred syndrome, surveillance for and treatment of thyroid abnormalities can be beneficial	9398842; 9500541; 9920104; 10190331; 10902795; 11317356; 14508505; 15689455; 16570074; 17690912; 17503324; 19426954; 21488278; 20301640 
SLC26A5	9359	375611	Deafness, autosomal recessive 61	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic	Heterozygosity has been observed in individuals with hearing loss as well, indicating possible semidominance	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	12719379
SLC26A8	14468	116369	Spermatogenic failure 3	AD	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23582645
SLC27A4	10998	10999	Ichthyosis prematurity syndrome	AR	N/A	N/A	Dermatologic; Obstetric	General	The obstetric manifestations involve maternal mid-trimester complications of pregnancy leading to prematurity	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19631310; 21856041; 22927265
SLC29A3	23096	55315	Histiocytosis-lymphadenopathy plus syndrome 	AR	Pediatric	Allelic with Dysosteosclerosis (AR)	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Endocrine; Gastrointestinal; Musculoskeletal	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dermatologic; Endocrine		Lipogranulomatous infiltration has been reported as benefiting from surgical interventions, radiotherapy, and medical treatment (eg, with cylophosphamide, prednisolone); Hormonal insufficiency, including hypogonadotropic hypogonadism, hypothyroidism, and growth hormone deficiency, may benefit from medical treatment; Individuals may manifest with early-onset hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	16118898; 16631937; 16650224; 16155931; 16155931; 18940313; 19336477; 19175903; 19889517; 20140240; 20199414; 20199539; 20399510; 20619369; 21178579; 21888995; 22238637; 22356918; 22653152; 22875837; 22989030; 23058913; 23406517; 23530176; 23623699
SLC2A1	11005	6513	GLUT1 deficiency syndrome 1; GLUT1 deficiency syndrome 2	AD/AR	Pediatric		Hematologic; Neurologic	Hematologic; Neurologic		Correct diagnosis is important, as ketogenic diet may result in marked clinical improvement of seizures and motor symptoms; Individuals have been described with anemia requiring transfusions	9462754; 10980529; 11603379; 12555938; 12548383; 15132717; 16171377; 15622525; 18451999; 18577546; 19304421; 19630075; 19901175; 20574033
SLC2A10	13444	81031	Arterial tortuosity syndrome	AR	Pediatric		Cardiovascular; Dermatologic; Genitourinary; Musculoskeletal; Renal	Cardiovascular		Individuals appear to be at increased risk of cradiovascular manifestations, such as ischemic events, arterial aneurysm, and other findings, and preventive measures and prompt treatment may be beneficial	6033167; 12801113; 16550171; 17935213; 18565096; 19508422; 19781076 
SLC2A2	11006	6514	Fanconi-Bickel syndrome; Glycogen storage disease XI; Neonatal diabetes mellitus	AR	Pediatric		Biochemical; Endocrine; Gastrointestinal; Renal	Biochemical; Endocrine		Dietary measures (eg, frequent feeds, cornstarch) can be beneficial; In mildly affected individuals, dietary measures (eg,  free glucose and galactose restriction) may be beneficial in terms of growth; Individuals may also manifest with neonatal diabetes mellitus, and awareness may allow preventive measures and prompt treatment related to severe episodes	15397919; 6274135; 3153325; 8362811; 7632512; 7564233; 9266402; 9354798; 10987651; 11044475; 11810292; 19480329; 21271664; 22145468; 22350464; 22214819; 22060631; 22831748; 22660720 
SLC2A9	13446	56606	Hypouricemia, renal, 2	AD/AR	Pediatric		Renal	Renal	The youngest reported individual was an adult, but morbidity could theoretically appear earlier	The condition may be associated with complications including exercise-induced acute renal failure and nephrolithiasis, and preventive measures (eg, related to exercise) may be beneficial	9026395; 19926891; 22132964; 21536615 
SLC30A10	25355	55532	Hypermanganesemia with dystonia, polycythemia, and cirrhosis	AR	Pediatric		Biochemical; Gastrointestinal; Hematologic; Neurologic	Hematologic		The condition can involve hypermagnesemia, with gastrointestinal, neurologic, and other sequelae, and chelation therapy has been described as beneficial in some individuals	11040156; 18087599; 18392750; 21596707; 22341971; 22341972
SLC33A1	95	9197	Congenital cataracts, hearing loss, and neurodegeneration	AR	Pediatric	Allelic with Spastic paraplegia 42, autosomal dominant (AD)	Audiologic/Otolaryngologic; Biochemical; Neurologic; Ophthalmologic	Audiologic/Otolaryngologic; Biochemical		Medical treatment (with copper supplementation) has been reported as biochemically and clinically beneficial in some individuals; Awareness of the potential of hearing loss may allow early identification and interventions to support speech and language development	15902551; 19061983; 20461110; 22243965; 22508683
SLC34A1	11019	6569	Fanconi renotubular syndrome 2; Nephrolithiasis/osteoporosis, hypophosphatemic, 1 	AR	Pediatric		Renal	Renal		In Fanconi renotubular syndrome 4, treatment with neutral phosphate has been reported as resulting in improvement in some but not all clinical, radiological, and laboratory parameters; Due to increased renal phosphate loss, individuals may be at increased risk of renal stone formation and/or bone demineralization	2842681; 12324554; 0335586
SLC34A2	11020	10568	Pulmonary alveolar microlithiasis	AR	Pediatric		Pulmonary	Pulmonary	Individuals with cardiovascular valvular anomalies have been described	Treatment with disodium editronate has been reported as effective	1485012; 9097354; 9258573; 11287838; 12210357; 12357485; 11956731; 12700375; 16960801; 20425862; 22336687 
SLC34A3	20305	142680	Hypophosphatemic rickets with hypercalciuria, hereditary	AR	Pediatric		Renal	Renal	Heterozygotes may show mild manifestations	The condition can result in sequelae such as severe rickets, and supplementation (eg, with phosphate) can be effective to treat many sequelae	2983203; 3796683; 1436310; 16358214; 16358215
SLC35A1	11021	10559	Congenital disorder of glycosylation, type IIf	AR	Pediatric		Allergy/Immunology/Infectious; Hematologic; Neurologic	Allergy/Immunology/Infectious; Hematologic	Hepatic-metabolized medications should be avoided	The condition can include infectious risks (as well as other hematologic anomalies), and antiinnfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been described;  Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	11157507; 15576474
SLC35A2	11022	7355	Congenital disorder of glycosylation, type Iim	XL	Pediatric		Allergy/Immunology/Infectious; Craniofacial; Hematologic; Neurologic	Allergy/Immunology/Infectious; Hematologic	Hepatic-metabolized medications should be avoided	The condition can include infectious risks (as well as other hematologic anomalies), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	23561849; 24115232
SLC35A3	11023	23443	Arthrogryposis, mental retardation, and seizures	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24031089
SLC35C1	20197	55343	Congenital disorder of glycosylation, type IIc; Leukocyte adhesion deficiency, type II	AR	Pediatric		Allergy/Immunology/Infectious; Biochemical; Neurologic	Allergy/Immunology/Infectious; Biochemical; Hematologic	Hepatic-metabolized agents should be avoided	Treatment with fucose has been described as effective in some individuals; Surveillance for and prompt treatment of infections may be beneficial;  Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	1279426; 10590041; 11213799; 11326280; 11133780; 12116250; 21175687; 20301507
SLC35D1	20800	23169	Schneckenbecken dysplasia	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11200994; 17952091; 19508970
SLC36A2	18762	153201	Hyperglycinuria; Iminoglycinuria; Iminoglycinuria, digenic	AD/AR/Digenic	N/A	N/A	Biochemical; Renal	General	Variants in other genes (eg, SLC6A18, SLC6A19, SLC6A20) may affect manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19033659
SLC37A4	4061	2542	Glycogen storage disease Ib; Glycogen storage disease Ic; Glycogen storage disease Id	AR	Pediatric		Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Oncologic; Renal	Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Oncologic; Renal		Dietary measures can be beneficial allow optimal glucose levels and promote growth and development (additionally, specific carbohydrate sources should be limited); Allopurinol to prevent gout and lipid-lowering medications to prevent hyperlipidemia may be necessary when dietary therapy is ineffective; Citrate supplementation and ACE inhibitors may help prevent development of decrease renal complications, though renal transplant may ultimately be necessary; Surveillance for and treatment of hepatic neoplasms (including liver transplant in some) can be beneficial;  G-CSF may be beneficial due to recurrent infections	4300573; 212064; 6928812; 6578929;  6298622; 6309784; 3860000; 3459848; 3464427; 2311631; 1719175; 1375344; 8319729; 273986; 8758135; 9428641; 9758626; 9686363; 10931421; 12576310; 20301489; 21575371; 21599942;  21629566
SLC38A8	32434	146167	Foveal hypoplasia 2	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24045842; 24290379
SLC39A13	20859	91252	Spondylocheirodysplasia, Ehlers-Danlos syndrome-like	AR	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18985159; 18513683
SLC39A4	17129	55630	Acrodermatitis enteropathica	AR	Pediatric		Biochemical; Dermatologic; Gastrointestinal	Biochemical	Heterozygous mutations have been reported as disease-associated in some reports	The condition may present with failure to thrive, diarrhea, and dermatitis, and, if untreated, may evolve to include other sequelae of zinc deficiency, including immunodeficiency and neurologic manifestations, and medical management (eg, treatment with oral zinc therapy) can be effective	4136854; 1090826; 12068297; 19370757; 20883266; 21165302; 21762381; 21906148; 21907902; 22082465; 22166942; 23228939; 23430849
SLC39A5	20502	283375	Myopia 24	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24891338
SLC3A1	11025	6519	Cystinuria	AR	Pediatric		Biochemical; Renal	Biochemical; Renal		Measures to maintain high fluid intake, as well as medical therapy (eg, urine alkalinization, and, in some, penicillamine) can be beneficial	5925065; 2502678; 8054986; 7573036; 12239244; 12820697; 15635077; 19782624; 20052367; 20399395; 21255007; 21677404; 21863055
SLC40A1	10909	30061	Hemochromatosis, type 4	AD	Pediatric		Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic	Biochemical; Gastrointestinal; Hematologic	Biallelic mutations (with other hemochromatosis-related genes, such as HFE) have been reported	Phlebotomy may be beneficial in some individuals, but genetic diagnosis may be useful to direct treatment regimens, as some indviduals may have reduced tolerance to phlebotomy and can become anemic on therapy despite persistently elevated serum ferritin 	1518736; 11431687; 14752817; 14757427; 15030991; 16351644; 15831700; 17566043; 17383046; 19709084; 19342478; 19589941; 20230395; 21175851; 21411349; 22584997; 22890139
SLC41A1	19429	254428	Nephronophthisis-like ciliopathy	AR	Pediatric		Allergy/Immunology/Infectious; Renal	Allergy/Immunology/Infectious	Renal transplantation has been described	Individuals have been described with frequent  respiratory infections (including with Pseudomonas aeruginosa in one reported individual), and awareness of infectious risk may allow preventive management as well as prompt and aggressive treatment	23661805
SLC45A2	16472	51151	Oculocutaneous albinism, type IV; Skin/hair/eye pigmentation 5	AD/AR	N/A	N/A	Dermatologic; Ophthalmologic	General	In Oculocutaneous albinism, type IV, Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Variants associated with Skin/hair/eye pigmentation 5 are associated with a slight increased risk of skin cancer, but clinical applicability is otherwise unclear	11574907; 14722913; 14961451; 15714523; 17358008; 17999355; 19578363
SLC46A1	30521	113235	Folate malabsorption, hereditary	AR	Pediatric		Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Hematologic; Neurologic	Biochemical		Individuals may present in infancy with anemia, diarrhea, infections/immune deficiency, and cognitiive impairment, and treatment (eg, with folate/folinic acid supplementation) can be effective	5450108; 3987728; 2381546;  11804211; 11807405; 7129779; 17641272; 18559978; 17446347; 21333572; 21489556
SLC4A1	11027	6521	Spherocytosis, type 4; Ovalcytosis; Renal tubular acidosis, distal, with hemolytic anemia; Renal tubular acidosis, distal, autosomal dominant; Renal tubular acidosis, distal, autosomal recessive; Blood group, Wright; Blood group, Waldner; Blood group, Diego; Blood group, Froese; Blood group, Swann	AD/AR/BG	Pediatric	Allelic with Acanthocytosis, Band 3 Memphis (AR)	Hematologic; Renal	Hematologic; Renal		In Renal tubular acidosis, if detected early, therapeutic correction of the acidosis by alkali administration leads in most cases to improvement of biochemical abnormalities and resumption of normal growth, as well as beneficial regarding skeletal manifestations; As pertains to hematologic manifestations, splenectomy has been reported as being effective; Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	13288586; 13669428; 13739450; 6025225; 2829189; 2146504; 1824272; 1536803; 1519367; 1737855; 1520883; 8343110; 7713501; 8206915; 8282779; 7919393; 7812009; 8547122; 8704215; 8608262; 8567957; 9207478; 9312167; 9734643; 9973643; 9600966; 9854053; 10403343; 10926824; 11061863; 10942416; 11155072; 11380459; 11756190; 12087557; 15211439; 16227998; 19229254; 19297287; 20799361;  20825599; 20960171; 22126643; 22609520; 22693689; 22919024; 23255290; 23498825; 23878048; 24257694
SLC4A11	16438	83959	Corneal dystrophy, Fuchs endothelial 4; Corneal endothelial dystrophy 2, autosomal recessive; Corneal endothelial dystrophy and perceptive deafness 	AD/AR	N/A	N/A	Audiologic/Otolaryngologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16767101; 17220209; 18024964; 20848555; 21203343; 22072594 
SLC4A4	11030	8671	Renal tubular acidosis, proximal, with ocular abnormalities and/or migraine	AD/AR	Pediatric		Dental; Neurologic; Ophthalmologic; Renal	Ophthalmologic; Renal	Heterozygous mutations may result in ophthalmologic anomalies (including glaucoma) and migraine susceptibility	Medical treatment of renal tubular acidosis may be beneficial; Diagnosis may allow early treatment related to ocular anomalies, which can include glaucoma	8142230; 10545938; 11274232; 20798035 
SLC52A1	30225	55065	Maternal riboflavin deficiency	AD	Pediatric		Biochemical; Neurologic	Biochemical	Theoretically, biallelic mutations could contribute to disease similar to that arising from mutations in SLC52A2 or SLC52A3	One individual with a heterozygous deletion has been reported, and this was postulated as contributing to transient neonatal-onset glutaric aciduria Type 2 in this individual's offspring,which was reported as being effectively treated by riboflavin therapy	17689999; 21089064; 23107375
SLC52A2	30224	79581	Brown-Vialetto-Van Laere syndrome 2	AR	Pediatric		Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	Audiologic/Otolaryngologic; Biochemical		Individuals may manifest with progressive neurological dysfunction, and there is evidence that medical/dietary management (with high-dose riboflavin therapy) may be beneficial; Awareness of the potential for hearing loss may allow early interventions related to speech and language development	22740598; 23107375; 23243084 
SLC52A3	16187	113278	Brown-Vialetto-Van Laere syndrome 1; Fazio-Londe disease	AR	Pediatric		Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	Biochemical		Individuals typically manifest with progressive neurological dysfunction, including hearing loss, and there is evidence that high-dose riboflavin therapy may be beneficial in some individuals	13900073; 5969547; 5563586; 7425580; 7229669; 2325091; 16122634; 20206331; 20920669; 21110228; 22098162; 22740598; 22633641; 22211384; 23107375 
SLC5A1	11036	6523	Glucose/galactose malabsorption	AR	Pediatric		Gastrointestinal	Gastrointestinal		Individuals typically present in infancy with severe osmotic diarrhea and consequent dehydration, which can be fatal without dietary elimination of glucose and galactose (ie, individuals demonstrate dramatic improvement  on fructose-based formula)	11406349; 2008213; 8985845; 8844006; 9815014; 12139397; 17169300; 18288487; 20486940; 22843301; 23107089; 24048166
SLC5A2	11037	6524	Renal glucosuria	AD/AR	N/A	N/A	Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12436245; 21165652
SLC5A5	11040	6528	Thyroid dyshormonogenesis 1	AR	Pediatric		Endocrine; Oncologic	Endocrine; Oncologic	Neoplasms have been reported as well as endocrine manifestations	Medical  treatment of hypothyroidism (eg, with T4) can be effective; Thyroid neoplasms have also been reported, and surveillance may be beneficial	9171822; 19916865; 21543982; 21565787
SLC6A19	27960	340024	Hartnup disease	AR	Pediatric	Variants may be involved in Iminoglycinuria, digenic (digenic)	Biochemical; Dermatologic; Neurologic; Renal	Biochemical; Dermatologic		Medical therapy (nicotinamide) and sun avoidance can be beneficial for pellagra-like findings; Optimal protein-related treatment is unclear	13358233; 5647741; 5813128; 5041315; 2582682; 11394870; 15286787; 15286788; 19033659; 19185582; 19335424; 20399395 
SLC6A2	11048	6530	Orthostatic intolerance	AD	N/A	N/A	Endocrine; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10684912; 11458707; 12805287
SLC6A20	30927	54716	Iminoglycinuria, digenic; Hyperglycinuria/Iminoglycinuria, modifier of	AD/Digenic	N/A	N/A	Biochemical; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19033659
SLC6A3	11049	6531	Parkinsonism-dystonia, infantile	AR	N/A	N/A	Neurologic	General	Described patients demonstrated poor clinical responses to multiple therapeutic agents	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19478460; 22279524
SLC6A5	11051	9152	Hyperekplexia 3	AR	Pediatric		Neurologic	Neurologic		Neonates are at risk of sudden death from apnea/aspiration, and surveillance, as well as primary prevention with medical treatments (eg, clonazepam) may be beneficial	1334371; 1355335; 16751771; 22753417; 22700964; 20301437 
SLC6A8	11055	6535	Creatine deficiency syndrome 1	XL	Pediatric		Audiologic/Otolaryngologic; Biochemical; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic	Biochemical 		Medical treatment (with  oral creatine, arginine, and/or glycine supplementation) has been described as beneficial in some patients, as measured by increased  cerebral creatine or improved clinical findings	11261517; 11326334; 11898126; 12210795; 12889669; 15154114; 16738945; 17101918; 18569740; 19188083; 20301745; 20501887; 20528887; 20717164; 20846889; 21144783; 21556832; 21660517; 22644605; 22281021; 23660394; 23644449; 24953403
SLC7A14	29326	57709	Retinitis pigmentosa 68	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24670872
SLC7A7	11065	9056	Lysinuric protein intolerance	AR	Pediatric		Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Pulmonary; Renal	Biochemical		Individuals may manifest with a range of  manifestations (eg, developmental delay, failure to thrive with malabsorption, anemia/thrombocytopenia, immunodeficiency, osteoporosis, hemophagocytic lymphohistiocytosis, and pulmonary and renal complications), and dietary/medical therapy (eg, protein restriction, citrulline substitution with use of nitrogen scavengers, lysine supplementation, and carnitine supplementation when necessary) may be beneficial	4158034; 6076999; 5666624; 5431208; 5553484; 7204568; 3917550; 2732736; 8163273; 8655715; 8892019; 10080183; 9931537; 10080182; 10655553; 10737982; 10451527; 17764084; 18328359; 18716612; 20301535; 21308987; 21716135; 22402328; 22876067; 23358709; 23430827; 23542076; 23772603
SLC7A9	11067	11136	Cystinuria	AR	Pediatric		Biochemical; Renal	Biochemical; Renal		Measures to maintain high fluid intake, as well as medical therapy (eg, urine alkalinization, and, in some, penicillamine) can be beneficial	5925065; 2502678; 10471498; 11157794; 12239244; 12371955; 12820697; 12820697; 17539912
SLC9A3R1	11075	9368	Nephrolithiasis/osteoporosis, hypophosphatemic, 2	AD	Adult		Renal	Renal		Due to increased renal phosphate loss, individuals may be at increased risk of renal stone formation and/or bone demineralization, and preventive measures may be beneficial	18784102
SLC9A6	11079	10479	Mental retardation, X-linked syndromic, Christianson type	XL	N/A	N/A	Craniofacial; Neurologic	General	In addition to other features, retinitis pigmentosa has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10528855; 18342287; 19377476; 20949524; 22931061
SLC9A9	20653	285195	Autism susceptibility 16	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18621663
SLCO1B1	10959	10599	Statin-induced myopathy; Hyperbilirubinemia, Rotor type, digenic	AD/Digenic	N/A	N/A	Gastrointestinal	General; Pharmacogenomic	For Statin-induced myopathy, the presence of variants may indicate an increased risk of adverse events (eg, with statins), or may additionally be associated with indications for dosing/medication selection (eg, with rifampin) For Hyperbilirubinemia, Rotor type, digenic, inheritance involves SLCO1B1 and SLCO1B3	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	766621; 18781850; 18823304; 18854776; 19238654; 18650507; 19901119; 21178985; 21142914; 19952871; 21243006; 21709081; 21386754; 22462750; 22232210; 22668755; 22749334; 22850760 
SLCO1B3	10961	28234	Hyperbilirubinemia, Rotor type, digenic	Digenic	N/A	N/A	Gastrointestinal	General	Inheritance involves SLCO1B1 and SLCO1B3	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	766621; 22232210
SLCO2A1	10955	6578	Hypertrophic osteoarthropathy, primary, autosomal recessive 2; Primary hypertrophic osteoarthropathy	AD/AR	N/A	N/A	Dermatologic; Musculoskeletal	General	Heterozygotes may show mild manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16283874; 20889364; 22553128; 22331663; 22197487
SLITRK1	20297	114798	Trichotillomania; Tourette syndrome	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16224024; 17083340; 18021920; 17712845
SLURP1	18746	57152	Mal de Meleda	AD/AR	N/A	N/A	Dermatologic	General	Heterozygotes may display milder manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4281438; 9887370; 11285253; 14756676; 20854438; 21690549; 23290002
SLX4	23845	84464	Fanconi anemia type P	AR	Pediatric		Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Hematologic; Oncologic	Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended	21240275; 21240277; 20301575
SMAD3	6769	4088	Aneurysms-osteoarthritis syndrome; Loeys-Dietz syndrome, type 3	AD	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal	Cardiovascular		Preventive measures and medical management may be helpful to help decrease morbidity, especially related to cardiovascular complications, which can result in sequelae such as sudden death, primarily due to aortic dissection and/or rupture	21217753; 21778426; 22167769 
SMAD4	6770	4089	Hereditary hemorrhagic telangiectasia, type 1; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome; Polyposis, juvenile intestinal; Myhre syndrome	AD	Pediatric		Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Hematologic; Oncologic	Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Hematologic; Oncologic		Individuals with HHT and JPS/HHT may have a variety of vascular complications, including arteriovenous malformations, aortic dilatation, and bleeding diatheses, and surveillance and early intervention related to manifestations (eg, related to thromboembolism or hepatic disease) may decrease morbidity and mortality; In JPS and JPS/HHT, surveillance and early diagnosis/treatment of malignancy (eg, colon cancer) may be beneficial; In Myhre syndrome, individuals may manifest with multisystemic features, including hearing impairment (for which appropriate interventions may be beneficial related to speech and language development) as well as cardiovascular anomalies, and appropriate surveillance may allow prompt diagnosis and treatment	7372073; 7296942; 9582123; 11568925; 12136244; 15031030; 15235019; 16152648; 15723310; 15754356; 16613914; 16690726; 17873119; 18824676; 20101697; 21465659; 21490502; 22158539; 22810475; 21835029; 22243968; 20301525 
SMAD6	6772	4091	Aortic valve disease 2	AD	Pediatric		Cardiovascular	Cardiovascular		Individuals may manifest with sequelae of cardiovascular anomalies including bicuspid, aortic valve, aortic stenosis, and aortic coarctation, and awareness may allow early detection and medical/surgical management, which may ameliorate morbidity and mortality	22275001
SMAD9	6774	4093	Pulmonary hypertension, primary 2	AD	Pediatric		Cardiovascular; Pulmonary	Cardiovascular; Pulmonary		While prognosis is overall poor, medical therapy (eg, with, oral calcium antagonists, anticoagulants, epoprostenol) may be beneficial, though heart/lung transplantation may be required; Control of complications may be beneficial	19211612
SMARCA2	11098	6595	Nicolaides-Baraitser syndrome	AD	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19606471; 22366787; 22822383 
SMARCA4	11100	6597	Rhabdoid tumor predisposition syndrome 2	AD	Pediatric	Allelic with Mental retardation, autosomal dominant 16 (AD); Coffin-Siris syndrome (AD)	Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Genitourinary	Oncologic	Coffin-Siris syndrome can involve multiple congenital anomalies	Individuals may be at high risk for a variety of undifferentiated tumor types, and surveillance and early diagnosis/treatment may be beneficial	20137775; 22426308; 23775540; 24658001; 24658002; 24752781
SMARCAD1	18398	56916	Adermatoglyphia	AD	N/A	N/A	Dermatologic	General		The clinical relevance is unclear	20619487; 21820097
SMARCAL1	11102	50485	Schimke immunoosseous dysplasia	AR	Pediatric		Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Renal	Allergy/Immunology/Infectious		Though the disorder may be clinically recognizable in many individuals, many individuals have an associated risk for opportunistic infection due to T-cell deficiency, and prophylaxis (eg, against P. carinii) and early and aggressive treatment of infections can be beneficial; BMT has been described	4282260; 2397176; 2066860; 8267014; 9674900; 9632175; 10528861; 10653321; 11113849; 0710226; 11799392; 12471207; 15523612; 16419127; 17089404; 17676601; 20301550 
SMARCB1	11103	6598	Schwannomatosis; Rhabdoid tumor predisposition syndrome	AD	Pediatric	Allelic with Mental retardation, autosomal dominant 15 (AD); Coffin-Siris syndrome (AD)	Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Genitourinary	Oncologic	Coffin-Siris syndrome can involve multiple congenital anomalies	Surveillance/early treatment of tumors may reduce morbidity	6091860; 2543225; 9737241; 10521299; 17357086; 18285426; 18072270; 19582488; 20930055; 22426308; 22038540 
SMARCE1	11109	6605	Meningioma, familial, susceptibility to	AD	Pediatric	Allelic with Coffin-Siris syndrome (AD)	Craniofacial; Musculoskeletal; Neurologic; Oncologic	Oncologic	Coffin-Siris syndrome can involve multiple congenital anomalies	Awareness of the risk of neoplasms may allow early detection and treatment	23377182; 25168959
SMC1A	11111	8243	Cornelia de Lange syndrome 2	XL	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16604071; 20358602; 20635401 
SMC3	2468	9126	Cornelia de Lange syndrome 3	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17273969; 24403048
SMCHD1	29090	23347	Facioscapulohumeral muscular dystrophy, type 2	Digenic (involving a SMCHD1 mutation and permissive D4Z4 haplotype)	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23143600
SMIM1	44204	388588	Blood group, Vel system	BG	Pediatric		Hematologic	Hematologic		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	23505126; 23563606; 23563608
SMN1	11117	6606	Spinal muscular atrophy, type I; Spinal muscular atrophy, type II; Spinal muscular atrophy, type III; Spinal muscular atrophy, type IV	AR	N/A	N/A	Musculoskeletal; Neurologic	General	Valproate has been reported as being beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7658877; 8551862; 7813012; 8968751; 8900234; 8782046; 8882869;  9245983; 10735271; 9056553; 10339583; 14705979; 17998484; 16775228; 18337729; 18941424; 19050931; 19716110; 1978076; 20301526
SMN2	11118	6607	Spinal muscular atrophy, modifier of	AD	N/A	N/A	Musculoskeletal; Neurologic	General	Variants are most important in the context of SMN1 mutations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8900234; 9245983; 11791208; 16508748; 18337729; 18662980; 19716110; 19780763; 20301526
SMOC1	20318	64093	Microphthalmia with limb anomalies	AR	N/A	N/A	Musculoskeletal; Ophthalmologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21194678; 21194680
SMOC2	20323	64094	Dentin dysplasia, type I	AR	N/A	N/A	Dental	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22152679; 23317772 
SMPD1	11120	6609	Niemann-Pick disease, type A; Niemann-Pick disease, type B	AR	N/A	N/A	Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Neurologic; Ophthalmologic; Pulmonary	General	It has been suggested that it could be useful to screen for NPB in heart disease clinics (for patients with very low HDL), or in endocrinology clinics (in individuals with growth retardation)	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	13516139; 2023926; 1301192; 1618760; 8664904; 12369017; 15877209; 16434659; 17360762; 17632693; 18815062; 19050888; 19405096; 20301544; 20386867; 22613662 
SMPX	11122	23676	Deafness, X-linked 4	XL	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic	Both prelingual and postlingual onset of deafness has been described, with males described as being affected earlier and more severely	Early recognition and treatment  of hearing impairment, which may occur in the prelingual stage in some individuals, may improve outcomes, including speech and language development	8872482; 21549336; 21549342; 21893181; 22911656
SMS	11123	6611	Mental retardation, X-linked, Snyder-Robinson type	XL	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	Musculoskeletal	As with other disorders that manifest with seizures, maximal seizure control is beneficial	Individuals manifest with osteoporosis, and calcium supplementation (with ectopic calcification monitoring) and awareness of fracture risk may be beneficial	5823961; 14508504; 18550699; 19206178; 19277733; 21318891; 22612257; 23696453; 23805436
SNAI2	11094	6591	Waardenburg syndrome, type 2D	AR	Pediatric	Allelic with Piebaldism (AD)	Audiologic/Otolaryngologic; Dermatologic; Ophthalmologic	Audiologic/Otolaryngologic	The condition may be recognizable from manifestations that may be apparent through physical examination	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	1717985; 9450866; 12444107; 12955764
SNAP29	11133	9342	Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (CEDNIK syndrome)	AR	N/A	N/A	Dermatologic; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15968592
SNCA	11138	6622	Parkinson disease; Dementia with Lewy bodies	AD	N/A	N/A	Neurologic	General	Levodopa can be beneficial in individuals with Parkinson disease	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2158268; 8285594; 9276199; 9197268; 11261505; 14593171; 14755720; 14755719; 16358335; 17251522; 18852448; 18413475; 18195271; 18852449; 18852445; 19139307; 19632874; 21412942; 21800132 
SNCAIP	11139	9627	Parkinson disease	AD	N/A	N/A	Neurologic	General	Levodopa can be beneficial in individuals with Parkinson disease; The pathogenicity of reported variants is unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12761037; 18366718
SNCB	11140	6620	Dementia with Lewy bodies	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15365127
SNIP1	30587	79753	Psychomotor retardation, epilepsy, and craniofacial dysmorphism	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22279524
SNRNP200	30859	23020	Retinitis pigmentosa 33	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16612614; 19878916; 21618346; 23029027
SNRPE	11161	6635	Hypotrichosis 11	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23246290
SNTA1	11167	6640	Long QT syndrome 12	AD	Adult		Cardiovascular	Cardiovascular		Surveillance (eg, with electrocardiography), preventive measures and medical management may be beneficial to decrease morbidity and mortality	10220144; 18591664
SNX10	14974	29887	Osteopetrosis, autosomal recessive 8	AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Dental; Hematologic; Musculoskeletal; Ophthalmologic	Musculoskeletal		The condition has been described as manifesting with sequelae of osteopetrosis, including  failure to thrive related to upper airway issues, as well as complications affecting multiple organ systems, and successful BMT in early childhood has been described	22499339; 23123320
SOBP	29256	55084	Mental retardation, anterior maxillary protrusion, and strabismus	AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17618476; 21035105
SOD1	11179	6647	Amyotrophic lateral sclerosis; Keratoconus	AD/AR	N/A	N/A	Neurologic; Ophthalmologic	General	Evidence for involvement with Keratoconus is unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Evidence for pathogenicity is unclear in Keratoconus	8351519; 8105280; 8446170; 7647793; 8592323; 7887412; 15623718; 20577002; 22264771; 22292843; 22292847; 22722621 
SOS1	11187	6654	Noonan syndrome 4	AD	Pediatric	Allelic with Fibromatosis, gingival (AD)	Cardiovascular; Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic 	Cardiovascular; Hematologic		Surveillance and treatment related to  manifestations such as cardiac anomalies (which include pulmonic stenosis and hypertrophic cardiomyopathy) can be beneficial; The condition can include bleeding diathesis,  and recognition and preventive measures (eg, in surgical situations) can be beneficial	11868160; 17143285; 17143282; 17586837; 18678287; 18925667; 19047498; 18456719; 19438935; 19077116; 20602484; 20876176; 20301303 
SOST	13771	50964	Craniodiaphyseal dysplasia, autosomal dominant; Sclerosteosis 1; van Buchem disease 	AD/AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal	Musculoskeletal		Starting in infancy, regular surveillance for sequelae related to overgrowth, including hearing evaluation, assessment of signs of increased intracranial pressure and cranial nerve entrapment, can allow early surgical management	13924477; 3276528; 6323069; 8433139; 9712543; 9463328; 11179006; 11836356; 12116252; 12694228; 14671168; 17245025; 17853455; 20301406; 20583295; 21221996
SOX10	11190	6663	Waardenburg syndrome, type 4C; Waardenburg syndrome, type 2E; Peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung disease	AD	Pediatric		Audiologic/Otolaryngologic; Dermatologic; Gastrointestinal; Genitourinary; Neurologic; Ophthalmologic	Audiologic/Otolaryngologic; Gastrointestinal		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In some individuals (such as with Peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung disease), awareness of potential GI complications (eg,  chronic intestinal pseudoobstruction) may be beneficial to allow prompt and appropriate management	8911608; 9462749; 10441344; 10077527; 12189494; 17999358; 18348267; 18627047; 22246888 
SOX11	11191	6664	Mental retardation, autosomal dominant 27	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24886874
SOX17	18122	64321	Vesicoureteral reflux 3	AD	Pediatric		Renal	Renal		Monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function	20960469
SOX18	11194	54345	Hypotrichosis-lymphedema-telangiectasia syndrome	AD/AR	N/A	N/A	Cardiovascular; Dermatologic; Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12740761
SOX2	11195	6657	Microphthalmia, syndromic 3	AD	Pediatric		Craniofacial; Dental; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	General	Individuals may demonstrate endocrine anomalies such as growth hormone deficiency, and early recognition and treatment may be beneficial	Individuals may demonstrate endocrine anomalies such as growth hormone deficiency, and early recognition and treatment may be beneficial	10564870; 12002146; 12612584; 12749061;  15346919; 16145681; 15389708; 15812812; 16283891; 16470798; 16932809; 16543359; 16892407; 19254784; 17219395; 18831064; 19921648; 20301477; 20301552; 20803647
SOX3	11199	6658	Panhypopituitarism, X-linked	XL	Pediatric	Allelic with Mental retardation, X-linked, with isolated growth hormone deficiency (XL), which may be recognizable, and early recognition may not necessarily be additionally helpful	Endocrine; Musculoskeletal; Neurologic	Endocrine	Deletions/duplications involving the SOX3 regulatory region can result in 46,XX sex reversal 3	Treatment for endocrine deficiencies, including those resulting in neonatal electrolyte abnormalities, may be beneficial	8826446;  9106538; 11031100; 12428212; 15800844; 17400794; 21183788 
SOX9	11204	6662	Campomelic dysplasia	XL	Pediatric	Allelic with 46,XX sex reversal 2 (AD), which has been reported as resulting from SOX9 promoter anomalies or cytogenetic aberrations	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Oncologic; Renal; Genitourinary	Oncologic; Genitourinary	The condition can involve multiple congenital anomalies	Individuals with a 46,XY karyotype and genital undermasculinization should undergo  gonadal removal due to risk of gonadoblastoma	10588843; 20301724; 21208124
SP110	5401	3431	Hepatic venoocclusive disease with immunodeficiency	AR	Pediatric		Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Neurologic	Allergy/Immunology/Infectious		Mortality is high if the condition is unrecognized; interventions include  intravenous immunoglobulin and infectious prophylaxis (Pneumocystis jerovici)	16648851; 17510920; 22621957; 22982295 
SP7	17321	121340	Osteogenesis imperfecta, type XII	AR	N/A	N/A	Dental; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20579626
SPARC	11219	6678	Keratoconus	AD	N/A	N/A	Ophthalmologic	General	Evidence for pathogenicity of the described variants is unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21976959
SPAST	11233	6683	Spastic paraplegia 4, autosomal dominant	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9302257; 9736780; 10699187; 11134375; 11843700; 11309678; 12471215; 15159500; 15210521; 15248095; 14872021; 16682546; 16055926; 16832076; 17345589; 17098887; 17895902; 18401025; 19652142; 18701882; 19939411; 20301339; 20562464; 20932283; 21659953; 21834905; 22192498; 22960362 
SPATA16	29935	83893	Spermatogenic failure 6	AR	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17847006
SPATA5	18119	166378	Schizophrenia	AD	N/A	N/A	Neurologic	General		Evidence or clinical applicability unclear	21822266
SPATA7	20423	55812	Leber congenital amaurosis 3; Retitinitis pigmentosa, juvenile, SPATA7-related	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9799089; 18936139; 19268277; 21310915
SPECC1L	29022	23384	Facial clefting, oblique, 1	AD	N/A	N/A	Craniofacial	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3398011; 21703590
SPEG	16901	10290	Centronuclear myopathy 5	AR	Pediatric		Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	Cardiovascular		The condition may include cardiomyopathy, and recognition may allow early management, which has been described as effectve in affected individuals	25087613
SPG11	11226	80208	Spastic paraplegia 11	AR	N/A	N/A	Neurologic	General	Levodopa has been described as beneficial in an individual who presented with features of parkinsonism	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17717710; 18067136; 17322883; 18663179; 18787847; 19196735; 19194956; 19513778; 20108361; 20301389; 20390432; 20571989; 20971220; 21035867; 21381113; 21625935;  22154821; 22175763; 23043354; 23121729
SPG20	18514	23111	Spastic paraplegia 20 (Troyer syndrome)	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6022528; 12134148; 18413476; 20437587
SPG21	20373	51324	Spastic paraplegia 21 (Mast syndrome)	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6024251; 14564668; 20301682; 24451228
SPG7	11237	6687	Spastic paraplegia 7, autosomal recessive	AR	N/A	N/A	Neurologic	General	Heterozygotes may demonstrate manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9635427; 9634528; 16534102; 18200586; 18799786; 20108356; 21623769; 22571692; 22964162 
SPINK1	11244	6690	Pancreatitis, hereditary	AD	Pediatric		Gastrointestinal; Oncologic	Gastrointestinal; Oncologic		Dietary measures (eg, low-fat diet with frequent feeding), hydration, and antioxidants, with avoidance of precipitants such as alcohol and tobacco, can beneficial in order to ameliorate episodes of pancreatitis; Individuals may be at high risk of pancreatic cancer, and awareness may allow early diagnosis and treatment	2813331; 10691414; 10835640; 11938439; 12011155; 16492714; 17274009; 20543535; 20664488; 21610753; 20676769; 21415673; 21375584; 20977904; 22228370
SPINK5	15464	11005	Netherton syndrome	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic	Allergy/Immunology/Infectious; Dermatologic 		The condition may not always be readily recognizable; Recurrent bacterial infections are common, and prophylactic measures, as well as prompt and aggressive treatment of infections may be beneficial; Hypernatremic dehydration in the neonatal period can result in severe sequelae, and awareness may allow preventive measures and prompt medical management	13582191; 7822652; 10835624; 11841556; 11693786; 17608759; 19683336; 20107740; 21573681; 21564178; 21692842; 22377713; 22837558; 23331056
SPINT2	11247	10653	Diarrhea 3, secretory sodium, congenital, with or without other congenital anomalies	AD	Pediatric		Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Ophthalmologic	Gastrointestinal		Due to fecal sodium loss, individuals may present with severe (potentially lethal) secretory diarrhea and related electrolyte/metabolic derangements, including hyponatremic metabolic acidosis, and recognition may allow appropriate medical management, which includes parenteral nutrition (weaning from parenteral nutrition, with oral sodium citrate supplementation, is possible in childhood	11113072; 17786112; 19185281; 20009592
SPR	11257	6697	Dystonia, Dopa-responsive, due to sepiapterin reductase deficiency	AR	Pediatric		Biochemical; Neurologic	Biochemical		The condition may be frequently mistaken for nonspecific findings such as idiopathic "cerebral palsy", and many individuals benefit from medical therapy (eg, levodopa/carbidopa, 5-hydroxytryptophan)	11443547; 7159114; 18502672; 19130291; 20222129; 21431957; 22291068; 22522443; 22018912 
SPRED1	20249	161742	Legius syndrome	AD	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General	Oncologic processes are reported in some individuals, but the overall risk is unclear, and it has been stated that the condition does not involve tumor predisposition	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17704776; 19366998; 19443465; 19920235; 20179001; 21649642; 21548021; 20945555; 22753041; 23401230
SPRY4	15533	81848	Hypogonadotropic hypogonadism 17, with or without anosmia	AD/Digenic	Pediatric		Audiologic/Otolaryngologic; Dental; Endocrine; Musculoskeletal; Neurologic	Endocrine	Relatively complex genetic models of disease have been described (eg, involving mutations in other FGF8-network-associated genes)	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	23643382
SPTA1	11272	6708	Spherocytosis, type 3; Pyropoikilocytosis , hereditary; Ellipsocytosis 2	AD/AR	Pediatric		Hematologic	Hematologic		Individuals have been described with severe hemolytic anemia, which has been treated by interventions such as frequent transfusions and splenectomy	1191563; 7070419; 2987946; 3785322; 3597773; 2567189; 2794061; 1541680; 8226774; 8941647; 16150946; 21251457 
SPTAN1	11273	6709	Epileptic encephalopathy, early infantile, 5	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18469812; 18065176; 20493457; 22258530
SPTB	11274	6710	Spherocytosis, type 2, Ellipsocytosis, type 3; Anemia, neonatal hemolytic	AD/AR	Pediatric		Hematologic	Hematologic		Some individuals may have severe, transfusion-requiring anemia, and splenectomy may also be beneficial	4426130; 7229027; 7119110; 7104494; 4052329; 3276733; 2807277; 2346784; 2070088; 1391962; 8102379; 8226774; 7883966; 8675627; 8844207; 9075575; 9005995; 9163587; 9414314; 9450796; 9609518; 9887280; 11703334; 19538529
SPTBN2	11276	6712	Spinocerebellar ataxia 5, autosomal dominant; Spinocerebellar ataxia 14, autosomal recessive	AD/AR	N/A	N/A	Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16429157; 23236289; 23838597
SPTLC1	11277	10558	Neuropathy, hereditary sensory and autonomic, type IA; Neuropathy, hereditary sensory and autonomic, type IC	AD	N/A	N/A	Neurologic	General	Oral l-serine has shown some benefitis in trials	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11242106; 11242114; 12417569; 15037712; 19132419; 20920666; 22045570; 22302274 
SQSTM1	11280	8878	Paget disease of bone	AD/AR	Pediatric		Audiologic/Otolaryngologic; Musculoskeletal; Oncologic	Musculoskeletal; Oncologic		Medical management (eg, inhibitors of osteoclastic bone resorption) can be beneficial -  bisphosphonates are the current first line of treatment; Awareness of the risk of related oncologic processes (eg, osteosarcoma) may be beneficial to allow early treatment	9626117; 11123042; 12374763; 11992264; 15176995; 18620951; 21735147; 22024254 
SRCAP	16974	10847	Floating-Harbor syndrome	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7588969; 16523514; 20358590; 22265015; 23763483
SRD5A2	11285	6716	Steroid 5-alpha-reductase 2 deficiency	AR	Pediatric		Endocrine; Genitourinary; Oncologic	Endocrine; Genitourinary; Oncologic		Hormonal treatment may be beneficial related to phenotypic gender characteristics; Due to risk of gonadal malignancy, prophlactic measures (related to gonadal tumors) may be beneficial	4432067; 431680; 1944596; 1406794; 1522235; 8262007; 7554313; 8626825; 8768837; 8606628; 8723114; 8789759; 9208814; 9066886; 9467575; 9745434; 10564874; 10999800; 10718838; 11869378; 12576851; 12699446; 12713261; 12843198; 15813602; 16098368; 16181229; 17551467; 18391525; 17609295; 18717241; 18314109; 18350250; 20511729; 20019388; 20132346; 20395661; 21147889; 20850730; 22001134; 22453073
SRD5A3	25812	79644	Kahrizi syndrome; Congenital disorder of glycosylation, type Iq	AR	Pediatric	 	Biochemical; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Hematologic; Neurologic; Ophthalmologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	18271001; 18781183; 20637498; 20700148
SRP72	11303	6731	Bone marrow failure syndrome 1	AD	Pediatric		Audiologic/Otolaryngologic; Hematologic; Oncologic	Audiologic/Otolaryngologic; Hematologic; Oncologic		Individuals have been described as having early-onset anemia/panyctopenia, as well as later myelodysplasia, and measures to detect and ameliorate hematologic findings  may be beneficial; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	22541560
SRPX2	30668	27286	Rolandic epilepsy, mental retardation, and speech dyspraxia	XL	N/A	N/A	Neurologic	General	The evidence of mutations as being related to disease causation has been questioned due to subsequent population-based studies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16497722; 23871722; 24995671
SRY	11311	6736	46,XY disorder of sex development; 46, XX disorder of sex development	YL	Pediatric		Endocrine; Genitourinary; Oncologic	Genitourinary; Oncologic	Treatment depends on sex chromosome complement; Hormonal treatment may be beneficial (eg, with hormone replacement therapy at the onset of puberty)	In individuals with 46, XY, karyotype, due to increased risk for gonadal tumors, abdominal dysgenetic gonads and streak gonads should be surgically removed	2247151; 7904700; 8472885; 1956279; 1734522; 1639410; 1570829; 20301714; 20301589 
SSR4	11326	6748	Congenital disorder of glycosylation, type Iy	XL	N/A	N/A	Biochemical; Craniofacial; Musculoskeletal; Neurologic	General	Hepatic-metabolized agents should be avoided	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24218363
SSTR5	11334	6755	Resistance to somatostatin treatment	AD	Pediatric	 	General	Pharmacogenomic		The presence of variants may impact the use of medications to treat conditions such as acromegaly	11502816; 15914528; 21744088; 21810856
ST14	11344	6768	Ichthyosis, congenital, autosomal recessive 11	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17273967; 18445049; 18843291
ST3GAL3	10866	6487	Mental retardation, autosomal recessive 12; Epileptic encephalopathy, early infantile, 15	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17120046; 21907012; 23252400 
ST3GAL5	10872	8869	Ganglioside GM3 synthase deficiency	AR	N/A	N/A	Dermatologic; Neurologic; Ophthalmologic	General	Treatment with ubiquinone has been described, but the overall efficacy is unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4213132; 15502825; 22990144; 23436467
STAG3	11356	10734	Premature ovarian failure 8	AR	Pediatric		Endocrine; Obstetric	Obstetric	One described individual was reported as additionally affected by ovarian cancer	Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency	22428046; 24597867
STAMBP	16950	10617	Microcephaly-capillary malformation syndrome	AR	N/A		Dermatologic; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23542699
STAR	11359	6770	Lipoid adrenal hyperplasia	AR	Pediatric		Endocrine; Genitourinary;  Oncologic	Endocrine; Genitourinary; Oncologic		Due to the severity of disease, most individuals present as phenotypic females with fatal salt-wasting adrenal crises if untreated in early infancy (patients may also present later in life with milder forms of disease), and medical treatment (eg, with glucocorticoid and mineralcorticoid replacement) may be beneficial; Treatment of genitourinary anomalies (eg, with surgery, including related to the risk of malignancy in genotypic males) may be indicated in some individuals	13968788; 4685387; 3841304; 2419119; 1661294; 7892608; 7547998; 8948562; 9077535; 10323391; 11061515; 16968793; 21057961; 21691971; 21714456; 21846663; 22028173; 22083155; 22249004
STAT1	11362	6772	Immunodeficiency 31A; Immunodeficiency 31B; Immunodeficiency 31C	AD/AR	Pediatric		Allergy/Immunology/Infectious; Oncologic	Allergy/Immunology/Infectious; Oncologic		Individuals with autosomal recessive forms demonstrate susceptibility to severe viral and mycobacterial infections (including lethal infections), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals with heterozygous forms may be  susceptible to candiasis, and may be susceptible to neoplasms including carcinoma, as well as autoimmune thyroid disease, and awareness may allow prompt diagnosis and treatment	11452125; 12590259; 16585605; 21727188; 21714643; 22437822; 22730530; 22748593; 22847544 
STAT3	11364	6774	Hyper-IgE recurrent infection syndrome; Autoimmune disease, multisystem, infantile onset	AD	Pediatric		Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Musculoskeletal; Oncologic	Allergy/Immunology/Infectious; Cardiovascular; Oncologic		In Hyper-IgE recurrent infection syndrome, among other manifestations, individuals may suffer recurrent mucocutaneous and pulmonary infections, and antintiinfectious prophylaxis (eg, antibiotics, antifungals, and IgG infusions), as well as early and aggressive treatment of infections may be beneficial; The condition may include vascular anomalies, and awareness may be beneficial in management; Individuals may also have susceptibility to malignancies such as non-Hodgkin lymphoma, and awareness may allow early diagnosis and treatment; In Autoimmune disease, multisystem, infantile onset, individuals have been described with immunodeficiency, and awareness may allow antiinfectious prophylaxis as well as early and aggressive treatment of infections; Awarness of sequelae of autoimmune disease (eg, resulting in hypothyroidism) may allow early management of such manifestations	4161105; 5059313; 6806658; 10053178; 17881745; 17676033; 17942886; 21703716; 22084479; 22751495; 25038750
STAT5B	11367	6777	Growth hormone insensitivity with immunodeficiency	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal	Allergy/Immunology/Infectious; Endocrine	Heterozygotes may demonstrate some manifestations (eg, short stature)	Individuals demonstrate infection susceptibility, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; As relates to growth deficiency, treatment with recombinant human IGF-I may be beneficial	8977385; 13679528; 15827093; 17030597; 16787985; 17389811; 21396575; 22423513; 22678306 
STEAP3	24592	55240	Hypochromic microcytic anemia with iron overload 2	AD	Pediatric		Endocrine; Hematologic	Endocrine; Hematologic		Individuals have been described with transfusion-dependent anemia; The condition may involve primary endocrine anomalies, and surveillance for involvement (eg, adrenal failure or thyroid insufficiency) may benefit medical management	22031863
STIL	10879	6491	Microcephaly, primary autosomal recessive, 7	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19215732; 20978018; 25218063
STIM1	11386	6786	Stormorken syndrome; Immunodeficiency 10	AD/AR	Pediatric	Allelic with Myopathy, tubular aggregate 1 (AD)	Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Dental; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Cardiovascular; Hematologic		In Stormorken syndrome, individuals may demonstrate hematologic anomalies including anemia, thrombocytopenia, and bleeding diathesis, and awareness may allow preventive measures and prompt treatment; Individuals have been described with cardiovascular anomalies (eg, intracranial aneurysms), and awareness may allow surveillance and early management; In Immunodeficiency 10, individuals may suffer early and severe (including fatal) infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals may have hematologic abnormalities, including autoimmune hemolytic anemia and thrombocytopenia, which have been reported as steroid-responsive; HSCT has been reported	19420366; 20876309; 22190180; 23332920; 24570283; 24591628; 24619930
STK11	11389	6794	Peutz-Jeghers syndrome	AD	Pediatric		Dermatologic; Gastrointestinal; Oncologic	Gastrointestinal; Oncologic		Routine surgical/endoscopic procedures can decrease the need of emergent procedures for sudden and severe sequelae (eg, intussusception); Surveillance for and early treatment of a variety of common malignancies (individuals may be at increased risk of a number of types of epithelial malignancies, including breast, cervical adenoma malignum, colorectal, gastric, ovarian, pancreatic cancers, sex cord tumors with annular tubules, and testicular Sertoli cell tumors) can be beneficial	15399020; 14214503; 14279723; 5466889; 990720; 7436458; 3943856; 3697923; 3587280; 3181678; 2599445; 1986290; 7776109; 7802138; 9850045; 9428765; 9425897; 10408777; 10689645; 10874301; 11389158; 12044140; 15121768; 15200509; 15863673; 15617552; 20581245; 20301443 
STK4	11408	6789	T-cell immunodeficiency syndrome, recurrent infections, autoimmunity, with or without cardiac malformations	AR	Pediatric		Allergy/Immunology/Infectious; Cardiovascular	Allergy/Immunology/Infectious; Cardiovascular		Individuals are susceptible to recurrent and severe viral, bacterial, and fungal infections (as well as sequelae such as EBV-related lymphoma), and and prophylaxis, as well as prompt and aggressive treatment of infections may be beneficial; Individuals may have cardiovascular anomalies, and surveillance (including with echocardiogram) may allow early detection and management; HSCT has been described	22294732; 22174160
STRA6	30650	64220	Microphthalmia, syndromic 9; Microphthalmia, isolated, with coloboma 8	AR	N/A	N/A	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary; Renal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11857549; 17503335; 17236193; 17273977; 19112531; 19213032; 19309693; 21901792; 22283518; 22686418 
STRADA	30172	92335	Polyhydramnios, megalencephaly, and symptomatic epilepsy	AR	N/A	N/A	Cardiovascular; Endocrine; Neurologic; Obstetric; Renal	General	The condition can involve multiple congenital anomalies and can affect the pregnancy (due to polyhydramnios) with the affected individual	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17522105
STRC	16035	161497	Deafness, autosomal recessive 16	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	9429146; 10090914; 11687802; 21686705; 19246478 
STS	11425	412	Steroid sulfatase deficiency	XL	Pediatric		Biochemical; Dermatologic; Obstetric; Oncologic; Ophthalmologic; Genitourinary	Obstetric; Oncologic; Genitourinary		In pregnancy, affected females may manifest with birth/delivery complications, such as failure to progress in labor, and awareness may allow improved planning and management of pregnancy and delivery; Individuals are at risk for testicular cancer, and awareness may allow preventive measures/early management, which may decrease morbidity and mortality	3864397; 5303230; 5307231; 6135610; 6140547; 6234482; 6652948; 6135610; 6929654; 6482910; 2866054; 3480263; 3480541; 3032454; 1539590; 7546451; 9252398; 10583107; 10692123; 11477606; 16191859; 16403384; 18076704; 19200188; 20236202; 21530180; 22419362; 22486194; 23442483
STT3A	6172	3703	Congenital disorder of glycosylation, type Iw	AR	N/A	N/A	Biochemical; Neurologic	General	Hepatic-metabolized agents should be avoided	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23842455
STT3B	30611	201595	Congenital disorder of glycosylation, type Ix	AR	N/A	N/A	Biochemical; Gastrointestinal; Genitourinary; Hematologic; Neurologic; Ophthalmologic	Hematologic	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	23842455
STUB1	11427	10273	Spinocerebellar ataxia, autosomal recessive 16	AR	N/A	N/A	Neurologic	General	Hypogonadism has been described in some individuals	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24312598; 24113144; 24719489; 24742043; 25258038
STX11	11429	8676	Hemophagocytic lymphohistiocytosis, familial, 4	AR	Pediatric		Allergy/Immunology/Infectious; Neurologic; Oncologic	Allergy/Immunology/Infectious; Oncologic	Some individuals have been described as having remission without treatment; It has been suggested that mutations may also confer risk for other malignancies.	Antibiotics or antiviral agents can be beneficial to treat/prevent infections that can trigger an exaggerated inflammatory response. Chemo/immunotherapy can achieve clinical stability prior to allogeneic hematopoietic cell transplantation (HCT), the only curative therapy.	15703195; 16278825; 16582076; 24459464
STX16	11431	8675	Pseudohypoparathyroidism, type IB	AD	Pediatric		Endocrine; Renal	Endocrine; Renal		Complications such as osteitis fibrosa cystica may be effectively treated with calcium and vitamin D therapy	15537666; 17595244; 18626245; 20960161; 20538864; 21752878 
STXBP1	11444	6812	Epileptic encephalopathy, early infantile 4	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18469812; 18065176; 19557857; 20876469; 21062273; 21376300; 21762454; 21770924; 22596016; 23020937; 24623842
STXBP2	11445	6813	Hemophagocytic lymphohistiocytosis, familial 5	AR	Pediatric		Allergy/Immunology/Infectious; Neurologic	Allergy/Immunology/Infectious		Antibiotics or antiviral agents can be beneficial to treat/prevent infections that can trigger an exaggerated inflammatory response. Chemo/immunotherapy can achieve clinical stability prior to allogeneic hematopoietic cell transplantation (HCT), the only curative therapy.	19804848; 19884660; 20798128 
SUCLA2	11448	8803	Mitochondrial DNA depletion syndrome 5	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Audiologic/Otolaryngologic	Features such as frequent infections and cardiomyopathy have been described in some individuals	Early recognition and treatment (eg, with cochlear implants) of hearing impairment, which may occur in the prelingual stage, may improve outcomes, including speech and language development	15877282; 19015156; 17301081; 17287286; 19015156; 19666145; 20301762; 23010432 
SUCLG1	11449	8802	Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria)	AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17668387; 19526370; 20693550; 21093335; 21639866 
SUFU	16466	51684	Medulloblastoma; Basal cell nevus syndrome	AD	Pediatric		Dermatologic; Oncologic	Oncologic		Individuals are at risk for a number of types of malignancies (including medulloblastoma), and surveillance may allow early diagnosis and treatment (including with molecular therapies that target the Hedgehog signaling pathway), potentially reducing morbidity and mortality; Avoidance of agents such as radiation therapy is indicated	12068298; 19533801; 19833601; 21188540; 22670903; 22670904
SUGCT	16001	79783	Glutaric aciduria III	AR	N/A	N/A	Biochemical	General	The clinical significance of the condition is unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1909402; 12555941; 18926513
SUMF1	20376	285362	Multiple sulfatase deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14476546; 11737681; 12757706; 12757705; 17657823; 18509892; 19066960; 19697114; 21224894
SUMO1	12502	7341	Orofacial cleft 10	AD	N/A	N/A	Craniofacial	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16990542
SUOX	11460	6821	Sulfocysteinuria	AR	Pediatric		Biochemical; Neurologic; Ophthalmologic	Biochemical		Dietary measures (eg, low protein diet and synthetic amino acid mixture without cystine or methionine) have been described as beneficial in early reports	302914; 509724; 9428520; 10682307; 15952210; 12368985; 19793632 
SURF1	11474	6834	Leigh syndrome	AR	N/A	N/A	Biochemical; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9837813; 9843204; 10443880; 10556302; 10746561; 11317352; 11804207; 12538779; 14557577; 15214016; 16326995; 17908801; 18583168; 19780766; 21937992 
SYCP3	18130	50511	Spermatogenic failure 4	AD	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14643120; 19110213
SYN1	11494	6853	Epilepsy, X-linked, with variable learning disabilities and behavior disorders	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14985377
SYNE1	17089	23345	Emery-Dreifuss muscular dystrophy 4, autosomal dominant; Spinocerebellar ataxia, autosomal recessive 8	AD/AR	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular		One reported patient was found to have left ventricular basal and septal hypertrophy with mild diastolic dysfunction, and surveillance (eg, with echocardiogram) may allow early medical management	17503513; 17159980; 17761684; 19542096; 20301553; 20301609
SYNE2	17084	23224	Emery-Dreifuss muscular dystrophy 5, autosomal dominant	AD	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular		Reported patients had cardiac findings such as arrhythmia, left ventricular hypertrophy, and dilated cardiomyopathy, and surveillance may allow early diagnosis and treatment; Heart transplantation has been reported	17761684
SYNE4	26703	163183	Deafness, autosomal recessive, 76	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	23348741
SYNGAP1	11497	8831	Mental retardation, autosomal dominant 5	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19196676; 23020937
SYP	11506	6855	Mental retardation, X-linked 96	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19377476
SYT14	23143	255928	Spinocerebellar ataxia, autosomal recessive 11	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21835308
SYT2	11510	127833	Myasthenic syndrome, presynaptic, congenital, with or without motor neuropathy	AD	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	25192047
SZT2	29040	23334	Epileptic encephalopathy, early infantile, 18	AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21835308; 23932106
T	11515	6862	Chordoma	AD	Pediatric	Allelic with Sacral agenesis with vertebral anomalies (AR)	Gastrointestinal; Musculoskeletal; Oncologic; Renal	Oncologic	Variants include duplications, and certain SNPs may confer a relatively high odds ratio; Sacral agenesis with vertebral anomalies can involve multiple congenital anomalies	Surveillance for neoplasms could potentially be beneficial in order to allow early detection and treatment	8733136; 10204846; 10332959; 10817656; 12116228; 15449172; 19801981; 23064415; 24253444
TAB2	17075	23118	Congenital heart defects, multiple types, 2	AD	Pediatric		Cardiovascular	Cardiovascular		While some reported cardiac malformations may be readily clinically ascertained, other reported types may be more subtle, and targeted surveillance (eg, with echocardiography and electrocardiography) for findings that have been reported as including bicuspid aortic valve and aortic dilatation, left ventricular outflow obstruction, subaortic stenosis, and atrial fibrillation, may allow early medical and/or surgical management, which may decrease morbidity and mortality	20493459
TAC3	11521	6866	Hypogonadotropic hypogonadism	AR	Pediatric		Endocrine	General	Hormonal treatment (eg, with chorionic gonadotropin) can induce and maintain secondary sex characteristics, and can allow reproduction	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19079066
TACO1	24316	51204	Mitochondrial complex IV deficiency	AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19503089
TACR3	11528	6870	Hypogonadotropic hypogonadism	AR	Pediatric		Endocrine	Endocrine		In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	19079066; 20301509
TACSTD2	11530	4070	Corneal dystrophy, gelatinous drop-like	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10192395; 12614764; 19693293; 20806038; 21541270 
TAF1	11535	6872	Dystonia 3, torsion, X-linked	XL	N/A	N/A	Neurologic	General	The condition may be responsive to levodopa	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15596620; 17273961
TAF2	11536	6873	Mental retardation, autosomal recessive 40	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21937992; 24084144
TAF4B	11538	6875	Spermatogenic failure 13	AR	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24431330
TALDO1	11559	6888	Transaldolase deficiency	AR	N/A	N/A	Biochemical; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11283793; 15877206; 17095351; 19401148; 21119539
TAP1	43	6890	Bare lymphocyte syndrome, type I	AR	Pediatric		Allergy/Immunology/Infectious; Pulmonary	Allergy/Immunology/Infectious; Pulmonary	The condition has been reported as possibly related to increased risk of malignancy as well as infectious manifestations	Individuals may manifest with frequent and severe infections (including early-onset severe bacterial infections), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; For pulmonary manifestations, treatment recommendations analogous to those in individuals cystic fibrosis have been recommended; Immunosuppressive therapy may be contraindicated	3891604; 10074495; 10074494; 10931128; 17498556; 17982230; 17315195; 18668571 
TAP2	44	6891	Bare lymphocyte syndrome, type I	AR	Pediatric		Allergy/Immunology/Infectious; Pulmonary	Allergy/Immunology/Infectious; Pulmonary	The condition has been reported as possibly related to increased risk of malignancy as well as infectious manifestations	Individuals may manifest with frequent and severe infections (including early-onset severe bacterial infections), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; For pulmonary manifestations, treatment recommendations analogous to those in individuals cystic fibrosis have been recommended; Immunosuppressive therapy may be contraindicated	7517574; 10074495; 10931128; 12644316; 17879436; 17879452; 20083708 
TAPBP	11566	6892	Bare lymphocyte syndrome, type I	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Although the described individual did not have the same types of infections as other individuals with TAP deficiency, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	10074495; 12149238 
TARDBP	11571	23435	Amyotrophic lateral sclerosis 10, with or without frontotemporal dementia	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17036243; 18288693; 18309045; 18372902; 18396105; 18438952; 18779421; 19224587; 19350673; 19609911; 20697052; 21220647; 21956716; 22292843; 22398199; 22456481; 22539580; 22722621 
TARS2	30740	80222	Combined oxidative phosphorylation deficiency 21	AR	N/A	N/A	Biochemical; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24827421
TAS2R38	9584	5726	Thiourea tasting; Phenylthiocarbamide tasting	AD	N/A	N/A	Neurologic	General		In Thiourea tasting; Phenylthiocarbamide tasting, the clinical applicability is unclear, though it has been suggested that variants may have  health-related manifestations (eg, involving nicotine and alcohol use)	17830260; 12595690; 16086309; 17250611; 18524836; 22130969 
TAT	11573	6898	Tyrosinemia, type II	AR	Pediatric		Biochemical; Dermatologic; Neurologic; Ophthalmologic	Biochemical		Dietary measures (controlled intake of phenylalanine and tyrosine) can be effective, including as relates to neurocognitive outcome	18901242; 33934; 6446465; 1356171; 1357662; 8912606; 12227462; 9544843; 16574453; 16917729; 18945316; 21145993; 21636300 
TAZ	11577	6901	3-Methylglutaconic aciduria, type II (Barth syndrome)	XL	Pediatric		Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	Allergy/Immunology/Infectious; Cardiovascular		Surveillance for cardiomyopathy and early medical treatment may reduce morbidity; in some individuals, early cardiac transplant may be necessary; Individuals can also have neutropenia, and prophylaxis against infections, with early and aggressive management of infections may be beneficial	6142097; 2372897; 1998334; 1719174; 8434619; 8487269; 7616547; 8630491; 9332651; 9382097; 9382096; 9345098; 11238270; 11735032; 12468278; 12032589; 15098233; 7394203; 19648820; 20301486; 20812380; 22410210; 21987083
TBC1D20	16133	128637	Warburg micro syndrome 4	AR	N/A	N/A	Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24239381
TBC1D24	29203	57465	Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome; Deafness, autosomal recessive 86	AD/AR	Pediatric	Allelic with Deafness, autosomal dominant, 65; Myoclonic epilepsy, infantile, familial (AR); Early infantile epileptic encephalopathy 16 (AR)	Audiologic/Otolaryngologic; Dermatologic; Musculoskeletal; Neurologic	Audiologic/Otolaryngologic	As with many disorders involving seizure risk, optimal control is beneficial, and genetic diagnosis may be beneficial related to medication selection	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	10741954; 20797691; 20727515; 21087195; 22211675; 23343562; 23526554; 24291220; 24387994; 24729539; 24729547
TBC1D4	19165	9882	Diabetes mellitus, noninsulin-dependent 5	AR	N/A	N/A	Endocrine	General	Heterozygous carriers may also display mild effects related to glucose metabolism	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	25043022
TBC1D7	21066	51256	Macrocephaly/megalencephaly syndrome, autosomal recessive	AR	N/A	N/A	Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23687350; 24515783
TBCE	11582	6905	Kenny-Caffey syndrome, type 1; Hypoparathyroidism-retardation-dysmorphism syndrome	AR	Pediatric		Endocrine; Musculoskeletal; Neurologic	Endocrine		Individuals can present with sequelae of neonatal hypocalcemia, and prompt diagnosis and treatment can lead to correction of electrolyte abnormalities; Some individuals with multiple pituitary anomalies (eg, affecting GH, cortisol, and including features of hypogonadotropic hypogonadism have been described), and surveillance may allow early diagnosis and treatment	2843457; 1701077; 2001103; 1308349; 7538982; 9056548; 12389028; 19491227; 19554981 
TBK1	11584	29110	Herpes simplex encephalitis	AD	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may be susceptible to severe herpes simplex virus infections includingherpes encephalitis has been described, and awareness may allow early diagnosis and treatment, potentially decreasing morbidity and mortality	22851595
TBP	11588	6908	Spinocerebellar ataxia 17	AD/AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10484774; 11448935; 11313753; 11914409; 11939898; 12805114; 15521976; 14985389; 15313853; 15365789; 20587494; 21108634; 21710129 
TBX1	11592	6899	Conotruncal anomaly face syndrome; Tetralogy of Fallot	AD	N/A	N/A	Cardiovascular; Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14585638; 16684884; 17273972; 17377518; 19948535; 20937753
TBX15	11594	6913	Cousin syndrome	AR	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7103674; 19068278
TBX19	11596	9095	Adrenocorticotropic hormone deficiency	AR	Pediatric		Endocrine	Endocrine		Individuals may have severe neonatal hypoglycemia, and treatment of adrenocortical insufficiency (eg, with hydrocortisone, fludricortisone) can be effective	4295129; 6314808; 2830787; 8222301; 11290323; 15613420
TBX20	11598	57057	Atrial septal defect 4	AD	Pediatric		Cardiovascular	Cardiovascular		Mutations can result in a wide spectrum of cardiac-related disease, some of which may be challenging to recognize, and awareness may allow early medical and/or surgical management of manifestations, which can include valvular disease and cardiomyopathy in addition to frank structural anomalies such as ASD	17668378; 19762328
TBX22	11600	50945	Cleft palate with or without ankyloglossia	XL	N/A	N/A	Craniofacial	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11559848; 12374769; 14729838; 15602089; 17846996; 17868388; 21248356; 22784330
TBX3	11602	6926	Ulnar-Mammary syndrome	AD	N/A	N/A	Cardiovascular; Dental; Endocrine; Genitourinary; Musculoskeletal; Renal	Cardiovascular	The condition can involve multiple congenital anomalies	Cardiac anomalies, including arrhythmias, have been reported, and surveillance may allow early detection and management	9207801; 12116211; 12668170; 19938096; 21199695 
TBX4	11603	9496	Small patella syndrome	AD	N/A	N/A	Musculoskeletal	General	Mutations have been reported as associated with childhood-onset pulmonary artery hypertension	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15106123; 23592887
TBX5	11604	6910	Holt-Oram syndrome	AD	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular		While the condition may be recognizable in the majority, individuals may have cardiac conduction abnormalities even without known cardiac malformations, and surveillance (eg, with electrocardiography) may allow early detection and management	14402857; 8730285; 8911604; 8988165; 8988164; 10077612; 10842287; 12818525; 17366586; 18818409; 20301290 
TBX6	11605	6911	Spondylocostal dysostosis 5, autosomal dominant	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23335591
TBXA2R	11608	6915	Bleeding disorder, platelet-type 13, susceptibility to	AD	Pediatric		Hematologic	Hematologic; Pharmacogenomic	Heterozygosity may cause abnormal in vitro platelet functional responses, but do not cause in vivo clinically significant dysfunction; Susceptibility is inherited in an autosomal dominant pattern, but clinical features, including mild mucocutaneous bleeding, occur only in the presence of a 'second hit' affecting platelet function	Surveillance and prompt treatment of bleeding diatheses may be beneficial; Avoidance of agents that may provoke or worsen bleeding episodes is warranted	7929844; 19828703; 21070398; 22101342 
TBXAS1	11609	6916	Ghosal hematodiaphyseal syndrome	AR	Pediatric		Hematologic; Musculoskeletal; Neurologic 	Hematologic		Steroid therapy has been described as effective for some hematologic manifestations	3385529; 2715908; 8444247; 17203301; 18264100
TCAP	11610	8557	Cardiomyopathy, dilated, 1N; Cardiomyopathy, hypertrophic; Muscular dystrophy, limb-girdle, type 2G	AD/AR	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular	The reported onset of heart failure has been in the adult period (including in young adults), but surveillance and early treatment may be indicated prior to adulthood; A mutation has been described in an individual with intestinal pseudo-obstruction, but it is not clear if early (genetic) diagnosis would be beneficial	Surveillance (eg, with echocardiography/electrocardiography) and preventive management may ameliorate/prevent severe sequelae	9245996; 10655062; 12507422; 15582318; 16352453; 16650785; 16490376; 19412328; 18408010; 22029105; 21530252 
TCF12	11623	6938	Craniosynostosis 3	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23354436
TCF4	11634	6925	Pitt-Hopkins syndrome	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	728011; 17436254; 17478476; 17436255; 18728071; 19235238; 19938247; 22045651
TCIRG1	11647	10312	Osteopetrosis, autosomal recessive 1	AR	Pediatric		Audiologic/Otolaryngologic; Dental; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	Hematologic; Musculoskeletal	Milder forms of disease, possibly due to heterozygous mutations have been described	Although the disorder may be frequently recognizable, medical treatments (eg, calcitriol, interferon gamma-1b) as well as surgical interventions may be beneficial; Early and aggressive treatment of infectious and hematologic manifestations, as well as neonatal hypocalcemia, which can result in tetanic seizures, may be beneficial; Awareness of multi-organ system complications may allow surveillance and prompt interventions; BMT/HSCT has been described	13532685; 4170880; 6986555; 6546410; 2877234; 1320672; 8291528; 7996361; 7753137; 10888887; 10942435; 12566520; 20870624; 20424301; 21042819; 23329773; 23412864
TCN2	11653	6948	Transcobalamin II deficiency	AR	Pediatric		Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Hematologic; Neurologic	Allergy/Immunology/Infectious; Biochemical		The condition can include neurocognitive impairment, hematologic anomalies (eg, anemia, panyctopenia), susecptibility to recurrent and severe infcections, and gastrointestinal sequelae, and cobalamin treatment can result in prevention and/or clinical improvement, including related to developmental parameters; Awareness of immunodeficiency may allow prompt treatment of infections	5096637; 4138209; 128427; 3143215; 309761; 1743216; 7849710; 19373259
TCOF1	11654	6949	Treacher Collins syndrome 1	AD	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Ophthalmologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	8563749; 8875242; 8894686; 9042910; 9096354; 11013442; 14598341; 15150774; 15214011; 15340364; 19050407; 19067896; 19572402; 20301704; 22317976; 22729243
TCTN1	26113	79600	Joubert syndrome 13	AR	N/A	N/A	Neurologic	General	The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20301500; 21725307
TCTN2	25774	79867	Meckel syndrome 8	AR	N/A	N/A	Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Renal	General	The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21462283; 20301500 
TCTN3	24519	26123	Joubert syndrome 18; Orofaciodigital syndrome IV (Mohr-Majewski syndrome)	AR	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Renal	General	The condition can include cardiac, renal, and other manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22883145
TDGF1	11701	6997	Forebrain anomalies; Congenital cardiac malformations	AD	N/A	N/A	Craniofacial; Cardiovascular; Endocrine; Neurologic	General	Individuals with forebrain anomalies such as holoprosencephaly  may demonstrate endocrine anomalies, including diabetes insipidus	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12073012; 18538293 
TDP1	18884	55775	Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12244316
TDRD7	30831	23424	Cataract, autosomal recessive congenital 4	AR	Pediatric		Ophthalmologic	Ophthalmologic; Pharmacogenomic		 Some affected family members developed glaucoma with open-angle and increased intraocular pressure following cataract extraction; Agents that may contribute to glaucoma should be avoided	21436445
TEAD1	11714	7003	Sveinsson choreoretinal atrophy	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15016762
TECPR2	19957	9895	Spastic paraplegia 49, autosomal recessive	AR	N/A	N/A	Craniofacial; Gastrointestinal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23176824
TECR	4551	9524	Mental retardation, autosomal recessive 14	AR	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11590547; 18446860; 21212097
TECTA	11720	7007	Deafness, autosomal recessive 21; Deafness, autosomal dominant 8/12	AD/AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	9150164; 9718342; 9763681; 10987647; 9590290; 9949200; 11333869; 12746400; 17661817; 17431902; 23226338 
TEK	11724	7010	Venous malformations, multiple cutaneous and mucosal	AD	Pediatric		Cardiovascular	Cardiovascular		Though infrequent, some individuals have venous malformations (including vascular neoplasms) within internal organs that could lead to severe sequelae; Cardiac malformations have also been described in a few individuals	7833915; 7783168; 8980225; 10369874; 19888299
TENM1	8117	10178	Microphthalmia, isolated, with coloboma 9	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22766609
TENM3	29944	55714	Microphthalmia, isolated, with coloboma 9	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22766609
TERC	11727	7012	Dyskeratosis congenita, autosomal dominant; Aplastic anemia; Pulmonary fibrosis and/or bone marrow failure, telomere-related 2	AD	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic;  Oncologic; Pulmonary	Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary	The presence of mutations has also been reported as increasing risk of malignancy, including melanoma	In dyskeratosis congenita, the presentation many not always be classic, and individuals are at high risk for hematologic anomalies (including bone marrow failure) and malignancy, and surveillance and prompt diagnosis and treatment may be beneficial; In Aplastic anemia, surveillance and prompt treatment of aplastic anemia and bone marrow failure may reduce morbidity; For treatment related to pulmonary fibrosis, immunotherapy may be beneficial, though lung transplantation may be indicated in individuals with severe/refractory disease	11574891; 12090986; 14630445; 17392301; 18753630; 19760749; 21436073; 22341970; 20301779; 23348503
TERT	11730	7015	Aplastic anemia; Dyskeratosis congenita, autosomal dominant; Dyskeratosis congenita, autosomal recessive; Pulmonary fibrosis and/or bone marrow failure, telomere-related 1	AD/AR	Pediatric		Allergy/Immunology/Infectious; Cardiovascular; Dental; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic;  Oncologic; Pulmonary	Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary		In dyskeratosis congenita, the presentation many not always be classic, and individuals are at high risk for hematologic anomalies (including bone marrow failure) and malignancy, and surveillance and prompt diagnosis and treatment may be beneficial; In Aplastic anemia, surveillance and prompt treatment of aplastic anemia and bone marrow failure may reduce morbidity; HSCT may be effective; For treatment related to pulmonary fibrosis, immunotherapy may be beneficial, though lung transplantation may be indicated in individuals with severe/refractory disease	16247010; 15814878; 16890917; 17392301; 17785587; 17460043; 18460650; 18042801; 19760749; 21602826; 20502709; 21436073; 22512499; 20301779
TF	11740	7018	Atransferrinemia	AR	Pediatric		Hematologic	Hematologic		The condition, which involves microcytic anemia and iron overload, can have insidious, nonspecific, and severe manifestations that may include congestive heart failure, and treatment with plasma infusion has been described as effective	13906010; 4625559; 8317485; 11110675; 15466165; 18097132; 19579082 
TFAP2A	11742	7020	Branchiooculofacial sydrome	AD	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	Audiologic/Otolaryngologic	The condition may be recognizable due to the presence of a specific pattern of congenital malformations affecting hearing as well as multiple organ systems; An individual with medulloblastoma has been described	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	1619642; 7747785; 9761567; 18423521; 19685247; 19764023; 19206157; 20358615; 20635357; 21634087; 21204207 
TFAP2B	11743	7021	Char syndrome; Patent ductus arteriosus, familial, nonsyndromic	AD	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	728571; 1342853; 8326495; 7645594; 9217229; 10368122; 10802654; 10955477; 11102923; 11505339; 15684060; 18752453; 21643846 
TFG	11758	10342	Hereditary motor and sensory neuropathy, proximal type; Spastic paraplegia 57	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17906970; 22883144; 23479643; 23553329; 25098539
TFR2	11762	7036	Hemochromatosis, type 3	AR	Pediatric		Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic	Biochemical; Gastrointestinal; Hematologic	Variants may also modify  hemochromatosis due to mutations in other genes (eg, HFE)	Preventive measures and treatment of iron overload (by phlebotomy) can be beneficial	10216143; 10802645; 12150153; 12130528; 19549277; 20542038; 21770687 
TG	11764	7038	Thyroid dyshormonogenesis 3	AR	Pediatric		Endocrine; Oncologic	Endocrine; Oncologic		Medical  treatment of hypothyroidism (eg, with T4) can be effective ; Thyroid neoplasms have also been reported, and surveillance may be beneficial to allow early treatment	2584351; 1752952; 14657345; 14557492; 14764776; 16187918; 16403815; 16720658; 16477365; 17244789
TGFB1	11766	7040	Camurati-Engelmann disease	AD	Pediatric	Allelic with Corneal dystrophy, Groenouw type I  (AD)	Hematologic; Musculoskeletal; Ophthalmologic	Musculoskeletal		Medical management (eg, corticosteroids and/or losartan) may be beneficial to help with many manifestations, including pain, gait disturbances, anemia, hepatosplenomegaly, and exercise intolerance	5503688; 4461085; 7298693; 9054935; 11062463; 10973241; 11810278; 21462384; 12493741; 15326622; 15894597; 20301335
TGFB2	11768	7042	Loeys-Dietz syndrome, type 4	AD	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal	Cardiovascular	Though manifestations may occur primarily in adults, surveillance in the pediatric period may be indicated	Individuals may manifest with cardiovascular anomalies, including thoracic aortic aneurysm as well as cardiac valvular anomalies, and awareness may allow early diagnosis and preventive measures and medical management in order to decrease morbidity and mortality	20301312; 22772371; 22772368
TGFB3	11769	7043	Arrhythmogenic right ventricular dysplasia 1; Reinhoff syndrome	AD	Pediatric		Cardiovascular; Craniofacial; Musculoskeletal	Cardiovascular		Individuals with Arrhythmogenic right ventricular dysplasia may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation; Individuals with Reinhoff syndrome have been described with cardiovascular anomalies including structural abnormalities as well as arrhythmia, and awareness may allow early management	1572740; 12529708; 15639475; 19362677; 20301310; 23824657; 24798638
TGFBI	11771	7045	Corneal dystrophy, lattice type I; Corneal dystrophy, lattice type IIIA; Corneal dystrophy of Bowman layer, type I; Corneal dystrophy, Avellino type; Corneal dystrophy, Reis-Bucklers type; Corneal dystrophy, Thiel-Behnke type; Corneal dystrophy, Groenouw type I; Corneal dystrophy, epithelial basement membrane 	AD	N/A	N/A	Ophthalmologic	General		It has been reported that in affected individuals with CDA, LASIK can increase the deposition of visually significant corneal opacities; Corneal epithelial debridement and fibronectin eye drops has been described  as potentially delaying the need for keratoplasty or phototherapeutic keratoplasty; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9054935; 9780098; 9727509; 9497262; 10442892; 11867580; 11923233; 15531312; 15019320; 15885785; 15111592; 15790870; 16652336; 16606891; 22080335; 22155582; 22194646; 22355247; 22575726 
TGFBR1	11772	7046	Loeys-Dietz syndrome, type 1A; Loeys-Dietz syndrome, type 2A	AD	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Obstetric	Cardiovascular; Obstetric		Medical management to decrease risk of vascular events is warranted, including avoidance of certain types of activities such as contact sports; Specific surveillance for surgical considerations related to issues such as aneurysms and cervical spine instability, other issues include subacute bacterial endocarditis prophylaxis with dental work; Precautions during pregnancy may be warranted due to the potential of complications including uterine rupture	5173258; 3565476; 15731757; 16928994; 20301312; 19542084; 21358634 
TGFBR2	11773	7048	Loeys-Dietz syndrome, type 2B; Loeys-Dietz syndrome, type 1B	AD	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Obstetric	Cardiovascular; Obstetric	An increased risk of colorectal cancer has been reported	Medical management to decrease risk of vascular events is warranted, including avoidance of certain types of activities such as contact sports; Specific surveillance for surgical considerations related to issues such as aneurysms and cervical spine instability, other issues include subacute bacterial endocarditis prophylaxis with dental work; Precautions during pregnancy may be warranted due to the potential of complications including uterine rupture	15235604; 16027248; 15731757; 16928994; 16251899; 19006214; 19542084; 19996017
TGIF1	11776	7050	Holoprosencephaly 4	AD	N/A	N/A	Craniofacial; Endocrine; Neurologic	General	Individuals with holoprosencephaly  may demonstrate endocrine anomalies, including diabetes insipidus 	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10835638; 16199538; 20104608; 22125506; 21940735
TGM1	11777	7051	Ichthyosis, congenital, autosomal recessive 1	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7977373; 7824952; 7773290; 9326318; 9545389; 12542526; 18948357; 19486042; 19556108; 19863506; 20064174; 20301593; 22435431 
TGM5	11781	9333	Peeling skin syndrome 2	AR	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16380904
TGM6	16255	343641	Spinocerebellar ataxia 35	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21106500; 22554020
TH	11782	7054	Segawa syndrome, autosomal recessive	AR	Pediatric		Biochemical; Neurologic	Biochemical		AR disease can have infantile onset, and treatment (eg, with L-dopa alone or combined with other medications), can be effective, though not has not been reported to be universally so	7814018; 8817341; 9732974; 10407773; 10585338; 11196107; 16049992; 17696123; 10753262; 11246459; 11241071; 11134401; 11921123; 12891655; 14705130; 15505183; 18058633; 19282209; 20056467; 20301610; 21937992; 21940685; 22264700; 22691284; 22815559; 23389938
THAP1	20856	55145	Dystonia 6, torsion	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9382482; 17702011; 19345147; 19345148; 19182804; 20211909; 20083799; 21520283; 21793105; 21839475; 21847143; 21949105; 22377579 
THBD	11784	7056	Thrombophilia due to thrombomodulin defect; Hemolytic uremic syndrome, atypical, susceptibility to, 6	AD	Pediatric (Hemolytic uremic syndrome, atypical, susceptibility to, 6); Adult (Thrombophilia due to thrombomodulin defect)		Hematologic; Renal	Hematologic; Pharmacogenomic; Renal	The evidence for the causality of the reported variants as relates to thrombophilia is unclear	In Thrombophilia due to thrombomodulin defect, surveillance, preventive measures, and treatment of thrombophilia may reduce morbidity; In Hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications)	7811989; 9843165; 10460600; 11552992; 12139752; 11986219; 19625716; 20301541; 20595690; 22036808
THPO	11795	7066	Thrombocythemia 1	AD	Pediatric		Hematologic; Oncologic	Hematologic; Oncologic		Individuals may have hemorrhagic or thrombotic tendencies, and preventive measures and prompt treatment may be beneficial; Surveillance for and early treatment of oncologic complications may also be beneficial	8167182; 7772529; 9425899; 10583217; 18367486; 22453305 
THRA	11796	7067	Hypothyroidism, congenital, nongoitrous, 6	AD	Pediatric		Endocrine	Endocrine		Thyroid replacement therapy has been reported as beneficial in some described individuals	22168587
THRB	11799	7068	Thyroid hormone resistance, general; Thyroid hormone resistance, selective pituitary 	AD/AR	Pediatric		Endocrine	Endocrine		In Thyroid hormone resistance, general, unhelpful, potentially invasive treatment regimens that may involve adverse effects may be avoided with efficient (genetic) diagnosis, and medical treatment (eg, with types of triiodothyroacetic acid) may be beneficial related to biological parameters as well as sequelae affecting multiple systems, such as the cardiovascular and neurologic systems; In Thyroid hormone resistance, selective pituitary, affected individuals may more frequently benefit from efforts to lower serum thyroid hormone concentration	4163616; 1159077; 6792914; 6287848; 3571851; 2510172; 2153155; 1991834; 1653889; 8381821; 8450877; 1400869; 8384535; 8496318; 8040303; 15913586; 17596672; 19268523; 19378427; 20020587; 22319036; 22696245; 22947347; 23134553; 23633200
TIA1	11802	7072	Welander distal myopathy	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23348830
TICAM1	18348	148022	Herpes simplex encephalitis, susceptibility to, 4	AD/AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may be susceptible to severe herpes simplex virus infections (eg, herpes encephalitis), and awareness may allow early diagnosis and treatment (eg, with acyclovir, which has been reported as effective reported individuals), potentially decreasing morbidity and mortality	22105173
TIMM8A	11817	1678	Opticoacoustic nerve atrophy with dementia; Jensen syndrome; Mohr-Tranebjaerg syndrome 	XL	Pediatric		Audiologic/Otolaryngologic; Musculoskeletal; Neurologic; Ophthalmologic	Audiologic/Otolaryngologic; Pharmacogenomic	Deafness may be postlingual in many individuals with certain TIMM8A-related conditions	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Aminoglycosides should be avoided	5649; 7643352; 8841189; 10878669; 11803487; 11405816; 18952432 
TIMP3	11822	7078	Sorsby fundus dystrophy	AD	N/A	N/A	Ophthalmologic	General	Vitamin A administration in early disease stages may postively affect manifestations such as night blindness, but long term efficacy is unclear; Antioangiogenic agents have been suggested as possibly beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18111349; 7148944; 7894485; 7550309; 8981947; 18501328 
TINF2	11824	26277	Dyskeratosis congenita, autosomal dominant 3; Revesz syndrome	AD	Pediatric		Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Pulmonary	Hematologic; Oncologic; Pulmonary		Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; Lung transplant may be indicated in individuals with advanced lung diease; HSCT may be indicated due to manifestations including leukemia and bone marrow failure (which may also be treated with androgen therapy), but the long-term efficacy may not be optimal	1404302; 18252230; 18669893; 20301779; 21199492
TJP2	11828	9414	Hypercholanemia, familial; Cholestasis, progressive familial intrahepatic 4	AR	Pediatric	Allelic with Deafness, autosomal dominant 51 (AD), which has been reported as due to genomic duplications	Audiologic/Otolaryngologic; Gastrointestinal	Gastrointestinal	Deafness, autosomal dominant 51 has been reported as due to genomic duplications, though evidence for causation of other variants appears to be unclear	In Hypercholanemia, Individuals may present with findings such as fat malabsorption, with consequent failure to thrive, coagulopathy, and rickets, and typically respond to medical treatment (eg, with ursodeoxycholic acid); In Familial intrahepatic cholestasis, medical treatment (eg, with ursodeoxycholine) may be beneficial, though liver transplantation has been described as necessary in some individuals; Medications (eg, OCPs) may lead to adverse reactions; In pregnancy, the condition can cause severe sequelae (including death) in the fetus, as well as adverse maternal health outcomes, and precautions, including early delivery, may be beneficial	12704386; 20602916; 24614073
TK2	11831	7084	Mitochondrial DNA depletion syndrome 2 	AR	N/A	N/A	Biochemical; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1734306; 11687801; 12391347; 18819985; 19125351; 19736010; 19815440; 20421844; 21937588; 22345218
TLL1	11843	7092	Atrial septal defect 6	AD	Pediatric		Cardiovascular	Cardiovascular	The condition can include arrhthymias as well as frank congenital cardiac malformations	In addition to managing congenital cardiac malformations, surveillance for (eg, including electrocardiogram) and treatment of accompanying arrhythmias may be effective	18830233
TLR3	11849	7098	Herpes simplex encephalitis, susceptibility to, 2	AD/AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may be susceptible to HSV (though not other) infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	17872438; 21911422 
TMC1	16513	117531	Deafness, autosomal recessive 7	AR	Pediatric	Allelic with Deafness, autosomal dominant 36 (AD)	Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	11850618; 17250663; 18616530; 23226338 
TMC6	18021	11322	Epidermodysplasia verruciformis	AR	Pediatric		Oncologic	Oncologic		Individuals are at high-risk of developing skin cancers, and surveillance may be beneficial to allow early detection and treatment	10084299; 10844558; 12426567
TMC8	20474	147138	Epidermodysplasia verruciformis	AR	Pediatric		Oncologic	Oncologic		Individuals are at high-risk of developing skin cancers, and surveillance may be beneficial to allow early detection and treatment	10084299; 10844558; 12426567
TMCO1	18188	54499	Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome	AR	Pediatric	 	Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Renal	Renal	The condition can involve multiple congenital anomalies	Individuals have been described with renal anomalies and/or vesicoureteral reflux, and surveillance and management may be helpful to preserve renal function	17351359; 20018682; 23320496; 24194475
TMEM126A	25382	84233	Optic atrophy 7	AR	N/A	N/A	Audiologic/Otolaryngologic; Cardiovascular; Neurologic; Ophthalmologic	General	One patient has been described as presenting with moderate hypertrophic cardiomyopathy; A heterozygote has been described as manifesting with transient loss of vision following exercise (Uhthoff's sign of optic neuropathy)	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19327736; 20301500; 20405026; 22815638
TMEM127	26038	55654	Pheochromocytoma	AD	Adult		Oncologic	Oncologic	Although adults have been reported, surveillance in the pediatric period may nevertheless be warranted	Surveillance and awareness of cancer risk may allow early diagnosis and treatment of neoplasms, which may reduce morbidity and mortality	20154675; 22419703; 23666964
TMEM138	26944	51524	Joubert syndrome 16	AR	N/A	N/A	Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial;	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22282472; 20301500 
TMEM165	30760	55858	Congenital disorder of glycosylation, type IIk	AR	N/A	N/A	Biochemical; Craniofacial; Dental; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic	General	Hepatic-metabolized agents should be avoided	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	22683087; 23430531
TMEM173	27962	340061	STING-associated vasculopathy, infantile-onsent (SAVI)	AD	N/A	N/A	Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Hematologic; Pulmonary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	25029335
TMEM216	25018	51259	Joubert syndrome 2; Meckel syndrome, type 2	AR	N/A	N/A	Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Conditions may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial;	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20036350; 20512146
TMEM231	37234	79583	Joubert syndrome 20; Meckel syndrome 11	AR	N/A	N/A	Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Conditions may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial;	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23012439; 23349226 
TMEM237	14432	65062	Joubert syndrome 14	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17603801; 20301500; 22152675
TMEM240	25186	339453	Spinocerebellar ataxia 21	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11160961; 25070513
TMEM38B	25535	55151	Osteogenesis imperfecta, type XIV	AR	N/A	N/A	Musculoskeletal	General	The use of bisphosphonates has been described in osteogenesis imperfecta, but it is unclear if an early (genomic) diagnosis would be advantageous	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23316006
TMEM43	28472	79188	Arrhythmogenic right ventricular dysplasia 5; Emery-Dreifuss muscular dystrophy 7	AD	Pediatric		Cardiovascular; Musculoskeletal	Cardiovascular		Individuals may manifest with arrhythmias (which have been reported in multiple individuals with EDMD 7), syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation 	18313022; 20301310; 21391237
TMEM5	13530	10329	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10	AR	N/A	N/A	Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	General	The condition involves multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23217329
TMEM67	28396	91147	Nephronophthisis 11; Meckel syndrome 3; Joubert syndrome 6; COACH syndrome	AR	N/A	N/A	Gastrointestinal; Neurologic; Musculoskeletal; Renal; Ophthalmologic	General	The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Variants may modify severity of BBS and related disorders due to mutations in other BBS-associated genes	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4688793; 17160906; 18327255; 19058225; 19508969; 19574260; 20232449; 20607301; 21633164; 21068128 
TMEM70	26050	54968	Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2	AR	N/A	N/A	Biochemical; Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18953340; 21147908; 24485043
TMEM98	24529	26022	Nanophthalmos 4	AD	N/A	N/A	Ophthalmologic	Ophthalmologic		As the condition can include glaucoma, surveillance can allow early interventions that may potentially be beneficial related to preservation of visual status	24852644
TMIE	30800	259236	Deafness, autosomal recessive 6	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	12145746; 19438934
TMLHE	18308	55217	Epsilon-trimethyllysine hydroxylase deficiency	AD	N/A	N/A	Biochemical	General	The condition may be associated with autism	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21865298; 22566635
TMPO	11875	7112	Cardiomyopathy, dilated, 1T	AD	Pediatric		Cardiovascular	Cardiovascular	The onset of symptoms has been described in adults, but surveillance and medical management may be beneficial prior to adulthood	Preventive measures, surveillance (eg, including echocardiography/electrocardiography),  and medical management may be helpful to help decrease morbidity	16247757
TMPRSS15	9490	5651	Enterokinase deficiency	AR	Pediatric		Gastrointestinal	Gastrointestinal		The condition tends to self-resolve, but early in life, pancreatic enzyme replacement or hydrolyzed  formula can be beneficial	4180366; 4322674; 1147667; 943355; 6347801; 11719902
TMPRSS3	11877	64699	Deafness, autosomal recessive 10; Deafness, autosomal recessive 8	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	11137999; 11907649; 16021470; 23226338 
TMPRSS6	16517	164656	Iron-refractory iron deficiency anemia	AR	Pediatric		Hematologic	Hematologic	Variants may also affect hemoglobin levels	The condition can involve anemia, which can be severe, and while oral iron therapy (as well as treatment with erythropoetin) alone may not be effective in all individuals (though some individuals have been reported who have been responsive to low-dose oral iron therapy), combination therapy with oral iron and ascorbic acid has been reported as beneficial, and parenteral iron therapy has been reported as partially effective in some individuals	7229750; 3354554; 8602626; 10524456; 11517621; 18408718; 18596229; 19786206; 21618415; 21643693; 21783390; 22169218; 23180434; 23319530  
TNC	5318	3371	Deafness, autosomal dominant 56	AD	N/A	N/A	Audiologic/Otolaryngologic	General	Deafness has been described as postlingual	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23936043
TNFRSF10B	11905	8795	Squamous cell carcinoma, head and neck	AD	Pediatric		Oncologic	Oncologic		Surveillance and early diagnosis could potentially be beneficial to allow prompt management of detected neoplasms	9721851
TNFRSF11A	11908	8792	Polyostotic osteolytic dysplasia, hereditary expansile; Paget disease of bone; Osteopetrosis, autosomal recessive 7	AD/AR	Pediatric (Polyostotic osteolytic dysplasia, hereditary expansile/Osteopetrosis, autosomal recessive 7); Adult (Paget disease of bone)		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Dental; Endocrine; Musculoskeletal; Oncologic	Allergy/Immunology/Infectious; Endocrine; Musculoskeletal; Oncologic 		In Osteopetrosis, autosomal recessive 7, individuals can present with hypocalcemic seizures, which are responsive to treatment; Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; In Polyostotic osteolytic dysplasia, hereditary expansile, HSCT has been reported as effective, including when performed in late infancy; For Paget disease of bone, medical management (eg, inhibitors of osteoclastic bone resorption) can be beneficial -  bisphosphonates are current first line of treatment, and awareness of the risk of related oncologic processes (eg, osteosarcoma) may be beneficial to allow early diagnosis and treatment	3346299; 2530018; 9626117; 10615125; 11123042; 18606301; 18328984; 18672105; 19940926; 22271396 
TNFRSF11B	11909	4982	Paget disease, juvenile	AR	Pediatric		Dental; Endocrine; Musculoskeletal	Endocrine; Musculoskeletal		Individuals may present with manifestations including osteopenia, fractures, and progressive skeletal deformity, and benefits to medical treatment (eg, with disodium etidronate, bisphosphonates, osteoprotegerin) have been reported	13368018; 14123485; 5675396;  1593590; 8053403; 8770706; 12189164; 12124406; 14672344; 16135836; 17352649 
TNFRSF13B	18153	23495	Immunoglobulin A deficiency 2; Common variable immunodeficiency 2	AD/AR	Pediatric		Allergy/Immunology/Infectious; Oncologic	Allergy/Immunology/Infectious; Oncologic		In CVID2, prophylaxis and early and aggressive treatment of infections may be beneficial; In most cases, IGA deficiency 2 is not associated with any illness, though some may have increased infections, malignancies, and autoimmune disorders	11720003; 16007086; 16049503; 16007087; 18981294
TNFRSF13C	17755	115650	Immunodeficiency, common variable 4	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious	Although the condition has only been described in adults, interventions may be indicated in the pediatric period	Individuals may be susceptible to a number of infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	19666484
TNFRSF1A	11916	7132	Periodic fever, familial (TNF receptor-associated periodic syndrome)	AD	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Neurologic	Allergy/Immunology/Infectious		Individuals may manifest with sequelae such as periodic fever, pain, and rash, and medical treatment with TNF inhibitors  (eg, etanercept) has been reported as effective in many individuals	1402641; 9585614; 9529351; 10199409; 10412980; 11115159; 11175303; 12584543; 17360963; 19381634; 21153346; 21225694; 21378401; 21869706; 22675839; 22281876 
TNFRSF4	11918	7293	Immunodeficiency 16	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may be susceptible to severe infections, as well as related oncologic sequelae (eg, Kaposi sarcoma), and early and aggressive treatment of infections and related sequelae may be beneficial	20156905; 23897980
TNFSF11	11926	8600	Osteopetrosis, autosomal recessive 2	AR	Pediatric		Audiologic/Otolaryngologic; Dental; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	Hematologic; Musculoskeletal		Individuals may present early in life with audiologic, neurologic, and ophthalmologic manifestations including hydrocephalus and visual impairment,  as well as other findings including hepatosplenomegaly and fractures with poor bone remodeling, and awareness of complications may allow surveillance and prompt treatment; HSCT has been reported as beneficial	17632511
TNNC1	11943	7134	Cardiomyopathy, familial hypertrophic 13; Cardiomyopathy, dilated, 1Z	AD	Pediatric		Cardiovascular	Cardiovascular		Preventive measures, surveillance (eg, including echocardiography and electrocardiography),  and medical management may be helpful to help decrease morbidity; Cardiac transplantation has been reported	11385718; 15542288; 18572189 
TNNI2	11946	7136	Arthrogryposis multiplex congenita, distal, type 2B	AD	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12592607; 16802141
TNNI3	11947	7137	Cardiomyopathy, familial hypertrophic 7; Cardiomyopathy, dilated 1FF; Cardiomyopathy, dilated, 2A; Cardiomyopathy, familial restrictive	AD/AR	Pediatric		Cardiovascular	Cardiovascular		Preventive measures, surveillance (eg, including echocardiography and electrocardiography),  and medical management may be helpful to  decrease morbidity; Cardiac transplantation has been reported	3594932; 9241277; 9753711; 12531876; 15070570; 16267253; 19590045; 20569525; 21846512; 22301726; 22455086; 22876777; 23349452; 23396983; 23906401
TNNI3K	19661	51086	Cardiac conduction disease with or without dilated cardiomyopathy	AD	Pediatric		Cardiovascular	Cardiovascular		Individuals have been described with arrhythmia and cardiomyopathy, and awareness may allow early medical/surgical management (eg, medical management and catheter-based ablation of cardiac foci has been described as beneficial)	24925317
TNNT1	11948	7138	Nemaline myopathy 5	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10952871
TNNT2	11949	7139	Cardiomyopathy, familial restrictive, 3; Cardiomyopathy, dilated, 1D; Left ventricular noncompaction 6; Cardiomyopathy, familial hypertrophic, 2 	AD	Pediatric		Cardiovascular	Cardiovascular		Preventive measures, surveillance (eg, including echocardiography and electrocardiography),  and medical management may be helpful to help decrease morbidity	7981753; 8205619; 7898523; 9714088; 11106718; 11684629; 15542288; 16651346; 18506004; 18651846; 21483645; 21846512; 22144547; 22292720
TNNT3	11950	7140	Arthyrgryposis, distal, type 2B	AD	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12865991
TNPO3	17103	23534	Muscular dystrophy, limb-girdle, type 1F	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11222786; 23543484; 23667635
TNXB	11976	7148	Vesicoureteral reflux 8; Ehlers-Danlos syndrome, autosomal recessive, due to tenascin X deficiency	AD/AR	Pediatric		Cardiovascular; Dermatologic; Gastrointestinal; Musculoskeletal; Renal	Cardiovascular; Gastrointestinal; Renal	Variants may also be involved in vesicoureteral reflux	In Vesicoureteral reflux, monitoring and intervention related to renal sequelae may be beneficial in terms of helping to preserve renal function; In Ehlers-Danlos syndrome, reported features include aortic dilatation (which may not have a high risk of progression), severe diverticular intestinal disease with ruptured diverticula, pancolonic diverticulitis, and rectal prolapse, mitral valve prolapse requiring valve replacement, and obstructive airway disease, though it is not clear if these are all related to TNXB or to other genetic anomalies; Surveillance related to cardiovascular anomalies may be beneficial	9288108; 11642233; 12180144; 12865992; 15793839; 15733269; 19921645; 19557868; 20301456; 21959861; 23284009; 23620400; 23768946
TOPORS	21653	10210	Retitinis pigmentosa 31	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16189705; 17924349; 18509552; 19183411 
TOR1A	3098	1861	Dystonia 1, torsion	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9288096; 10541594; 10435508; 11523564; 12391355; 11973627; 12481989; 12402271; 12975293; 15326234; 16275837; 17503336; 18519876; 19955557; 20925076; 21515903; 22132914 
TP53	11998	7157	Li-Fraumeni syndrome; Choroid plexus papilloma; Ependymoma, intracranial; Osteogenic sarcoma; Breast cancer, familial; Hepatoblastoma; Non-Hodgkin lymphoma; Adrenocortical carcinoma; Colorectal cancer	AD	Pediatric		Oncologic	Oncologic	Variants may also be involved in susceptibility to a number of types of neoplasms (eg, Basal cell carcinoma, susceptibility to, Glioma, susceptibility to)	Though the optimal course is unclear, surveillance (including breast cancer and colorectal cancer screening starting no later than age 25) and awareness of the increased risk of malignancy could potentially be beneficial in order to allow early diagnosis and treatment; Mastectomy is preferred to lumpectomy in individuals with breast cancer, and may be a prophylactic option; Radiation therapy should be avoided due to the risk of radiation-induced malignancies	6016796; 3409256; 1978757; 1679237; 1591732; 1349175; 1565144; 1565143; 8118819; 8718514; 7887414; 9242456; 10612830; 11332399; 11498785; 11600572; 11219776; 11481490; 12085209; 12610779; 12524418; 12619118; 14583457; 12619118; 15381368; 15695383; 15977174; 15741269; 18762572; 19171829; 19556618; 19652052; 20301488; 21056402; 21601526; 21837677; 21946351; 21990040; 22170717; 22551548; 22672556; 22878818; 22939227; 23015295; 23175693; 23355100; 23409989; 23667851; 23894400
TP63	15979	8626	Split-hand/foot malformation 4; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3; Limb-mammary syndrome; Rapp-Hodgkin syndrome; Orofacial cleft 8; ADULT syndrome; Ankyloblepharon-ectodermal defects-cleft lip/palate	AD	N/A	N/A	Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5713637; 946410; 3366140; 9443880; 10535733; 9973291; 10886756; 10839977; 11528512; 11159940; 11462173; 11929852; 12838557; 12939657; 14684701; 12766194; 15200513; 16688749; 16740912; 17041931; 16724007; 17609671; 17431922; 18627043; 19239083; 18603493; 19697430; 19353643; 19676059; 19530185; 21204238; 21990121; 22065540; 22065614; 22069181; 22430731; 22574117; 22607287; 22740388 
TPCN2	20820	219931	Skin/hair/eye pigmentation, variation in, 10	AD	N/A	N/A	Dermatologic	General	Variants may be involved in sun sensitivity	The condition may not be clinically relevant	18488028
TPI1	12009	7167	Triosephosphate isomerase deficiency	AR	Pediatric		Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Neurologic	Allergy/Immunology/Infectious; Hematologic		Surveillance and early treatment for complications affecting other organ systems, such as hematologic complications and cardiomyopathy can be beneficial (RBC transfusions have been described as beneficial); Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	2569601; 2876430; 3619568; 14242501; 1959537;  4065896; 6946452; 8244340; 8503454; 8639817; 9294216; 9338582; 10209987; 10782327; 10910933; 10916682; 11196750; 14984912; 17424909; 17879449; 19786097; 20374271; 21215915; 24056040
TPK1	17358	27010	Thiamine metabolism dysfunction syndrome 5	AR	Pediatric		Biochemical; Neurologic	Biochemical		In some individuals, thiamine supplementation appears to have beneficial effect (related compounds may be beneficial as well)	22152682
TPM1	12010	7168	Cardiomyopathy, dilated, 1Y; Cardiomyopathy, familial hypertrophic, 3	AD	Pediatric		Cardiovascular	Cardiovascular		Surveillance (eg, with echocardiography/electrocardiography), preventive measures and medical management, including ICD treatment, may be helpful to help decrease morbidity	8205619; 7898523; 11136687; 11273725; 21823217 
TPM2	12011	7169	Nemaline myopathy 4; CAP myopathy; Arthrogryposis multiplex congenita, distal, type 1; Arthrogryposis, distal, type 2B 	AD	N/A	N/A	Cardiovascular; Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11738357; 12592607; 17434307; 17846275; 19047562; 19345583; 22084935; 22798622; 22832343 
TPM3	12012	7170	Nemaline myopathy 1, autosomal dominant; CAP myopathy; Myopathy, congenital, with fiber-type disproportion	AD	N/A	N/A	Craniofacial; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18300303
TPMT	12014	7172	Thiopurine S-methyltransferase deficiency	AR	Pediatric		Biochemical	Pharmacogenomic		Dose adjustment/selection of specific medications (eg, azathioprine, cisplatin, mercaptopurine, s-adenoslymethionine, thioguanine) may be indicated in order to avoid severe toxicity 	2758725; 1960624; 7862671; 8644731; 9177237; 11304783; 15228163; 16220112; 19898482 
TPO	12015	7173	Thyroid dyshormonogenesis 2A	AR	Pediatric		Endocrine; Oncologic	Endocrine; Oncologic		Medical  treatment of hypothyroidism (eg, with T4) can be effective; Thyroid neoplasms have also been reported, and surveillance may be beneficial	1401057; 8027236; 9814507; 10084596
TPP1	2073	1200	Ceroid lipofuscinosis, neuronal, 2; Spinocerebellar ataxia, autosomal recessive 7	AR	N/A	N/A	Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5634370; 5795346; 4116925; 3146310; 7668319; 9295267; 9788728; 10330339; 12376936; 15965709; 17959406; 18684116; 20820830; 21990111; 22612257; 23266810; 23418007
TPRN	26894	286262	Deafness, autosomal recessive 79	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	19603065; 20170898; 23340767
TRAC	12029	28755	T-cell receptor-alpha/beta deficiency	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Prophylactic measures, surveillance, and early and aggressive treatment of infections may be beneficial; BMT has been described	21206088
TRAF3	12033	7187	Herpes simplex encephalitis, susceptibility to, 3	AD	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may be susceptible to severe herpes simplex virus infections (eg, herpes encephalitis has been described), and awareness may allow early diagnosis and treatment (eg, with acyclovir, which has been reported as effective in the reported individual), potentially decreasing morbidity and mortality	20832341
TRAF3IP2	1343	10758	Candidiasis, familial 8	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals have been reported as having recurrent candidal (and other) infections, and surveillance, prophylaxis, and early treatment may be beneficial	24120361
TRAP1	16264	10131	Congenital abnormalities of the kidney and urinary tract; VACTERL association	AR	Pediatric		Cardiovascular; Gastrointestinal; Genitourinary; Musculoskeletal; Renal	Renal	The conditions may involve multiple congenital anomalies	Monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function	24152966
TRAPPC11	25751	60684	Limb-girdle muscular dystrophy, type 2S	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23830518
TRAPPC2	23068	6399	Spondyloepiphyseal dysplasia tarda, X-linked	XL	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10431248; 14755465; 15316971; 19002213; 19417549; 19766614; 20301324; 22563562; 23656395
TRAPPC9	30832	83696	Mental retardation, autosomal recessive 13	AR	N/A	N/A	Craniofacial; Endocrine; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17120046; 20004765; 20004763; 20004764; 21629298; 22549410; 22989526 
TRDN	12261	10345	Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness	AR	Pediatric		Cardiovascular; Neurologic	Cardiovascular		Individuals may present with severe cardiac manifestations, including arrhythmias, syncope, and sudden death, and surveillance, preventive measures (eg, including avoidance of dangerous or excacerbating factors), and treatment (eg, including interventions such as medical treatment with beta-blockers or ICD placement) may allow early and beneficial management, which may decrease morbidity and mortality	22422768
TREM2	17761	54209	Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy; Nasu-Hakola disease; Early-onset dementia without bone cysts	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12080485; 15883308; 1854636; 21834902; 23318515 
TREX1	12269	11277	Chilblain lupus 1; Vasculopathy, retinal, with cerebral leukodystrophy; Aicardi-Goutieres syndrome 1	AD/AR	N/A	N/A	Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6712192; 3731164; 3174024; 1821204; 8592332; 9371916; 10449133; 15807828; 16845398; 16960810; 17440703; 17660818; 17846997; 17660820; 20301648; 20799324; 21808053; 22356656; 22829693 
TRHR	12299	7201	Thyrotropin-releasing hormone resistance, generalized	AR	Pediatric		Endocrine	Endocrine		Medical treatment of hypothroidism can be effective	9141550; 19213692
TRIM2	15974	23321	Charcot-Marie-Tooth disease, axonal, type 2R	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23562820
TRIM32	16380	22954	Muscular dystrophy, limb-girdle, type 2H; Bardet-Biedl syndrome 11 	AR	N/A	N/A	Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition frequently involves multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4269389; 10399877; 11822024; 15886712; 15580560; 16243356; 15786463; 16606853; 17994549; 19492423; 20301537; 20177705; 21775502; 22981120
TRIM37	7523	4591	Mulibrey nanism	AR	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic	Cardiovascular; Oncologic	The condition may involve multiple malformations	Surveillance and early detection of and treatment for malignancy (Wilms tumors,  as well a number of other cancer types have been reported) may decrease morbidity and mortality; Awareness of cardiovascular anomalies (including structural anomalies, as well as pericardial constriction and congestive heart failure) may be beneficial in order to allow early diagnosis and treatment	4124529; 135512; 8335020; 10888877; 12754710; 14757854; 15108285; 15590968; 16306379; 17100991; 16310976; 17551331; 19329943; 19334051; 21865362; 23385855
TRIOBP	17009	11078	Deafness, autosomal recessive 28	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	16385457; 16385458; 23226338 
TRIP11	12305	9321	Achondrogenesis, type IA	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4885523; 7460382; 3275766; 20089971
TRMT10A	28403	93587	Microcephaly, short stature, and impaired glucose metabolism	AR	Pediatric		Craniofacial; Endocrine; Musculoskeletal; Neurologic	Endocrine		Awareness of the risk of diabetes may allow prompt recognition and treatment	24204302; 25053765
TRMU	25481	55687	Liver failure, infantile, transient; Reversible infantile respiratory chain deficiency	AR	N/A	N/A	Biochemical; Gastrointestinal	General	In Liver failure, infantile, transient, with supportive care, patients surviving the initial acute episode can recover and demonstrate typical development; Genetic diagnosis may be beneficial in order to determine therapy	 Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12408186; 11230176; 19732863; 21931168; 21931168 
TRNH	7487	4564	Deafness, nonsyndromic, sensorineural	Maternal	Pediatric	Allelic with Myoclonic epilepsy with ragged red fibers (Maternal); Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (Maternal)	Audiologic/Otolaryngologic; Biochemical; Gastrointestinal; Musculoskeletal; Neurologic	Audiologic/Otolaryngologic	As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment, with highly variable age of onset, and for individuals with early-onset hearing impairment, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	14967777; 21931169
TRNI	7488	4565	Deafness, mitochondrial; Hypertension, hypercholesterolemia, and hypomagnesemia  (Maternal)	Maternal	Pediatric	Allelic with Cardiomyopathy, fatal (Maternal); Cardiomyopathy, familial hypertrophic (Maternal); Encephalopathy, familial progressive necrotizing (Maternal); Mitochondrial multisystemic disorder (Maternal)	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Endocrine; Musculoskeletal; Neurologic; Renal	Audiologic/Otolaryngologic; Renal	Individuals have been described with a wide range of cardiovascular manifestations, including fatal infantile forms, as well as familial hypertrophic cardiomyopathy; Cardiac transplant has been described	Treatment of electrolyte abnormalities, as well as blood pressure control, can be beneficial; For prelingual hearing loss, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Aminoglycosides should be avoided	11782991; 12767666; 15121771; 15498972; 1632786; 889580; 15121771; 15498972;  1978914; 22241583
TRNK	7489	4566	Parkinson disease, mitochondrial; Myoclonic epilepsy with ragged red fibers; Diabetes-deafness syndrome; Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes	Maternal	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment; Individuals with Parkinson disease have been reported as responding to therapies such as levodopa; The conditions can include features common to other mitochondrial disorders; As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2112427; 1463005; 8069654; 9571188; 17200493
TRNP	7494	4571	Myoclonic epilepsy with ragged red fibers	Maternal	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic	General	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment; As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19273760
TRNQ	7495	4572	Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes	Maternal	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic	General	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11171912
TRNS2	7498	4575	Myoclonic epilepsy with ragged red fibers; Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes; Retinitis pigmentosa-deafness syndrome	Maternal	N/A	N/A	Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	General	Mitochondrial mutations may involve a variety of sequelae, including hearing impairment; As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8364569; 9135384; 10090882; 16950817
TRNT	7499	4576	Mitochondrial myopathy, lethal	Maternal	N/A	N/A	Biochemical; Musculoskeletal; Neurologic	General	The pathogenicity of the reported variant is unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	2549452; 1645537; 1379415
TRNT1	17341	51095	Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Hematologic; Neurologic; Ophthalmologic; Renal	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Hematologic		Medical management (with immunoglobulin therapy) has been described as beneficial; Most patients have been described as requiring regular blood transfusions for treatment of anemia, as well as iron chelation; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; BMT has been described	25193871
TRPA1	497	8989	Episodic pain syndrome, familial	AD	N/A	N/A	Neurologic	General	Individuals have been described as suffering from episodes of severe pain that could, to some extent, be predicted and ameliorated, but it is unclear if genetic diagnosis would be additionally advantageous (in addition to clinical diagnosis)	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20547126
TRPC6	12338	7225	Focal segmental glomerulosclerosis 2	AD	N/A	N/A	Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10200986; 15924139; 15879175; 21415313; 21511817; 21734084 
TRPM1	7146	4308	Night blindness, congenital stationary, type 1C	AR	N/A	N/A	Ophthalmologic	General	Dermatologic findings (eg, dry skin; a condition resembling epidermolysis bullosa simplex) have been described, but it is not clear if these are part of the core phenotype	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19896113; 19878917; 19896109; 20300565
TRPM4	17993	54795	Progressive familial heart block, type IB	AD	Pediatric		Cardiovascular	Cardiovascular		Preventive measures (eg, pacemakers and other medical measures) have been shown to be effective to control sequelae, which can include sudden death	897853; 619595; 4003252; 3750143; 3347879; 9023172; 19726882; 20562447; 21887725 
TRPM6	17995	140803	Hypomagnesemia 1, intestinal	AR	Pediatric		Gastrointestinal	Gastrointestinal		Individuals typically present in infancy with manifestations of electrolyte imbalances (hypomagnesemia and consequent hypocalcemia) , which may result in death or severe neurologic impairment  such that immediate  magnesium administration can be effective in the acute period, though individuals require chronic high-dose oral magnesium supplementation	12032568; 12032570
TRPS1	12340	7227	Trichorhinophalangeal syndrome, type I; Trichorhinophalangeal syndrome, type III	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5991804; 10615131; 11112658; 19419465; 19610100; 19758263; 20394624; 21740822; 22481165 
TRPV3	18084	162514	Olmsted syndrome	AD	N/A	N/A	Dermatologic	General	Infections and skin cancer have been described at arising at the site of skin lesions	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22405088
TRPV4	18083	59341	Spinal muscular atrophy, distal, congenital nonprogressive; Brachyolmia type 3; Metatropic dysplasia; Spondyloepiphyseal dysplasia, Maroteaux type; Scapuloperoneal spinal muscular atrophy; Hereditary motor and sensory neuropathy, type Iic; Spondylometaphyseal dysplasia, Kozlowski type; Parastremmatic dwarfism; Digital arthropathy-brachydactyly, familial 	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4992387; 4056805; 1520078; 8179305; 9781046; 10463355; 12884428; 14755468; 15668982; 17879966; 18348257; 18587396; 19232556; 20037588; 20425821; 21115951; 20577006; 20037587; 20037586; 20503319; 21336783; 21288981; 21964829; 21964574; 22065612; 22206013; 22419508; 22526352; 22617546; 22675077; 22791502; 22851605 
TRRAP	12347	8295	Schizophrenia	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23042115
TSC1	12362	7248	Tuberous sclerosis; Lymphangioleiomyomatosis	AD	Pediatric	Allelic with Focal cortical dysplasia of Taylor (AD)	Cardiovascular; Dental; Dermatologic; Neurologic; Oncologic; Ophthalmologic; Pulmonary; Renal	Cardiovascular; Neurologic; Oncologic; Pulmonary; Renal		Surveillance for and early treatment of tumors, as well as other manifestations affecting multiple organ systems (eg, renal anomalies, pulmonary manifestations, neurologic manifestations, and cardiac manifestations including arrhythmias) may reduce morbidity and mortality; Treatment with mTOR inhibitors may be beneficial related to neoplastic sequelae as well as related seizures; Lymphangiomyomatosis can occur as an isolated disorder or in association with TSC - the only effective therapy in late stage disease is transplant	14421523; 2823681; 3210031; 2706800; 8534286; 8592324; 8782048; 9132502; 9242607; 9863590; 9924605; 9579160; 11829138; 12112044; 14985384; 15257730; 15955990; 17003820; 17005952; 17304050; 18722871; 18032745; 19332694; 19419980; 21266383; 20301399; 21813552; 22189265; 22161988; 22490766; 23158522; 23743818; 23796861; 23845174; 23846400; 23851963; 23852707; 23909960
TSC2	12363	7249	Tuberous sclerosis 2; Lymphangioleiomyomatosis 	AD	Pediatric		Cardiovascular; Dental; Dermatologic; Neurologic; Oncologic; Ophthalmologic; Pulmonary; Renal	Cardiovascular; Neurologic; Oncologic; Pulmonary; Renal		Surveillance for and early treatment of tumors, as well as other manifestations affecting multiple organ systems (eg, renal anomalies, neurologic manifestations, pulmonary manifestations, and cardiac manifestations including arrhythmias) may reduce morbidity and mortality; Treatment with mTOR inhibitors may be beneficial related to neoplastic sequelae as well as related seizures; Lymphangiomyomatosis can occur as an isolated disorder or in association with TSC - the only effective therapy in late stage disease is transplant	14421523; 2823681; 3210031; 2706800; 1303246; 8162074; 8534286; 8824721; 8782048; 9302281; 9132502; 9463313; 9579160; 11829138; 14985384; 15955990; 17003820; 17005952; 17120248; 17304050; 18722871; 18032745; 19258298; 19332694; 19419980; 21266383; 21813552; 20301399; 22189265; 22490766; 23158522; 23733802; 23743818; 23757617; 23796861; 23845174; 23852707
TSEN2	28422	80746	Pontocerebellar hypoplasia type 2B	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18711368
TSEN34	15506	79042	Pontocerebellar hypoplasia type 2C	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18711368
TSEN54	27561	283989	Pontocerebellar hypoplasia, type 2A; Pontocerebellar hypoplasia type 4	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8480512; 16470708; 18711368; 20956791
TSFM	12367	10102	Combined oxidative phosphorylation deficiency 3	AR	N/A	N/A	Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17033963; 21119709; 22499341
TSHB	12372	7252	Hypothyroidism, congenital, nongoitrous, 4	AR	Pediatric		Endocrine	Endocrine		The untreated condition can result in severe neurological damage, and recognition can allow early medical treatment with thyroid hormone replacement can prevent such sequelae	2792087; 1971148; 8636437; 9589689; 11297590; 11549695; 12364478; 11788671; 15292359; 16804796 
TSHR	12373	7253	Hyperthyroidism, familial, gestational; Hyperthyroidism, nonautoimmune; Hypothyroidism, congenital, nongoitrous, 1	AD/AR	Pediatric		Endocrine	Endocrine	Variants may also be associated with a number of thyroid-related presentations	In Hyperthyroidism, familial, gestational, recognition and treatment of hyperthyroidism during pregnancy (eg, with propylthiouracil) can lead to positive gestational outcomes; In Hyperthyroidism (including in early-onset types), recognition can allow prompt treatment with medical or surgical ablation, as recurrent hyperthyroidism after subtotal thyroidectomy (necessitating repeat treatment), has been described; In conditions resulting in hypothyroidism, medical  treatment of hypothyroidism (with T4) can be effective	7920658; 7800007; 7528344; 8954020; 9185526; 9329388; 9100579; 9385128; 9854118; 10487707; 12050212; 20146656; 20718767; 21186955; 21283701; 21677043; 21714469; 22405933; 22763653; 22876533; 23154162; 23329763; 23412867; 23563316; 23698639
TSHZ1	10669	10194	Aural atresia, congenital	AD	Pediatric		Audiologic/Otolaryngologic; Craniofacial	Audiologic/Otolaryngologic	The condition may be recognizable from physical examination	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	22152683
TSPAN12	21641	23554	Exudative vitreoretinopathy 5; Retinal dysplasia and severe familial exudative vitreoretinopathy	AD/AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20159111; 20159112; 20301326;  21334594; 21552475; 22427576 
TSPAN7	11854	7102	Mental retardation, X-linked 58	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10449641; 10655063; 14735593
TSPEAR	1268	54084	Deafness, autosomal recessive 98	AR	Pediatric		Audiologic/Otolaryngologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	22678063
TSPYL1	12382	7259	Sudden infant death with dysgenesis of the testes syndrome; 46, XY disorder of sex development	AR	N/A	N/A	Genitourinary; Neurologic 	General		In Sudden infant death with dysgenesis of the testes syndrome, death has been described during inpatient cardiorespiratory monitoring; In 46, XY disorder of sexual development, individuals may have the potential for gonadal tumors; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15273283; 19463995 
TTBK2	19141	146057	Spinocerebellar ataxia 11	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18037885
TTC19	26006	54902	Mitochondrial complex III deficiency, nuclear type 2	AR	N/A	N/A	Biochemical; Neurologic; Musculoskeletal	General	Individuals may suffer acute episodes of metabolic crisis; Treatment with "Mitochondrial cocktail" type therapy may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21278747; 23532514; 24368687; 24397319
TTC21B	25660	79809	Nephronophthisis 12; Short-rib thoracic dysplasia 4 with or without polydactyly	AR	N/A	N/A	Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20301500; 21258341
TTC37	23639	9652	Trichohepatoenteric syndrome 1	AR	Pediatric		Allergy/Immunology/Infectious; Craniofacial;  Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal	Allergy/Immunology/Infectious; Gastrointestinal	The condition may be clinically recognizable, and prognosis may be poor in some individuals despite optimal therapy	Individuals may also have immunodeficiency, and may benefit from prophylaxis and early and aggressive treatment of infections; Intractable diarrhea in infancy may require total parenteral nutrition; Patients may require hepatic transplant	70733018021782; 9021008; 9481629; 14521564; 15069414; 17236206; 17318842; 20176027; 21120949
TTC7A	19750	57217	Intestinal atresia, multiple	AR	N/A	N/A	Allergy/Immunology/Infectious; Gastrointestinal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23423984
TTC8	20087	123016	Bardet-Biedl syndrome 8; Retinitis pigmentosa 51	AR	N/A	N/A	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Bardet-Biedl syndrome frequently involves multiple congenital anomalies and multisystemic manifestations	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14520415; 16308660; 20301537; 20451172
TTI2	26262	80185	Mental retardation, autosomal recessive 39	AR	N/A	N/A	Craniofacial; Dental; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21937992; 23956177
TTLL5	19963	23093	Cone-rod dystrophy 19	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24791901
TTN	12403	7273	Cardiomyopathy, familial hypertrophic 9; Cardiomyopathy, dilated, 1G	AD	Pediatric	Allelic with Hereditary myopathy with early respiratory failure (AD); Tibial muscular dystrophy (AD); Myopathy, early-onset, with fatal cardiomyopathy (AR); Muscular dystrophy, limb-girdle, type 2J (AR)	Cardiovascular; Musculoskeletal	Cardiovascular	Some allelic conditions have been reported as potentially including cardiovascular anomalies, but  it is unclear if molecular diagnosis was uniformly verified	Surveillance (including with echocardiography) may allow early detection and treatment, (including with interventions such as left ventricular assist device), and preventive measures may be additionally beneficial; Heart transplantation has been described	4855680; 126303; 196233; 6251174; 1619633; 1487757; 10053013; 10462489; 11788824; 12145747; 11846417; 12891679; 15802564; 17444505; 20627570; 22335739; 22577215; 22475360
TTPA	12404	7274	Ataxia with isolated vitamin E deficiency	AR	Pediatric		Gastrointestinal; Neurologic	Gastrointestinal		Preventive treatment with vitamin E administration can ameliorate signs and symptoms of disease; Untreated, individuals typically present with neurological manifestations, including progressive ataxia, and knowledge can allow early treatment (which involves chronic supplementation with high-dose oral vitamin E, with the goal of maintaining plasma vitamin E concentrations in the high-normal range)	4000224; 3361234; 7887897; 7719340; 8602747; 8972536; 463307; 10552255; 11554913; 12039660; 15300460; 20301419 
TTR	12405	7276	Amyloidosis, hereditary, transthyretin-related; Dystransthyretinemic hyperthyroxinemia	AD	Pediatric	Allelic with Carpal tunnel syndrome, familial (AD)	Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	Cardiovascular; Endocrine; Gastrointestinal; Neurologic		In Familial transthyretin amyloidosis, surveillance for cardiovascular sequelae (which can include arrhythmias), and earlier treatment (eg, pacemaker) can be beneficial, and liver transplantation may be beneficial especially early in the disease course; Therapies involving transthyretin stabilization or RNA interference may be beneficial, especially in early stages of disease; In Dystransthyretinemic hyperthyroxinemia, diagnosis may be important in order to avoid unecessary treatment (eg, thyroid ablation)	13320157; 7417777; 6801514; 3229002; 1979335; 7839813; 8309582; 8784093; 8579098; 9017939; 10523220; 10869060; 11261421; 11385707; 11940682; 14640030; 14986482; 15249622; 15820680; 16357452; 15725588; 17554795; 19075702; 17200500; 18022643; 20301373; 22094129; 22843282; 23193944; 23483184; 23834402; 23901247; 23931808; 23984729; 23984729; 23993291; 24000164; 24023270; 24053266
TUBA1A	20766	7846	Lissencephaly 3	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17218254; 17584854; 18728072; 18954413; 21403111; 22264709; 22633752; 22948023; 23317684; 23528852; 23361065
TUBA8	12410	51807	Polymicrogyria with optic nerve hypoplasia	AR	N/A	N/A	Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19896110
TUBB	20778	203068	Cortical dysplasia, complex, with other brain malformations 6	AD	N/A	N/A	Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23246003
TUBB1	16257	81027	Macrothrombocytopenia, autosomal dominant, TUBB1-related	AD	N/A	N/A	Hematologic	General		The clinical significance is unclear	15956286; 18849486
TUBB2A	12412	7280	Cortical dysplasia, complex, with other brain malformations 5	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24702957
TUBB2B	30829	347733	Polymicrogyria, asymmetric	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19465910; 22333901; 23361065; 23495813
TUBB3	20772	10381	Cortical dysplasia, complex, with other brain malformations 1; Fibrosis of extraocular muscles, congenital, 3A	AD/AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7724178; 10393037; 12073023; 20829227; 20074521
TUBB4A	20774	10382	Dystonia 4, torsion, autosomal dominant; Leukodystrophy, hypomyelinating, 6	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3156966; 23582646; 23595291; 24013879;  24526230; 24742798; 24850488; 25085639
TUBG1	12417	7283	Cortical dysplasia, complex, with other brain malformations 4	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23603762
TUBGCP6	18127	85378	Microcephaly and chorioretinopathy with or without mental retardation, autosomal recessive	AR	N/A	N/A	Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5936364; 22279524
TUFM	12420	7284	Combined oxidative phosphorylation deficiency 4	AR	N/A	N/A	Biochemical; Gastrointestinal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17160893
TULP1	12423	7287	Leber congenital amaurosis 15; Retinitis pigmentosa 14	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9462751; 9462750; 15024725; 15557452; 17620573; 18055821; 17962469; 20079931; 21792230; 21987678; 22605927; 22665969
TUSC3	30242	7991	Mental retardation, autosomal recessive 7	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18452889; 18455129; 21739581
TWIST1	12428	7291	Saethre-Chotzen syndrome; Robinow-Sorauf syndrome; Craniosynostosis, isolated	AD	N/A	N/A	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal 	General	Syndromic forms can involve multiple congenital anomalies, as well as hearing impairment in some individuals	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1240778; 7120316; 7120317; 8968762; 8988167; 8988166; 9585583; 10465122; 11977182; 12116251; 11772178; 12791045; 16251895; 17437280; 17343269; 19373776; 20301368 
TWIST2	20670	117581	Setleis syndrome	AR	N/A	N/A	Craniofacial; Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14069095; 4412216; 3631024; 8818454; 12210295; 20691403; 21801849; 21931173 
TYK2	12440	7297	Immunodeficiency 35	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	17088085; 17521577; 18270328 
TYMP	3148	1890	Mitochondrial DNA depletion syndrome 1 (MNGIE type)	AR	N/A	N/A	Biochemical; Gastrointestinal; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9924029; 10852545; 12177387; 14757860; 16178026; 18787099; 19056268; 19853446; 21412940; 21794876 
TYR	12442	7299	Albinism, oculocutaneous, type IA; Albinism, oculocutaneous, type IB	AR	N/A	N/A	Dermatologic; Ophthalmologic	General	Variants may also be related to pigmentary manifestations such as skin, eye, and hair color, and related risk of skin cancer	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	666627; 1970634; 8477259; 8190479; 9158138; 17999355; 17952075;  18488028; 19533789; 18488027; 19578364; 20806075; 20861488; 21458243; 21541274; 22294196 
TYROBP	12449	7305	Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy; Nasu-Hakola disease 	AR	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10888890; 12370476; 15049507; 15883308; 17125796; 22082900 
TYRP1	12450	7306	Albinism, oculocutaneous, type III	AR	N/A	N/A	Dermatologic; Ophthalmologic	General	Variants may also be related to pigmentary manifestations such as skin, eye, and hair color, and related risk of skin cancer	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3935994; 8651291; 9345097; 16704458; 18680187; 19533799; 20861488; 21471978; 21996312; 22556244 
UBA1	12469	7317	Spinal muscular atrophy, X-linked 2, infantile	XL	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18179898
UBE2A	12472	7319	Mental retardation, X-linked, syndromic, Nascimento-type	XL	N/A	N/A	Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16909393; 20339384; 20412111; 21108393
UBE3A	12496	7337	Angelman syndrome	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8988171; 8988172; 9546330; 10196695; 11748306; 12210318; 15150776; 20034088; 20933619; 21072004; 21204213; 21362313; 21397058; 22065487 
UBE3B	13478	89910	Blepharophimosis-Ptosis-Intellectual-Disability Syndrome	AR	N/A	N/A	Craniofacial; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23200864
UBIAD1	30791	29914	Corneal dystrophy, crystalline, of Schnyder	AD	N/A	N/A	Ophthalmologic	General	Phototherapeutic keratectomy has been described as beneficial in this type of corneal dystrophy, though the advantage of early (genetic) diagnosis is unclear	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3486394; 8190477; 9450854; 10442892; 15034782; 17668063; 17962451; 18176953; 19429578; 19649163; 20489584; 20505825; 22065921 
UBQLN2	12509	29978	Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21857683; 24771548
UBR1	16808	197131	Johanson-Blizzard syndrome	AR	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Cardiovascular; Endocrine; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic	Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Gastrointestinal; Hematologic		Medical treatment of exocrine pancreatic insufficiency can be beneficial; Awareness of cardiovascular manifestastions (which can include structural malformations as well as cardiomyopathy) can allow early diagnosis and treatment; As the condition can include congenital deafness, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Treatment of endocrine manifestations, such as hypothyroidism, growth hormone deficiency, and diabetes mellitus, can be beneficial; Severe anemia requiring transfusions has been described, and awareness may allow prompt diagnosis and treatment	5171616; 728568; 474625; 4050852; 2645405; 12535044; 12725595; 14647752; 15379429; 16311597; 16632090; 17378628; 18553553; 19058315; 19006206; 19717322; 20556423; 21931868; 20556422; 21429315; 21711208; 22072859; 23463671; 23778732; 24052374
UCHL1	12513	7345	Parkinson disease 5, autosomal dominant; Neurodegeneration with optic atropy, childhood-onset	AD/AR	N/A	N/A	Neurologic; Ophthalmologic	General	For Parkinson disease 5, autosomal dominant, findings have not been replicated, and gene association has been described as uncertain, though levodopa-response has been reported	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9774100; 16450370; 23359680 
UGT1A1	12530	54658	Crigler-Najjar syndrome, type I; Crigler-Najjar syndrome, type II; Gilbert syndrome	AD/AR	Pediatric	Allelic with Breast milk jaundice (AD/AR)	Gastrointestinal	Gastrointestinal; Pharmacogenomic		In CNI, phototherapy (or other interventions, such as plasmapharesis), followed by liver transplantation may be beneficial; In CNII, not all individuals have severe forms of disease necessitating treatment, but patients with severe forms typically respond to phenobarbital treatment; Knowledge of the cause of jaundice even in less severe cases can help avoid prolonged etiologic work-ups; While Gilbert syndrome is not as severe as other disorders of hyperbilirubinemia, drug metabolism related to certain medications (eg, acetaminophen, atazanavir, irinotecan) imay be affected, and medication and dosing choice may be beneficial	12983120; 5685361; 805737; 3546653; 1734381; 1531971; 8276413; 7989595; 7565971; 8528206; 8690398; 9413009; 9580649; 9621515; 10412811; 11003624; 11061796; 11316168; 11370628; 11906189; 16712705; 18518849; 22676194; 22710376; 23099197; 23162302; 23241680; 23279026; 23403257; 23430851; 23926009; 23992562; 24065680
UMOD	12559	7369	Familial juvenile hyperuricemic nephropathy; Glomerulocystic kidney disease with hyperuricemia and isosthenuria	AD	Pediatric	Allelic with Medullary cystic kidney disease 2 (AD)	Renal	Renal	In some forms of MCKD2, it appears that isolated cysts can occur without hyperuricemia	In Glomerulocystic kidney disease with hyperuricemia and isosthenuria and Familial juvenile hyperuricemic nephropathy, medical treatment may be beneficial (eg, allopurinol related to gout and preservation of renal function)	7396593; 1975911; 1873940; 9266353; 9686952; 10780922; 12205338; 12471200; 14570709; 12634862; 12629136; 16883323
UMPS	12563	7372	Orotic aciduria	AR	Pediatric		Allergy/Immunology/Infectious; Biochemical; Hematologic; Neurologic	Biochemical		Pyrimidine replacement therapy, along with urinary orotic acid monitoring, can be beneficial	13651334; 14110033; 5347440; 6828110; 6717503; 9042911; 19562503 
UNC119	12565	9094	Immunodeficiency 13	AR	Pediatric	Allelic with Cone-rod dystrophy 2 (AD)	Ophthalmologic	General		In Immunodeficiency 13, the described invidiual suffered from frequent and severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	11006213; 22184408
UNC13D	23147	201294	Hemophagocytic lymphohistiocytosis, familial 3	AR	Pediatric		Allergy/Immunology/Infectious; Hematologic; Oncologic	Allergy/Immunology/Infectious; Hematologic; Oncologic		Early recognition may allow prompt treatment, as individuals frequently have fatal outcomes unless treated by control of infectious triggers and chemoimmunotherapy, followed by HSCT	14622600; 16825436; 16278825; 17993578; 20301617; 21881043; 21303357; 21755595; 21931115; 22146525; 21674762 
UNC93B1	13481	81622	Herpes simplex encephalitis, susceptibility to, 1	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals may be susceptible to severe HSV infections, which can result in lethal sequlae or severe chronic impairment, and recognition may allow preventive measures as well as prompt treatment with anti-HSV medications (eg, acyclovir), which may improve outcome	16973841
UNG	12572	7374	Immunodeficiency with hyper-IgM, type 5	AD	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Due to low/absent serum IgG, IgA, and IgE, Individuals are susceptible to recurrent/severe bacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	12958596; 15358621 
UPB1	16297	51733	Beta-ureidopropionase deficiency	AR	N/A	N/A	Biochemical; Neurologic	General	As with many disorders involving seizure risk, optimal control is beneficial; Normal neurologic development has been described (in addition to severe neurologic manifestations)	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15385443; 17964839; 22525402 
UPF3B	20439	65109	Mental retardation, X-linked, syndromic 14	XL	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General	Nonsyndromic forms have been described in addition to the initial reports of individuals with syndromic mental retardation	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9805132; 17704778; 19377476; 22957832
UPK3A	12580	7380	Renal/urogenital adysplasia	AD	N/A	N/A	Genitourinary; Renal	General	The condition has been described as involving progressive, inexorable renal failure, and renal transplant has been described	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15888565
UQCC2	21237	84300	Mitochondrial complex III deficiency, nuclear type 7	AR	N/A	N/A	Biochemical; Neurologic; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24385928
UQCC3	34399	790955	Mitochondrial complex III deficiency, nuclear type 9	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	25008109
UQCRB	12582	7381	Mitochondrial complex III deficiency	AR	N/A	N/A	Biochemical; Gastrointestinal	General	Individuals may suffer acute episodes of metabolic crisis; Treatment with "Mitochondrial cocktail" type therapy may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12709789
UQCRC2	12586	7385	Mitochondrial Complex III Deficiency, nuclear type 5	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23281071
UQCRQ	29594	27089	Mitochondrial complex III deficiency	AR	N/A	N/A	Biochemical; Neurologic	General	Individuals may suffer acute episodes of metabolic crisis; Treatment with "Mitochondrial cocktail" type therapy may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18439546
UROC1	26444	131669	Urocanase deficiency	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	5124677; 6107814; 19304569
UROD	12591	7389	Porphyria, hepatoerythropoietic; Porphyria cutanea tarda 	AD/AR	Pediatric		Biochemical; Dermatologic; Gastrointestinal; Hematologic	Dermatologic; Hematologic; Pharmacogenomic		Treatment involves management of iron overload (eg, by phlebotomy); Exacerbating factors (eg, iron overload, excessive alcohol use, polyhalogenated aromatic chemicals, estrogens, etc.) should be avoided; Skin protection is warranted	5697519; 5455563; 4640947; 5080345; 4729688; 4739135; 993332; 871403; 730158; 661929; 758588; 463934; 253381; 7369748; 7428280; 6112327; 7062951; 7059676; 6375356; 3775362; 3808000; 3821794; 3348969; 2920211; 1442894; 8644733; 9792863; 12030801; 17295179; 20955974; 21668429; 22382040; 23545314
UROS	12592	7390	Porphyria, congenital erythropoietic	AR	Pediatric		Dermatologic; Hematologic	Dermatologic; Hematologic		Transfusions can be beneficial; Individuals can prevent with bleeding diatheses, and prompt treatment may be beneficial; Limitation to sun exposure may be beneficial due ot photosensitivity; Manifestations such as thrombocytopenia and hemolytic anemia, may be effectively treated by splenectomy; Use of oral sorbents have been described; BMT has been described in severe cases	7205063; 3960070; 3100953; 2331520; 2207013; 8829650; 9834209; 12060112; 15703981; 22090724; 22350154; 22816431; 23557135; 23626549
USB1	25792	79650	Poikiloderma with neutropenia	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic	Allergy/Immunology/Infectious	Individuals may also be at risk for leukemia and related processes	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	18925663; 20004881; 20503306
USH1C	12597	10083	Usher syndrome, type IC; Deafness, autosomal recessive 18	AR	Pediatric		Audiologic/Otolaryngologic; Ophthalmologic	Audiologic/Otolaryngologic	Hearing loss has been described as late-onset in some individuals	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	5937908; 9653658; 10973248; 10973247; 12107438; 2136232; 23251578 
USH1G	16356	124590	Usher syndrome, type 1G	AR	Pediatric		Audiologic/Otolaryngologic; Ophthalmologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	12588794
USH2A	12601	7399	Usher syndrome, type 2A	AR	Pediatric	Allelic with Retinitis pigmentosa 39 (AR)	Audiologic/Otolaryngologic; Ophthalmologic	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; It has been suggested that  that stapes surgery should not be performed due to a high likelihood of complications (the use of cochlear implants has been reported as beneficial)	1580321; 9624053; 10775529; 10729113; 12427073; 15015129; 16301217; 16098008; 15671307; 17085681; 17296898; 18273898; 19881469; 20440071; 20301515 
USP9X	12632	8239	Mental retardation, X-linked 99	XL	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19377476; 24607389
USP9Y	12633	8287	Spermatogenic failure, Y-linked, 2	YL	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9384609; 10402373; 10507722; 10581029; 10767340; 16893908; 18205040; 19246359
UVSSA	29304	57654	UV-sensitive syndrome 3	AR	N/A	N/A	Dermatologic	General	Increased risk of skin tumors has not been reported	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7513056; 3974603; 3774595; 22466610; 22466612 
VAMP1	12642	6843	Spastic ataxia 1, autosomal dominant	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11774073; 22958904
VANGL1	15512	81839	Caudal regression syndrome; Neural tube defects	AD	N/A	N/A	Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17409324
VANGL2	15511	57216	Neural tube defects 	AD	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20558380; 20738329
VAPB	12649	9217	Amyotrophic lateral sclerosis 8; Spinal muscular atrophy, late-onset, Finkel type	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15372378; 18322265; 20940299; 20577002
VARS2	21642	57176	Combined oxidative phosphorylation deficiency 20	AR	N/A	N/A	Biochemical; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24827421; 25058219
VAX1	12660	11023	Microphthalmia, syndromic 11	AR	N/A	N/A	Craniofacial; Neurologic; Ophthalmologic	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22095910
VCAN	2464	1462	Wagner syndrome 1	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9098284; 16043844; 16636652; 19901218; 20301747; 21738396; 22739342
VCL	12665	7414	Cardiomyopathy, familial hypertrophic 15; Cardiomyopathy, dilated, 1W	AD	Adult		Cardiovascular	Cardiovascular		Surveillance (including with echocardiography, as asymptomatic individuals with mutations have been found to have detectable disease prior to clinical presentation), preventive measures, and early medical management may be helpful to help decrease morbidity and mortality related to cardiomyopathy	11815424; 16712796; 16236538
VCP	12666	7415	Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7182974; 15034582; 16247064; 18260132; 18341608; 19704082; 19380227; 21145000; 21320982; 21984748; 23152587 
VDR	12679	7421	Vitamin D-dependent rickets, type 2A	AD/AR	Pediatric		Dermatologic; Endocrine; Musculoskeletal	Endocrine		Treatment of manifestations such as rickets (eg, with vitamin D3, calcium, phosphate) can be beneficial in some individuals, though not all individuals have been reported as demonstrating clinical or laboratory-based response to treatments	205789; 233695; 221630; 6102232; 7318845; 3009551; 3024987; 3040300; 2849209; 2551693; 9005998; 17970811; 19815438; 19921089; 21073129; 21424181; 21590741; 21812032; 21860566; 22145479; 22145480; 23026218
VEGFC	12682	7424	Lymphedema, hereditary, ID	AD	N/A	N/A	Dermatologic	General	Individuals may be susceptible to recurrent skin infections	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23410910; 24744435
VHL	12687	7428	Von Hippel Lindau; Erythrocytosis, familial, 2 (Chuvash polycythemia); Pheochromocytoma	AD/AR	Pediatric		Cardiovascular; Hematologic; Oncologic	Cardiovascular; Hematologic; Oncologic	Depending on the condition, individuals can have primarily oncologic (Von Hippel Lindau) or hematologic (Chuvash polycythemia) manifestations	In VHL, surveillance for and early treatment of malignant complications (eg, hypertension and hypokalemia resulting from pheochromocytoma, as in isolated Pheochromocytoma) may be beneficial; Individuals with Erythrocytosis, familial, 2 have a high risk for peripheral thrombosis and cerebrovascular events, and preventive measures and early treatment may be beneficial, though the efficacy of interventions such as phlebotomy is questionable	13494077; 14142412; 4453572; 449657; 573913; 431135; 3790978; 2897130; 3200963; 2642584; 2066108; 1673491; 1347089; 1593692; 1436350; 8493574; 7987306; 7977949; 8059782; 8069305; 8592333; 8825918; 8929948; 9329368; 9398721; 9145719; 9058738; 9215674; 9663592; 10408776; 10554035; 10697963; 10830910; 11106358; 11097604; 10631138; 11688380; 11987242; 12415268; 12629069; 12844285; 14500227; 14726398; 15190140; 14695531; 14711727; 15599750; 15642664; 16210343; 17057815; 16518846; 17609489; 17311301; 19464396; 20151405; 20301636; 21606165; 21713522; 21972040; 21993671; 22265326; 22393103; 23781388; 23827964; 23897319; 23968328
VIM	12692	7431	Cataract, pulverulent, autosomal dominant	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19126778
VIPAS39	20347	63894	Arthrogryposis, renal dysfunction, and cholestasis 2	AR	N/A	N/A	Gastrointestinal; Musculoskeletal; Renal	General	The condition can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20190753; 23636179
VKORC1	23663	79001	Vitamin K-dependent clotting factors, combined deficiency of, 2; Drug metabolism, VKORC1-related	AD/AR	Pediatric		Hematologic	Hematologic; Pharmacogenomic		Individuals may present with severe bleeding episodes (including, for example, fatal neonatal intracranial hemorrhage), and oral administration of vitamin K typically reverses bleeding tendency; Variants may have pharmacogenomic relevance (related to Drug metabolism, VKORC1-related) in regards to selection and dosing of medications (including warfarin) 	11154138; 12384421; 14765194; 15930419; 15947090; 15888487; 16611310; 17653141; 18466099; 18535201; 18855533; 19207028; 19228618; 19300499; 20203262; 20833980; 19794411; 21148049; 22431865; 22528326; 23215886; 23276529; 23277416; 23279643; 23677510
VLDLR	12698	7436	Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 1	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16080122; 18043714; 18326629; 18364738; 20082205
VPS13A	1908	23230	Choreoacanthocytosis	AR	N/A	N/A	Hematologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4255726; 5677189; 4647152; 666266; 7081216; 7073550; 4026606; 1998879; 7936287; 8599563; 9382101; 10371080; 11381253; 11381254; 12404112; 15918062; 15824261; 17998451; 18584183; 18661137; 20301561; 21598378; 22038564; 23199253
VPS13B	2183	157680	Cohen syndrome	AR	Pediatric		Allergy/Immunology/Infectious; Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic	Allergy/Immunology/Infectious	The condition may be frequently recognizable due to characteristic features, including dysmorphisms	Though the condition may be frequently recognizable, individuals can have recurrent infections, and antiinfectious prophlyaxis and treatment (including G-CSF for neutropenia), as well as early and aggressive treatment of infections may be beneficial	4717588; 671157; 7438489; 7246618; 7166592; 6705238; 3989828; 3656371; 3223494; 9266925; 10466416; 10964838; 12676892; 12730828; 15211651; 15025727; 15141358; 20683995; 20301655; 20921020; 24311531
VPS35	13487	55737	Parkinson disease 17	AD	N/A	N/A	Neurologic	General	Individuals have been described with levodopa response 	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	18342564; 21763482; 21763483; 22517097; 23408866; 23623008
VPS37A	24928	137492	Spastic paraplegia 53, autosomal recessive	AR	N/A	N/A	Neurologic	General		The use of botulinum has been described as beneficial for treating spasticity in some individuals, though the advantage of genetic diagnosis is unclear; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22717650
VPS39	20593	23339	Schizophrenia	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23042115
VPS45	14579	11311	Neutropenia, neutrophil dysfunction, bone marrow fibrosis, and nephromegaly	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Individuals have been described with frequent and severe infections, and awareness may allow prophylactic measures (including treatment with G-CSF), as well as early and aggressive treatment of infections; HSCT has been described	23738510
VPS53	25608	55275	Pontocerebellar hypoplasia, type 2E	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24577744
VRK1	12718	7443	Pontocerebellar hypoplasia type 1A	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19646678; 21937992
VSX1	12723	30813	Craniofacial anomalies and anterior segment dysgenesis syndrome; Keratoconus 1; Corneal dystrophy, posterior polymorphous	AD	N/A	N/A	Craniofacial; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11978762; 15051220; 15623752; 16735990; 18216574; 18626569; 19763142; 19956409; 20664914; 21365019; 21976959
VSX2	1975	338917	Microphthalmia, isolated 2; Microphthalmia, isolated, with coloboma 3 	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3378363; 10932181; 15257456; 17661825; 18648522 
VWF	12726	7450	von Willebrand disease, type 1; von Willebrand disease, type 2A; von Willebrand disease, type 3	AD	Pediatric		Hematologic	Hematologic; Pharmacogenomic		There are a number of treatments depending on the subtype of disease; Treatments include control of severe bleeding episodes (eg, with IV infusion of plasma-derived clotting factor, or IV/SQ desmopressin), as well as fibrinolytic inhibitors and hormones for menorrhagia; Primary prevention can be instituted via prophylactic VWF/FVIII infusions; Among a number of important preventive measures, specific medications should be avoided, including ASA, clopidogrel, NSAIDS	315519; 6972630; 6412139; 3116703; 3033024; 3257148; 3258663; 2895123; 2297569; 8456431; 8456432; 8367445; 8052974; 8839833; 9253800; 10444292; 10669167; 11756169; 12649144; 15306670; 17080221; 16889557; 16985174; 17190853; 19085649; 20409624; 22428722; 22458923; 22482515; 22531022; 22530576; 22722677; 22726101; 22823000; 22906074; 22957493; 23034827; 23109357; 23109385 
WAS	12731	7454	Wiskott-Aldrich syndrome; Thrombocytopenia 1; Neutropenia, severe congenital, X-linked	XL	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Hematologic	Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic	Individuals can have immune dysfunction, such as in SCNX, which is due to constitutively activating mutations	Prophylaxis and early and aggressive treatments for infections, and avoidance of circumstances that would result in severe bleeding, including certain medications, may be beneficial; HSCT, and genetically modified HSCT (gene therapy) have been described	13133561; 4177931; 4177932; 3995178; 3284030; 1960605; 8279047; 8069912; 7795648; 7537115; 1611094; 7579347; 8682510; 10575547; 8931701; 10447259; 11242115; 11447283; 15142877; 11238097; 11242115; 16804117; 17065640; 17065636; 17250667; 19006568; 18724301; 18479478; 20301357; 21067383; 22052860; 22338148; 22426750; 22456069; 22523910; 23023736; 23237501; 23264593; 23343520; 23498591; 23527602; 23845947; 23943155
WDPCP	28027	51057	Bardet-Biedl syndrome 15; Meckel-Gruber syndrome type 6, modifier of	AR	N/A	N/A	Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	General	Variants may modify severity of BBS and related disorders due to mutations in other BBS-associated genes	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20671153
WDR11	13831	55717	Hypogonadotropic hypogonadism; Kallmann syndrome	AD	Pediatric		Endocrine; Neurologic	General	Surveillance in adolescence related to sexual maturation is indicated, and in order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to  fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	Monitoring of bone mineral density is indicated in order to allow early detection and treatment of disease	20887964
WDR19	18340	57728	Short-rib thoracic dysplasia 5 with or without polydactyly; Cranioectodermal dysplasia 4; Nephronophthisis 13; Retinitis pigmentosa; Senior-Loken syndrome	AD/AR	N/A	N/A	Cardiovascular; Craniofacial; Dental; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary; Renal	General	The conditions can involve multiple congenital anomalies; Renal transplantation has been described	Genetic knowledge may potentially be beneficial related to manifestations such as renal issues; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19430947; 21378380; 22019273; 23559409; 23683095
WDR34	28296	89891	Short -rib thoracic dysplasia 11 with or without polydactyly	AR	N/A	N/A	Musculoskeletal; Ophthalmologic; Renal	General		Genetic knowledge may potentially be beneficial related to manifestations such as renal issues; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24183449; 24183451
WDR35	29250	57539	Cranioectodermal dysplasia 2; Short -rib thoracic dysplasia 7 with or without polydactyly	AR	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Renal	General		The condition can include cardac defects and renal and hepatic disease, among other findings; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20817137; 21378380; 21473986 
WDR45	28912	11152	Neurodegeneration with brain iron accumulation 5	XL	N/A	N/A	Neurologic	General		Genetic knowledge may potentially be beneficial related to manifestations such as renal issues; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21920862; 22892189; 23176820; 23435086; 23447832; 23687123
WDR60	21862	55112	Short -rib thoracic dysplasia 8 with or without polydactyly	AR	N/A	N/A	Cardiovascular; Gastrointestinal; Genitourinary; Musculoskeletal; Pulmonary; Renal	General	The condition may involve multiple malformations	Genetic knowledge may potentially be beneficial related to manifestations such as renal issues; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23910462
WDR62	24502	284403	Microcephaly 2, primary, autosomal recessive, with or without cortical malformations	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10573015; 20729831; 20890279; 20890278; 21496009; 21834044; 21961505; 22308068; 23065275
WDR72	26790	256764	Amelogenesis imperfecta, hypomaturation type, IIA3	AR	N/A	N/A	Dental	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19853237; 22243262; 23293580
WFS1	12762	7466	Wolfram syndrome 	AR	Pediatric	Allelic with Wolfram-like syndrome, autosomal dominant (AD); Deafness, autosomal dominant 6/14/38 (AD); Cataract 41 (AD)	Audiologic/Otolaryngologic; Endocrine; Neurologic; Ophthalmologic; Renal	Audiologic/Otolaryngologic; Endocrine; Renal	A small proportion of individuals may have congenital deafness	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Recognition and interventions related to endocrine anomalies (eg, diabetes insipidus, diabetes mellitus) may be beneficial; Awareness of the possibility of renal anomalies (eg, hydronephrosis) may allow surveillance and management to potentially benefit renal/urologic function	5956444; 8595423; 9817917; 10521293; 11709537; 11317350; 11709538; 12107816; 12181639; 15070927; 16151413; 17568405; 17492394; 18806274; 21823543; 21917145; 21446023; 22238590; 21968327; 22498363; 22226368; 23531866
WIPF1	12736	7456	Wiskott-Aldrich syndrome 2	AR	Pediatric		Allergy/Immunology/Infectious; Dermatologic; Hematologic 	Allergy/Immunology/Infectious; Hematologic		Individuals have been described with frequent and severe infections (including a lethal infectious course in one individual), and thus, antiinfectious prophylaxis and early and aggressive treatment of infections and bleeding issues may be beneficial; Unrelated CBT has been reported as effective	22231303
WISP3	12771	8838	Spondyloepiphyseal dysplasia tarda with progressive arthropathy; Arthropathy, progressive pseudorheumatoid, of childhood	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	6807993; 6410512; 6873109; 6431106; 8275575; 9222963; 10471507; 16152649; 19064006; 21528827 
WNK1	14540	65125	Pseudohypoaldosteronism, type IIC; Neuropathy, hereditary sensory and autonomic, type II	AD/AR	Pediatric		Neurologic; Renal	Neurologic; Renal		Treatment (eg, correction of physiologic abnormalities by thiazide diuretics) can be effective, and measures towards optimizing blood pressure can decrease morbidity and mortality related to potential sequale of hypertension; In  Neuropathy, hereditary sensory and autonomic, type IIl, reduced pain sensation may result in injury, as well as result in ulceration/infection, and precautions may be beneficial	20323803; 10869238; 11498583; 15060842; 5455397; 15911806; 16946995; 16636245; 16534117; 18521183; 22080857; 22266938; 21768522; 22073419; 22910560; 22934535 
WNK4	14544	65266	Pseudohypoaldosteronism, type IIB	AD	Pediatric		Renal	Renal		Treatment (eg, correction of physiologic abnormalities by thiazide diuretics) can be effective, and measures towards optimizing blood pressure can decrease morbidity and mortality related to potential sequale of hypertension	718349; 718348; 504550; 6103235; 9171836; 11498583; 19016006; 22266938; 22073419
WNT1	12774	7471	Osteoprosis, autosomal dominant; Osteogenesis imperfecta, type XV	AD/AR	N/A	N/A	Musculoskeletal	General	The use of bisphosphonates has been described to treat osteogenesis imperfecta, but it is unclear if an early (genetic) diagnosis would be advantageous	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23434763; 23499309; 23499310; 23656646
WNT10A	13829	80326	Odontoonychodermal dysplasia; Schopf-Schulz-Passarge syndrome; Tooth agenesis, selective, 4 	AD/AR	N/A	N/A	Dental; Dermatologic 	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	4281327; 6837628; 15316967; 17847007; 19471313; 19559398; 20163410; 20418069; 21143469; 21484994; 21834823; 24449199
WNT10B	12775	7480	Split-hand/foot malformation 6	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12072797; 18515319; 20635353; 21554266
WNT3	12782	7473	Tetraamelia, autosomal recessive	AR	N/A	N/A	Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Renal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14872406
WNT4	12783	54361	Mullerian aplasia and hyperandrogenism; 46,XX sex reversal with dysgenesis of kidneys, adrenals, and lungs (SERKAL syndrome)	AD/AR	N/A	N/A	Cardiovascular; Endocrine; Genitourinary; Musculoskeletal; Pulmonary; Renal	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15317892; 16959810; 18179883; 18182450
WNT5A	12784	7474	Robinow syndrome, autosomal dominant 	AD	N/A	N/A	Cardiovascular; Craniofacial; Dental; Genitourinary; Musculoskeletal; Renal	Renal		Individuals have been described with high-grade vesicoureteral reflux, and surveillance and management may be helpful to preserve renal function	5771504; 3746837; 17256787; 19918918
WNT7A	12786	7476	Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome; Fuhrmann syndrome	AR	N/A	N/A	Dermatologic; Genitourinary; Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	7363910; 3981578; 3400735; 3066902; 2338339; 1785629; 9128926; 11332978; 12868468; 16826533; 19309796; 20949531; 21271649; 21344627
WRAP53	25522	55135	Dyskeratosis congenita, autosomal recessive 3	AR	Pediatric		Dermatologic; Hematologic; Oncologic; Pulmonary	Hematologic; Oncologic; Pulmonary		Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; Lung transplant may be indicated in individuals with advanced lung diease; HSCT may be indicated due to manifestations including leukemia and bone marrow failure (which may also be treated with androgen therapy), but the long-term efficacy may not be optimal	21205863; 20301779 
WRN	12791	7486	Werner syndrome	AR	Pediatric		Cardiovascular; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Musculoskeletal; Obstetric; Oncologic; Ophthalmologic	Cardiovascular; Endocrine; Obstetric; Oncologic		Individuals typically have insulin resistance, as well as increased risk of atherosclerosis and malignancy (eg, melanomas, osteosarcomas, sarcomas, and thyroid carcinoma) and and awareness may allow preventive measures related to the risk of atherosclerosis, as well as early diagnosis and treatment of atherosclerosis,  diabetes mellitus, and malignancy, which may reduce morbidity and mortality; Awareness and interventions related to endocrine complications (eg, metformin treatment for insulin resistance) as well as the potential for obstetric sequelae (eg, cervical incompetence) may be beneficial in the management of reproductive health	14042963; 7460386; 8722214; 8968742; 8602509; 9048918; 9253306; 9012406; 10220139; 16786514; 17476199; 18205852; 20301687; 20443122; 22654791; 23524889; 23552003; 23849162; 23936869
WT1	12796	7490	Denys-Drash syndrome; Wilms tumor, type 1; Frasier syndrome	AD	Pediatric	Allelic with Meacham syndrome, which involves multiple malformations, but typically does not involve findins such as Wilms tumor (AD); Allelic with Nephrotic syndrome, type 4 (AD), though it is unclear if this disorder typically occurs without oncologic manifestations	Cardiovascular; Endocrine; Genitourinary; Oncologic; Renal; Pulmonary	Oncologic; Renal		Individuals are at risk for several types of neoplasm, and surveillance may allow early detection and treatment for common oncologic features (eg, Wilms tumor, gonadoblastoma); Renal transplant may be indicated (and beneficial) in individuals with end-stage renal faiure	14149008; 4292870; 4316066; 4153449; 331956; 3000666; 3130865; 3026952; 2172500; 1655284; 1338906; 1338905; 8386697; 8071974; 7645607; 7607640; 9398852; 9108089; 9529364; 9607189; 11241056; 12050205; 17853480; 18203154; 18688870; 20150449; 20301471; 21434831; 21559934; 21614510; 22585769; 22876585; 24161391
WWOX	12799	51741	Spinocerebellar ataxia, autosomal recessive 12	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17470496; 24369382
XDH	12805	7498	Xanthinuria, type I	AR	Pediatric		Biochemical; Musculoskeletal; Renal	Biochemical; Renal		Dietary measures (eg, purine restricted, increased fluid intake) and medical measures (eg, allopurinol) can be effective	13118765; 861350; 3818951; 3339736; 754557; 9767921; 9153281
XG	12806	7499	XG blood group	BG	Pediatric		Hematologic	General		Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	7533029
XIAP	592	331	Lymphoproliferative syndrome, X-linked, 2	XL	Pediatric		Allergy/Immunology/Infectious; Hematologic; Oncologic	Allergy/Immunology/Infectious; Hematologic; Oncologic	Digenic disease (with CD40LG) have been reported	Surveillance for EBV infections is indicated; Prompt recognition and treatment of hemophagocytic lymphohistiocytosis (with immunosuppressive agents or rituximab in the case of EBV infection); Treatment for individuals with hypogammaglobulinemia (with IVIG) may be beneficial; Awareness of the increased risk of lymphoma may allow prompt recognition and treatment; HSCT has been described, and is indicated in many individuals 	17080092; 20301580; 21119115; 21543760; 21971331 
XIST	12810	7503	X-inactivation, familial skewed, 1	XL	N/A	N/A	General	General	It has been suggested that the condition may be related to reproductive outcomes, but the evidence is mixed	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	8825575; 9354806; 10090877; 10441596; 15731119; 19646676
XK	12811	7504	McLeod syndrome	XL	Pediatric		Cardiovascular; Hematologic; Musculoskeletal; Neurologic	Cardiovascular		Surveillance for cardiovascular disease (eg, dilated cardiomyopathy and arrhythmias)  and early medical treatment may reduce morbidity	13860532; 8004674; 11261514; 11761473; 17683354; 21463873 
XPA	12814	7507	Xeroderma pigmentosum, group A	AR	Pediatric		Dermatologic; Neurologic; Oncologic	Dermatologic; Neurologic; Oncologic; Ophthalmologic		Skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance (primarily related to skin manifestations, as well as other sequelae) can be beneficial	286113; 2168777; 2234061; 1571258; 1372102; 8053698; 9671271; 10447254; 20301571; 20534089; 20574439; 22044607; 22081045 
XPC	12816	7508	Xeroderma pigmentosum, group C	AR	Pediatric		Dermatologic; Oncologic	Dermatologic; Neurologic; Oncologic; Ophthalmologic		Skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance (primarily related to skin manifestations, as well as other sequelae) can be beneficial	7389185; 6696469; 8298653; 9804340; 10766188; 11511294; 14662655; 20301571; 21482201; 22211393; 23143338; 23173980; 23436679
XPNPEP2	12823	7512	Angioedema induced by ACE inhibitors, susceptibility to	XL	Pediatric		General	Pharmacogenomic		Medication selection would be impacted in mutation-positive individuals	16175507
XPNPEP3	28052	63929	Nephronophthisis-like nephropathy 1	AR	N/A	N/A	Audiologic/Otolaryngologic; Neurologic; Renal	General	Avoidance of nephrotoxic medications may be beneficial	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20179356
XYLT1	15516	64131	Desbuquois dysplasia 2	AR	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23982343; 24581741
YAP1	16262	10413	Ocular coloboma with or without hearing impairment, cleft lip/palate, and/or mental retardation	AD	Pediatric		Audiologic/Otolaryngologic; Craniofacial; Neurologic; Ophthalmologic; Renal	Audiologic/Otolaryngologic		Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	24462371
YARS	12840	8565	Charcot-Marie-Tooth disease, dominant intermediate C	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14606043; 16429158
YARS2	24249	51067	Myopathy, lactic acidosis, and sideroblastic anemia 2	AR	Pediatric		Cardiovascular; Hematologic; Musculoskeletal	Cardiovascular; Hematologic		Individuals may develop transfusion-dependent sideroblastic anemia in infancy; Surveillance for cardiovascular manifestations may allow early medical interventions	20598274; 22504945; 24344687; 24430573
ZAP70	12858	7535	Selective T-cell defect	AR	Pediatric		Allergy/Immunology/Infectious	Allergy/Immunology/Infectious		Prophylactic measures, in the short term, include IVIG administration as well as antiinfectious prophylaxis; If blood products are necessary, they should be irradiated and CMV and EBV-negative; Live vaccines should be avoided, and immunizations should be deferred until reconstitution of the immune system; HSCT has been described as effective in some individuals	2511270; 8124727; 8202713; 8202712; 10574909; 10748099; 11123350; 11412303; 11463783; 18509675; 19548248; 20301777; 23124046
ZBTB16	12930	7704	Skeletal defects, genital hypoplasia, and mental retardation	AR	N/A	N/A	Genitourinary; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11891687; 18611983
ZBTB18	13030	10472	Mental retardation, autosomal dominant 22	AD	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24193349
ZBTB20	13503	26137	Primrose syndrome	AD	N/A	N/A	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	25062845; 25017102
ZBTB24	21143	9841	Immunodeficiency-Centromeric Instability-Facial Anomalies	AR	Pediatric		Allergy/Immunology/Infectious; Craniofacial; Neurologic	Allergy/Immunology/Infectious	The condition may be recognizable due to features including dysmorphic facial features and developmental delay 	Individuals may demonstrate agammaglobulinemia/hypogammaglobulinemia, resulting in recurrent/severe (including fatal) respiratory and GI infections , and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial in order to decrease morbidity and mortality	21596365
ZDHHC15	20342	158866	Mental retardation, X-linked 91	XL	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	15915161
ZDHHC9	18475	51114	Mental retardation, X-linked syndromic, Raymond type	XL	N/A	N/A	Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	17436253; 19377476
ZEB1	11642	6935	Corneal dystrophy, Fuchs endothelial 6; Corneal dystrophy, posterior polymorphous, 3	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12654361; 16252232; 20036349; 21067486; 22199242; 23599324; 23662738; 23807282
ZEB2	14881	9839	Mowat-Wilson syndrome	AD	N/A	N/A	Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	General	The conditions can involve multiple congenital anomalies	The condition can include Hirschsprung disease, among other multi-systemic manifestations; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9719364; 11448942; 11279515; 14679597; 15121779; 16088920; 16688751; 16532472; 17203459; 19215041;20301585; 21343952; 21497296; 22246645; 22486326; 23322667; 23427518; 23466526; 23523603; 24029077; 24715670
ZFP57	18791	346171	Diabetes mellitus, transient neonatal, 1	AD	Pediatric		Endocrine	Endocrine	The pathogenesis can involve imprinting defects (eg, paternal UPD, paternal duplication, methylation defects)	Individuals present early in life with failure to thrive, hyperglycemia, and dehydration, and prompt recognition and treatment can reduce morbidity	18622393
ZFPM2	16700	23414	46,XY sex reversal 9	AD	Pediatric	Allelic with Diaphragmatic hernia 3 (AD); Tetralogy of Fallot (AD)	Cardiovascular; Genitourinary; Musculoskeletal; Neurologic; Pulmonary	Oncologic	Mutations can result in multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14517948; 16103912; 17568391; 20807224; 24549039
ZFYVE26	20761	23503	Spastic paraplegia 15	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	11342696; 14745065; 17661097; 19438933; 18394578; 19805727
ZFYVE27	26559	118813	Spastic paraplegia 33, autosomal dominant	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16826525; 18606302
ZIC2	12873	7546	Holoprosencephaly 5	AD	N/A	N/A	Endocrine; Neurologic	General		Individuals with holoprosencephaly  may demonstrate endocrine anomalies, including diabetes insipidus; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	9771712; 11285244; 19955556; 20104608 
ZIC3	12874	7547	VACTERL association, X-linked, with or without hydrocephalus; Heterotaxy, visceral, 1, X-linked; Congenital heart defects, nonsyndromic, 1, X-linked 	XL	N/A	N/A	Cardiovascular; Genitourinary; Gastrointestinal; Musculoskeletal; Neurologic; Pulmonary; Renal	General	The conditions can involve multiple congenital anomalies	The condition can include structural heart anomalies as well as other manifestations; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	3674105; 9354794; 10980576; 14681828; 17295247; 20452998; 21465648; 21864452; 23427188; 24123890
ZIM2	12875	23619	Schizophrenia	AD	N/A	N/A	Neurologic	General		Evidence or clinical applicability unclear	21743468
ZMPSTE24	12877	10269	Mandibuloacral dysplasia with type B lipodystrophy; Restrictive dermopathy, lethal	AD/AR	N/A	N/A	Dental; Dermatologic; Musculoskeletal; Neurologic	General	The conditions can involve multiple congenital anomalies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	1642279; 12913070; 15317753; 16297189; 15843403; 18435794; 19504603; 20034068; 22495976
ZMYND10	19412	51364	Ciliary dyskinesia, primary, 22	AR	Pediatric		Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary		Pulmonary and audiologic surveillance may be beneficial to assess respiratory  and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of  respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations	20301301; 23891469; 23891471
ZMYND11	16966	10771	Mental retardation, autosomal domianant, 30	AD	N/A	N/A	Craniofacial; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	25217958
ZMYND15	20997	84225	Spermatogenic failure 14	AR	N/A	N/A	Genitourinary	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24431330
ZNF141	12926	7700	Postaxial polydactyly type A, autosomal recessive	AR	N/A	N/A	Musculoskeletal	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23160277
ZNF335	15807	63925	Microcephaly 10, primary, autosomal recessive	AR	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	23178126
ZNF41	13107	7592	Mental retardation, X-linked 89	XL	N/A	N/A	Neurologic	General	The evidence of mutations as being related to disease causation has been questioned due to subsequent population-based studies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	14628291; 23871722
ZNF423	16762	23090	Joubert syndrome 19; Nephronophthisis 14	AD/AR	N/A	N/A	Neurologic; Ophthalmologic; Pulmonary; Renal	General		The conditions can involve manifestations including renal disease and anomalous perinatal breathing; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	22863007
ZNF469	23216	84627	Brittle cornea syndrome 1	AR	Pediatric		Musculoskeletal; Ophthalmologic	Ophthalmologic		Individuals are prone to ophthalmologic injury (such as corneal rupture) with minimal trauma, and protective measures may be beneficial	13627089; 14218178; 5755738; 4872990; 5775573; 4691558; 962660; 7387950; 2112090; 2363420; 14679583; 18452888; 19661234; 20938016
ZNF480	23305	147657	Schizophrenia	AD	N/A	N/A	Neurologic	General		Evidence or clinical applicability unclear	21743468
ZNF513	26498	130557	Retinitis pigmentosa 58	AR	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	20797688; 20227676
ZNF565	26726	147929	Schizophrenia	AD	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21743468
ZNF592	28986	9640	Spinocerebellar ataxia, autosomal recessive 5	AR	N/A	N/A	Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	12030328; 20531441
ZNF644	29222	84146	Myopia 21, autosomal dominant	AD	N/A	N/A	Ophthalmologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	21695231
ZNF674	17625	641339	Mental retardation, X-linked 92	XL	N/A	N/A	Neurologic	General	The evidence of mutations as being related to disease causation has been questioned due to subsequent population-based studies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16385466; 23871722
ZNF711	13128	7552	Mental retardation, X-linked 97	XL	N/A	N/A	Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	19377476
ZNF750	25843	79755	Seborrhea-like dermatitis with psoriasiform elements	AD	N/A	N/A	Dermatologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	16751772
ZNF81	13156	347344	Mental retardation, X-linked 45	XL	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General	The evidence of mutations as being related to disease causation has been questioned due to subsequent population-based studies	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	10398246; 15121780; 23871722
ZP1	13187	22917	Oocyte maturation defect	AR	N/A	N/A	Obstetric	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	24670168
ZSWIM6	29316	57688	Acromelic frontonasal dysostosis	AD	N/A	N/A	Craniofacial; Musculoskeletal; Neurologic	General		Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	25105228
