HEART GENE PANEL DG 2.3.x

Transcription

1 HEART GENE PANEL DG 2.3.x Gene Median % covered > % covered > Associated Phenotype description and OMIM ID coverage 10x 20x AARS2 94,1 99% 98% Combined oxidative phosphorylation deficiency 8, ABCC6 52,8 71% 68% Arterial calcification generalized of infancy 2, Pseudoxanthoma elasticum, Pseudoxanthoma elasticum, forme fruste, ABCC % 97% Cardiomyopathy, dilated, 1O, Atrial fibrillation, familial, 12, Hypertrichotic osteochondrodysplasia, ACAN 128,5 95% 90% Spondyloepiphyseal dysplasia, Kimberley type, Spondyloepimetaphyseal dysplasia, aggrecan type, Osteochondritis dissecans, short stature, and early-onset osteoarthritis, ACE 90,8 93% 90% {Myocardial infarction, susceptibility to} {Alzheimer disease, susceptibility to}, {Microvascular complications of diabetes 3}, [Angiotensin I-converting enzyme, benign serum increase] {SARS, progression of} Renal tubular ACSF3 100,9 100% 99% Combined malonic and methylmalonic aciduria, ACTA2 85,2 100% 99% Aortic aneurysm familial thoracic 6, Moyamoya disease 5, Multisystemic smooth muscle dysfunction syndrome, ACTC1 91,4 100% 94% Cardiomyopathy, dilated, 1R, Cardiomyopathy, familial hypertrophic, 11, Atrial septal defect 5, Left ventricular noncompaction 4, ACTN1 100,9 100% 99% Bleeding disorder, platelet-type, 15, ACTN2 91,5 100% 96% Cardiomyopathy,dilated,1AA,with/without LVNC, Cardiomyopathy,hypertrophic,23,with/without LVNC, ACVR1 103,6 100% 100% Fibrodysplasia ossificans progressiva, ACVR2B 86,2 96% 96% Heterotaxy, visceral, 4, autosomal,

2 ADAMTS6 135,1 97% 96% No OMIM phenotype ADAMTS9 97,9 98% 93% No OMIM phenotype ADRB1 74,8 98% 92% [Resting heart rate], {Congestive heart failure and beta-blocker response,modifier of} ADRB2 154,1 100% 100% {Asthma, nocturnal, susceptibility to}, {Obesity, susceptibility to}, Beta-2-adrenoreceptor agonist, reduced response to AGL 145,5 100% 100% Sengers syndrome, Cataract, autosomal recessive congenital 5, AGT 139,6 100% 100% {Hypertension, essential, susceptibility to}, {Preeclampsia, susceptibility to} Renal tubular dysgenesis, AGTR1 151,3 100% 100% Hypertension, essential, AKAP9 136,9 100% 99% Long QT syndrome-11, ALDH1A2 96,8 100% 100% No OMIM phenotype ALMS1 206,5 98% 98% Alstrom syndrome, ANK2 135,8 100% 99% Long QT syndrome-4, Cardiac arrhythmia, ankyrin-b-related, ANKRD1 114,1 100% 100% No OMIM phenotype ANKS6 66,6 97% 85% Nephronophthisis 16, AP1B1 87,1 98% 88% No OMIM phenotype AP2B % 91% No OMIM phenotype APBB % 100% No OMIM phenotype ARMC4 100,3 89% 86% Ciliary dyskinesia, primary, 23, ATP1A4 108,4 99% 96% No OMIM phenotype BAG3 167,3 100% 100% Myopathy, myofibrillar, 6, Cardiomyopathy, dilated, 1HH, BICC % 99% {Renal dysplasia,cystic,susceptibility to},601331

3 BMPR2 162,2 100% 99% Pulmonary hypertension, familial primary, 1, with or without HHT, Pulmonary hypertension, primary, fenfluramine or dexfenfluramine-associated, Pulmonary venoocclusive disease, BRAF 84,6 98% 95% Melanoma, malignant, somatic Colorectal cancer, somatic Adenocarcinoma of lung, somatic, Nonsmall cell lung cancer, somatic Cardiofaciocutaneous syndrome, Noonan syndrome 7, LEOPARD syndrome 3, C1orf127 96,9 97% 92% No OMIM phenotype C5orf42 133,5 100% 100% Joubert syndrome 17, CACNA1B 99,2 96% 91%?Dystonia 23, CACNA1C 108,8 98% 96% Timothy syndrome, Brugada syndrome 3, CACNA1D % 97% Sinoatrial node dysfunction and deafness, CACNA2D1 97,2 100% 100% No OMIM phenotype CACNB2 127,4 100% 100% Brugada syndrome 4, CALM1 115,1 100% 100% Ventricular tachycardia, catecholaminergic polymorphic, 4, CALM2 68,7 67% 67% Long QT syndrome 15, CALM3 118,6 99% 99% No OMIM phenotype CALR3 100,4 100% 100% Cardiomyopathy, familial hypertrophic, 19, CAPN3 117,2 99% 97% Muscular dystrophy, limb-girdle, type 2A, CASQ2 98,7 100% 97% Ventricular tachycardia, catecholaminergic polymorphic, 2, CAV3 154,1 100% 100% Muscular dystrophy, limb-girdle, type IC, Rippling muscle disease, Creatine phosphokinase, elevated serum, Myopathy, distal, Tateyama type, Cardiomyopathy, familial hypertrophic, Long QT syndrome-9, CBL % 100% Noonan syndrome-like disorder with/without juvenile myelomonocytic leukemia,

4 CBS 85,2 100% 93% Homocystinuria, B6-responsive and nonresponsive types, Thrombosis, hyperhomocysteinemic, CC2D2A 101,8 98% 97% COACH syndrome, Joubert syndrome 9, Meckel syndrome 6, CCDC ,9 95% 95% Ciliary dyskinesia,primary,30, CCDC39 111,5 100% 100% Ciliary dyskinesia, primary, 14, CDKN1C 46,3 95% 80% Beckwith-Wiedemann syndrome, IMAGE syndrome, CEP ,1 100% 98%?Bardet-Biedl syndrome 14, Joubert syndrome 5, Leber congenital amaurosis 10, Meckel syndrome 4, Senior-Loken syndrome 6, CHD7 127,8 99% 99% CHARGE syndrome, {Scoliosis, idiopathic 3}, Hypogonadotropic hypogonadism 5 with or without anosmia, CITED2 107,4 100% 98% Ventricular septal defect 2, Atrial septal defect 8, CNTF 158,4 100% 100% No OMIM phenotype CNTRL 115,7 100% 99% No OMIM phenotype COL3A1 75,8 97% 93% Ehlers-Danlos syndrome,type III, Ehlers-Danlos syndrome, type IV, COL4A1 90,1 99% 97% Porencephaly 1, COL5A1 107,1 98% 96% Ehlers-Danlos syndrome, classic type I, COL5A2 91,3 99% 93% Ehlers-Danlos syndrome, classic type I, CRELD1 96,5 100% 98% {Atrioventricular septal defect, susceptibility to, 2}, Atrioventricular septal defect, partial, with heterotaxy syndrome,

5 CRKL 163,9 100% 100% No OMIM phenotype CRYAB 159,2 100% 100% Myopathy, myofibrillar, 2, Cataract 16, multiple types, Myopathy, myofibrillar, fatal infantile hypertrophy, alpha-b crystallin-related, Cardiomyopathy, dilated, 1II, CSRP3 123,1 100% 100% Cardiomyopathy, dilated, 1M, Cardiomyopathy, familial hypertrophic, 12, CTBP2 82,4 86% 77% No OMIM phenotype CTF1 18,3 37% 27% No OMIM phenotype CTLA4 119,4 100% 100% Autoimmune lymphoproliferative syndrome,type V, {Celiac disease,susceptibility to,3}, {Diabetes mellitus,insulin-dependent,12}, {Hashimoto thyroiditis}, {Systemic lupus erythematosus,susceptibility to}, CTNNA3 115,9 99% 97% Arrhytmogenic right ventricular dysplasia, familial, 13, CXADR 36,9 70% 61% No OMIM phenotype CXCR4 225,3 100% 100% WHIM syndrome, CYP11B2 105,8 98% 96% Hypoaldosteronism, congenital, due to CMO II deficiency, Hypoaldosteronism, congenital, due to CMO I deficiency, Low renin hypertension, susceptibility to Aldosterone to renin ratio raised DAW1 127,2 98% 94% No OMIM phenotype DCTN5 109,6 95% 93% No OMIM phenotype DDX39B 13,4 57% 22% No OMIM phenotype DES 109,7 96% 89% Arrhytmogenic right ventricular dysplasia, familial, 13, DMD 60 99% 96% Duchenne muscular dystrophy, Becker muscular dystrophy, Cardiomyopathy, dilated, 3B, DNAAF3 71,8 96% 77% Ciliary dyskinesia, primary, 2, DNAH11 123,9 100% 99% Ciliary dyskinesia, primary, 7, with or without situs inversus, DNAH5 101,1 99% 98% Ciliary dyskinesia, primary, 3, with or without situs inversus, DNAI1 134,8 100% 100% Ciliary dyskinesia, primary, 1, with or without situs inversus,

6 DNAJC19 67,2 78% 78% 3-methylglutaconic aciduria, type V, DNM2 85,3 100% 98% Charcot-Marie-Tooth disease, dominant intermediate B, Myopathy, centronuclear, Charcot-Marie-Tooth disease, axonal, type 2M, DOLK % 100% Congenital disorder of glycosylation, type Im, DPP6 110,8 94% 90% Mental retardation, autosomal dominant 33, {Ventricular fibrillation, paroxysmal familial, 2} DRC1 79,7 99% 97% Ciliary dyskinesia, primary, 21, DSC2 110,4 100% 100% Arrhythmogenic right ventricular dysplasia 11 without/with mild palmoplantar keratoderma and woolly hair, DSG2 137,7 100% 100% Arrhythmogenic right ventricular dysplasia 10, Cardiomyopathy, dilated, 1BB, DSP % 98% Arrhythmogenic right ventricular dysplasia 8, Cardiomyopathy, dilated, with woolly hair and keratoderma, Dilated cardiomyopathy with woolly hair, keratoderma and tooth agenesis, Epidermolysis bullosa,lethal acantholytic, Keratosis palmoplantaris striata II, Skin fragility-woolly hair syndrome, DTNA 104,2 99% 98% Left ventricular noncompaction 1, with or without congenital heart defects, DYNC2H1 119,8 99% 99% Short-rib thoracic dysplasia 3 with or without polydactyly, DYX1C1 87,8 100% 100% Ciliary dyskinesia, primary, 25, {Dyslexia, susceptibility to, 1}, EDN1 135,5 100% 100% auriculocondylar syndrome 3, Question mark ears,isolated, {High density lipoprotein cholesterol level QTL 7} EDNRA 119,6 100% 100% mandibulofacial dysostosis with alopecia, {Migraine, resistance to}, EDNRB 157,7 100% 99%?{Hirschsprung disease, susceptibility to}, ABCD syndrome, Waardenburg syndrome, type 4A, EFEMP2 112,8 100% 100% Cutis laxa,autosomal recessive,type IB, ELN 75,7 99% 97% Cutis laxa AD, Supravalvar aortic stenosis, EMD 92,6 100% 93% Emery-Dreifuss muscular dystrophy 1, X-linked,

7 ETS1 99,4 100% 99% No OMIM phenotype EYA4 132,5 100% 100% Deafness, autosomal dominant 10, Cardiomyopathy, dilated, 1J, FBN1 105,1 100% 99% Marfan syndrome, Ectopia lentis, familial, MASS syndrome, Weill-Marchesani syndrome 2, dominant, Aortic aneurysm, ascending, and dissection Stiff skin syndrome, Acromicric dysplasia, Geleophysic dysplasia 2, FBN2 111,4 99% 99% Contractural arachnodactyly, congenital, FHL1 38,9 96% 82% Scapuloperoneal myopathy, X-linked dominant, Myopathy, X-linked, with postural muscle atrophy, Myopathy, reducing body, X-linked, severe early-onset, Myopathy, reducing body, X-linked, childhood-onset, Emery-Dreifuss muscular dystrophy 6, X-linked, FHL2 110,2 100% 100% No OMIM phenotype FKTN 111,9 100% 100% Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4, Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4, Cardiomyopathy, dilated, 1X, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4, FLNA 65,7 99% 93% Heterotopia, periventricular, Otopalatodigital syndrome, type I, Otopalatodigital syndrome, type II, Intestinal pseudoobstruction, neuronal, Melnick-Needles syndrome, Frontometaphyseal dysplasia, Heterotopia, periventricular, ED variant, FG syndrome 2, Cardiac valvular dysplasia, X-linked, Terminal osseous dysplasia, Congenital short bowel syndrome,

8 FLNC % 95% Myopathy, myofibrillar, 5, Myopathy, distal, 4, FOXC2 92,2 99% 92% Lymphedema-distichiasis syndrome with/without renal disease and diabetes mellitus, FOXH1 61,6 99% 88% No OMIM phenotype FOXJ1 86,5 100% 100% No OMIM phenotype FOXL1 153,9 100% 96% No OMIM phenotype FREM2 139,8 99% 99% Fraser syndrome, FUZ 87,2 100% 98% Neural tube defects, FXN 102,9 93% 88% Friedreich ataxia, Friedreich ataxia with retained reflexes, GAA 109,1 100% 99% Glycogen storage disease II, GATA4 51,8 81% 65%?Testicular anomalies with or without congenital heart disease, Atrial septal defect 2, Atrioventricular septal defect 4, Tetralogy of Fallot, Ventricular septal defect 1, GATA5 56,5 97% 84% No OMIM phenotype GATA6 59,1 91% 80% Atrioventricular septal defect 5, Atrial septal defect 9, Pancreatic agenesis and congenital heart defects, Persistent truncus arteriosus, Tetralogy of Fallot, GATAD1 75,6 98% 91% Cardiomyopathy, dilated, 2B,

9 GDF1 30,9 93% 69% Double-outlet right ventricle, Tetralogy of Fallot, Transposition of great arteries, dextro-looped 3, Right atrial isomerism, GJA1 60,1 92% 83% Atrioventricular septal defect 3, Craniometaphyseal dysplasia, autosomal recessive, Erythrokeratodermia variabilis et progressiva, Hypoplastic left heart syndrome 1, Oculodentodigital dysplasia, Oculodentodigital dysplasia,autosomal recessive, Palmoplantar keratoderma with congenital alopecia, Syndactyly, type III, GJA5 79,4 100% 100% Atrial fibrillation, familial, 11, Atrial standstill, digenic, GJC % 100% No OMIM phenotype GLA 55,1 99% 82% Fabry disease, Fabry disease, cardiac variant, GPD1L 109,8 100% 100% Brugada syndrome 2, GTPBP3 96,6 100% 99% Combined oxidative phosphorylation deficiency 23 HAND1 115,2 100% 97% No OMIM phenotype HAND2 102,4 100% 100% No OMIM phenotype HCN1 103,3 100% 99% Epileptic encephalopathy,early infantile,24, HCN4 74,4 100% 98% Sick sinus syndrome 2, Brugada syndrome 8, HECTD1 136,7 100% 99% No OMIM phenotype HEY2 168,7 100% 100% No OMIM phenotype HFE % 97% Hemochromatosis, {Microvascular complications of diabetes 7}, {Porphyria variegata, susceptibility to}, {Porphyria cutanea tarda, susceptibility to}, {Alzheimer disease, susceptibility to}, [Transferrin serum level QTL2], HFE2 112,8 99% 95% Hemochromatosis type 2A, HOOK1 101,6 100% 97% No OMIM phenotype

10 HRAS 111,1 100% 100% {Bladder cancer, somatic}, Costello syndrome, {Thyroid carcinoma, follicular, somatic}, Congenital myopathy with excess of muscle spindles, {Nevus sebaceous, somatic}, Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic, IDUA 93,8 96% 88% Mucopolysaccharidosis Ih, Mucopolysaccharidosis Is, Mucopolysaccharidosis Ih/s, IFNG 124,9 99% 94% {AIDS,rapid progression of}, {Aplastic anemia}, {Hepatitis C virus,response to therapy of}, {TSC2 angiomyolipomas,renal,modifier of}, {Tuberculosis,protection against}, IFT140 93,6 99% 91% Mainzer-Saldino syndrome, IFT74 107,4 100% 100% No OMIM phenotype IL10 93,9 100% 100% {Graft-versus-host disease,protection against}, {HIV-1,susceptibility to}, {Rheumatoid arthritis,progression of}, ILK 150,3 100% 100% No OMIM phenotype IRX4 67,5 97% 92% No OMIM phenotype JAG1 110,5 97% 96% Alagille syndrome, JPH2 72,9 99% 98% Cardiomyopathy, familial hypertrophic 17, JUP 63,4 84% 73% Arrhythmogenic right ventricular dysplasia 12, Naxos disease, KCNA % 99% Atrial fibrillation, familial, 7, KCND2 153,4 100% 100% No OMIM phenotype KCND3 129,3 98% 96% Spinocerebellar ataxia 19, KCNE1 232,3 100% 100% Jervell and Lange-Nielsen syndrome 2, Long QT syndrome-5, KCNE2 146,4 100% 100% Long QT syndrome-6, Atrial fibrillation, familial, 4, KCNE3 99,2 100% 100% Brugada syndrome 6, KCNE4 77,4 80% 80% No OMIM phenotype

11 KCNH2 68,7 98% 92% Long QT syndrome-2, {Long QT syndrome-2, acquired, susceptibility to}, Short QT syndrome-1, KCNJ % 100% Hyperinsulinemic hypoglycemia, familial, 2, Diabetes, permanent neonatal, Diabetes mellitus, permanent neonatal, with neurologic features, {Diabetes mellitus, type 2, susceptibility to}, Diabetes mellitus, transient neonatal, 3, KCNJ12 343,1 100% 100% No OMIM phenotype KCNJ % 93% Andersen syndrome, Short QT syndrome-3, Atrial fibrillation, familial, 9, KCNJ % 100% No OMIM phenotype KCNJ5 192,5 100% 99% Long QT syndrome 13, Hyperaldosteronism, familial, type III, KCNJ8 162,6 100% 100% No OMIM phenotype KCNMB1 90,5 100% 97% {Hypertension,diastolic,resistance to}, KCNQ % 85% Long QT syndrome-1, Jervell and Lange-Nielsen syndrome, Atrial fibrillation, familial, 3, Short QT syndrome-2, {Long QT syndrome 1, acquired, susceptibility to}, KCNQ2 77,6 98% 95% Seizures, benign neonatal, 1, Myokymia, Epileptic encephalopathy, early infantile, 7, KIF7 80,4 94% 89% Hydrolethalus syndrome 2, KMT2D 111,8 99% 98% Kabuki syndrome 1,

12 KRAS 70,7 97% 92% Noonan syndrome 3, Bladder cancer, somatic, Breast cancer, somatic, Cardiofaciocutaneous syndrome 2, Gastric cancer, somatic, Lung cancer, somatic, Pancreatic carcinoma, somatic, SFM syndrome, somatic mosaic, LAMA4 109,7 100% 99% Cardiomyopathy, dilated, 1JJ, LAMP2 60,5 95% 88% Danon disease, LDB3 92,1 94% 92% Myopathy, myofibrillar, 4, Cardiomyopathy, dilated 1C, Left ventricular noncompaction 3, with or without dilated cardiomyopathy, LEFTY2 65,2 87% 64% Left-right axis malformations (Koasaki (1999) Am J Hum Genet 64, 712) LIMS1 33,7 20% 17% No OMIM phenotype LMNA 79,1 94% 88% Cardiomyopathy,dilated,1A, Charcot-Marie-Tooth disease,type 2B1, Emery-Dreifuss muscular dystrophy 2,AD, Emery-Dreifuss muscular dystrophy 3,AR, Heart-hand syndrome,slovenian type, Hutchinson-Gilford progeria, Lipodystrophy,familial partial,2, Malouf syndrome, Mandibuloacral dysplasia, Muscular dystrophy,congenital, Muscular dystrophy,limb-girdle,type 1B, Restrictive dermopathy,lethal, LOX 111,9 100% 100% No OMIM phenotype LRP1 115,4 98% 96% No OMIM phenotype LRP2 115,6 100% 99% Donnai-Barrow syndrome, LRP6 112,4 99% 98% {Coronary artery disease,autosomal dominant, 2}, LRRC10 112,1 100% 100% No OMIM phenotype LTBP1 108,2 99% 99% No OMIM phenotype MAP2K % 85% Cardiofaciocutaneous syndrome 3,

13 MAP2K2 114,9 100% 95% Cardiofaciocutaneous syndrome 4, MCTP2 113,7 100% 99% No OMIM phenotype MED13L 125,5 100% 99% Transposition of the great arteries, dextro-looped 1, MEF2C 106,8 100% 99% Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, Chromosome 5q14.3 deletion syndrome, MEGF8 96,4 99% 95% Carpenter syndrome 2, MIB1 117,2 100% 100% Left ventricular noncompaction 7, MICA 12,8 40% 29% No OMIM phenotype MICB 9,7 41% 14% No OMIM phenotype MMP21 146,2 98% 94% No OMIM phenotype MRPL % 89% Combined oxidative phosphorylation deficiency 9, MTO1 133,5 99% 94% Combined oxidative phosphorylation deficiency 10, MYBPC3 100,7 97% 95% Cardiomyopathy, familial hypertrophic, 4, Cardiomyopathy, dilated, 1MM, Left ventricular noncompaction 10, MYH10 120,4 100% 100% No OMIM phenotype MYH11 118,9 99% 97% Aortic aneurysm, familial thoracic 4, MYH6 105,5 97% 92% Cardiomyopathy, familial hypertrophic, 14, Atrial septal defect 3, Cardiomyopathy, dilated, 1EE, {Sick sinus syndrome 3}, MYH7 102,2 96% 89% Cardiomyopathy, familial hypertrophic, 1, Cardiomyopathy, dilated, 1S, Myopathy, myosin storage, Laing distal myopathy, Scapuloperoneal syndrome, myopathic type, Left ventricular noncompaction 5, MYH7B 75,9 98% 92% No OMIM phenotype MYL2 109,1 100% 100% Cardiomyopathy, familial hypertrophic, 10, MYL3 99,4 100% 99% Cardiomyopathy, familial hypertrophic, 8, MYL % 97% No OMIM phenotype MYLK 111,1 99% 96% Aortic aneurysm, familial thoracic 7, MYLK2 99,3 98% 96% Cardiomyopathy, hypertrophic, midventricular, digenic,

14 MYO1C 92 96% 91% No OMIM phenotype MYOM2 86,6 98% 95% No OMIM phenotype MYOT 140,5 100% 100% Muscular dystrophy, limb-girdle, type 1A, Myopathy, myofibrillar, 3, Myopathy, spheroid body, MYOZ % 100% No OMIM phenotype MYOZ2 104,1 100% 100% Cardiomyopathy, familial hypertrophic, 16, MYPN 122,2 99% 99% Cardiomyopathy, dilated, 1KK, Cardiomypathy, familial hypertrophic, 22, Cardiomyopaty, familial restrictive 4, MYZAP 108,5 100% 99% No OMIM phenotype NAT8 204,6 100% 100% No OMIM phenotype NDST1 120,2 100% 100% Mental retardation,autosomal recessive 46, NEBL 109,4 99% 96% No OMIM phenotype NEK8 121,9 100% 100%?Nephronophthisis 9,613824?Renal-hepatic-pancreatic dysplasia 2, NEXN 132,2 98% 98% Cardiomyopathy, dilated, 1CC, Cardiomyopathy, familial hypertrophic, 20, NFATC1 113,6 100% 100% No OMIM phenotype NFATC4 104,4 97% 94% No OMIM phenotype NFKBIL % 11% {Rheumatoid arthritis,susceptibility to}, NGF % 100% Neuropathy, hereditary sensory and autonomic, type V, NKX ,5 100% 99% Atrial septal defect 7, with or without AV conduction defects, NKX2-6 95,3 100% 92% Persistent truncus arteriosus, NODAL 135,7 93% 85% Heterotaxy, visceral, 5, NOS1AP 107,6 100% 99% No OMIM phenotype NOS3 85,4 92% 86% {Alzheimer disease,late-onset,susceptibility to}, {Coronary artery spasm 1,susceptibility to} {Hypertension,pregnancy-induced}, {Hypertension,susceptibility to}, {Ischemic stroke,susceptibility to}, {Placental abruption} NOTCH1 74,4 99% 92% Aortic valve disease, Adams-Oliver syndrome 5,616028

15 NOTCH % 88% Alagille syndrome 2, Hajdu-Cheney syndrome, NPPA 175,6 100% 100% Atrial fibrillation, familial, 6, NPPB 101,5 100% 97% No OMIM phenotype NR2F2 220,4 100% 100% Congenital heart defects,multiple types,4, NRAS 139,3 100% 100% Autoimmune lymphoproliferative syndrome type IV, Noonan syndrome 6, Epidermal nevus, somatic, Thyroid carcinoma, follicular, somatic, Colorectal cancer, somatic, NSD1 131,6 100% 99% Sotos syndrome 1, Leukemia, acute myeloid, (1) Beckwith-Wiedemann syndrome, OBSCN 91 98% 95% No OMIM phenotype PAFAH1B % 82% Lissencephaly, Subcortical laminar heterotopia, PCSK5 103,5 99% 98% No OMIM phenotype PDE2A 85,3 99% 95% No OMIM phenotype PDLIM3 120,5 100% 100% No OMIM phenotype PITX % 91% Axenfeld-Rieger syndrome type 1, Iridogoniodysgenesis,type 2, Peters anomaly, Ring dermoid of cornea, PKD % 18% Polycystic kidney disease, adult type I, PKD1L1 88,2 99% 96% No OMIM phenotype PKP2 75,1 88% 80% Arrhythmogenic right ventricular dysplasia 9, PKP4 106,3 99% 94% No OMIM phenotype PLA2G7 119,4 100% 100% Platelet-activating factor acetylhydrolase deficiency, Asthma, susceptibility to, Atopy, susceptibility to,

16 PLEC 111,7 99% 97%?Epidermolysis bullosa simplex with nail dystrophy, Epidermolysis bullosa simples with muscular dystrophy, Epidermolysis bullosa simplex with pyloric atresia, Epidermolysis bullosa simplex, Ogna type, Muscular dystrophy,limb-girdle,type 2Q, PLN 159,5 100% 100% Cardiomyopathy, dilated, 1P, Cardiomyopathy, familial hypertrophic, 18, PLXND1 78,6 96% 91% No OMIM phenotype PNN 127,4 100% 100% No OMIM phenotype PPARGC1A 126,8 100% 99% No OMIM phenotype PRDM1 178,6 100% 98% No OMIM phenotype PRDM16 120,8 99% 96% Left ventricular noncompaction 8, Cardiomyopathy, dilated, 1LL, PRICKLE1 114,1 100% 99% Epilepsy, progressive myoclonic 1B, PRKAG2 91,2 100% 100% Wolff-Parkinson-White syndrome, Cardiomyopathy, familial hypertrophic 6, Glycogen storage disease of heart, lethal congenital, PRKG1 100,4 100% 98% Aortic aneurysm, familial thoracic 8, PSKH1 126,7 100% 100% No OMIM phenotype PTK7 95,4 100% 98% No OMIM phenotype PTPLA 94,6 79% 73% No OMIM phenotype PTPN11 47,6 87% 70% Noonan syndrome 1, LEOPARD syndrome 1, Leukemia, juvenile myelomonocytic, Metachondromatosis, PTPN22 117,7 100% 100% {Diabetes,type 1,susceptibility to}, {Rheumatoid arthritis,susceptibility to}, {Systemic lupus erythematosus susceptibility to}, PTPRC 115,8 99% 96% {Hepatitic C virus, susceptibility to}, PTPRM 115,3 100% 99% No OMIM phenotype RAF1 97,2 100% 100% Noonan syndrome 5, LEOPARD syndrome 2, RANGRF % 96% No OMIM phenotype RBM20 114,2 100% 96% Cardiomyopathy, dilated, 1DD,

17 RIT1 136,7 100% 100% Noonan syndrome 8, ROBO1 130,8 99% 98% No OMIM phenotype ROBO2 114,6 100% 100% Vesicoureteral reflux 2, RPSA 23,5 83% 53% Asplenia, isolated congenital, RYR2 118,7 99% 99% Ventricular tachycardia, catecholaminergic polymorphic, 1, Arrhythmogenic right ventricular dysplasia 2, SCN10A 128,4 99% 98% Episodic pain syndrome,familial 2, SCN1B 121,8 99% 96% Atrial fibrillation,familial,13, Brugada syndrome 5, Cardiac conduction defect,nonspecific, Epilepsy, generalized, with febrile seizures plus, type 1, SCN2B 116,1 100% 97% Atrial fibrillation, familial, 14, SCN3B 100,9 100% 100% Brugada syndrome 7, SCN4B 88,5 100% 98% Long QT syndrome-10, SCN5A 117,5 100% 99% Long QT syndrome-3, Brugada syndrome 1, Heart block, progressive, type IA, Heart block, nonprogressive, Ventricular fibrillation, familial, 1, Sick sinus syndrome 1, Cardiomyopathy, dilated, 1E, {Sudden infant death syndrome, susceptibility to}, Atrial fibrillation, familial, 10, SCNN1B 93,9 100% 98% Bronchiectasis with or without elevated sweat chloride 1, Liddle syndrome, Pseudohypoaldosteronism,type I, SCNN1G 150,5 100% 100% Bronchiectasis with or without elevated sweat chloride 3, Liddle syndrome, Pseudohypoaldosteronism, type I, SCO % 100% Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, Myopia 6, SEMA3D 132,7 100% 100% No OMIM phenotype SGCA 99,2 92% 85% Muscular dystrophy, limb-girdle, type 2D,

18 SGCB 129,5 99% 96% Muscular dystrophy, limb-girdle, type 2E, SGCD 105,4 100% 100% Muscular dystrophy, limb-girdle, type 2F, Cardiomyopathy, dilated, 1L, SGCE 89,5 95% 94% maternally imprinted Dystonia-11, myoclonic, SGCG % 100% Muscular dystrophy, limb-girdle, type 2C, SHOC2 124,2 100% 100% Noonan-like syndrome with loose anagen hair, SHROOM3 119,1 100% 99% No OMIM phenotype SKI 69,8 88% 82% Shprintzen-Goldberg syndrome, SLC22A5 130,8 100% 99% Carnitine deficiency, systemic primary, SLC25A4 123,7 100% 99% Progressive external ophthalmoplegia with mitochondrial DNA deletions 3, Mitochondrial DNA depletion syndrome 12 (cardiomyopathic type), SLC2A10 103,3 99% 99% Arterial tortuosity syndrome, SLC8A1 121,8 99% 99% No OMIM phenotype SLMAP 130,5 100% 100% No OMIM phenotype SMAD2 151,7 100% 100% No OMIM phenotype SMAD3 83,8 88% 79% Loeys-Dietz syndrome type 3, SMAD6 84,8 98% 80% Aortic valve disease 2, SMARCA4 90,2 99% 95% Rhabdoid tumor predisposition syndrome 2, Mental retardation, autosomal dominant 16, SMYD1 87,6 100% 95% No OMIM phenotype SNTA1 61,1 99% 84% Long QT syndrome 12 SNTB1 108,7 100% 100% No OMIM phenotype SNX17 137,4 100% 100% No OMIM phenotype SOD2 182,9 97% 97% {Microvascular complications of diabetes 6}, SOS1 119,2 100% 100% Fibromatosis, gingival, Noonan syndrome 4, SUFU % 92% Medulloblastoma desmoplastic, Basal cell nevus syndrome, {Meningioma,familial,susceptibility to}, SYNE1 118,1 99% 97% Emery-Dreifuss muscular dystrophy 4, autosomal dominant, Spinocerebellar ataxia, autosomal recessive 8, SYNE2 110,7 97% 96% Emery-Dreifuss muscular dystrophy 5, autosomal dominant, SYNPO2 169,3 100% 99% No OMIM phenotype

19 TAB % 99% No OMIM phenotype TAB2 152,9 100% 97% Congenital heart defects, nonsyndromic, 2, TAZ 53,8 100% 98% Barth syndrome, TBC1D32 118,2 100% 100% No OMIM phenotype TBX1 80,9 82% 71% Conotruncal anomaly face syndrome, TBX20 53,9 71% 64% Atrial septal defect 4, TBX3 83,9 97% 91% Ulnar-mammary syndrome, TBX5 98,2 100% 97% Holt-Oram syndrome, TCAP 43,6 81% 58% Muscular dystrophy, limb-girdle, type 2G, Cardiomyopathy, dilated, 1N, TDGF1 74,5 100% 95% Forebrain defects Forebrain defects (de la Cruz (2002) Hum Genet 110, 422) Congenital heart defects (Roessler (2008) Am J Hum Genet 83, 18) TFAP2B 118,7 100% 100% Char syndrome, TGFB % 94% Camurati-Engelmann disease, {Cystic fibrosis lung disease, modifier of}, TGFB2 133,7 100% 98% Loeys-Dietz syndrome type 4, TGFB3 114,8 100% 99% Arrhythmogenic right ventricular dysplasia 1, TGFBR1 137,2 95% 93% Loeys-Dietz syndrome, type 1A, Loeys-Dietz syndrome, type 2A, {Multiple self-healing squamous epithelioma, susceptiblity to}, TGFBR2 97,6 100% 100% Colorectal cancer, hereditary nonpolyposis, type 6, Esophageal cancer, somatic, Loeys-Dietz syndrome, type 1B, Loeys-Dietz syndrome, type 2B, TLL % 100% Atrial septal defect 6, TMEM43 81,8 100% 99% Arrhythmogenic right ventricular dysplasia 5, Emery-Dreifuss muscular dystrophy 7, AD, TMEM67 121,8 100% 98% COACH syndrome, Joubert syndrome 6, Meckel syndrome 3, Nephronophthisis 11, {Bardet-Biedl syndrome 14,modifier of}, TMOD1 66,5 100% 97% No OMIM phenotype

20 TMPO 111,1 100% 97%?Cardiomyopathy,dilated,1T, TNF 18,2 78% 30% {Asthma,susceptibility to}, {Dementia,vascular,susceptibility to} {Malaria,cerebral, susceptibility to}, {Migraine without aura,susceptibility to}, {Septic shock,susceptibility to} TNNC1 112,1 100% 100% Cardiomyopathy, dilated, 1Z, Cardiomyopathy, familial hypertrophic, 13, TNNI % 93% Cardiomyopathy, familial hypertrophic, 7, Cardiomyopathy, familial restrictive, Cardiomyopathy, dilated, 2A, Cardiomyopathy, dilated, 1FF, TNNI3K 127,7 100% 100%?Cardiac conduction disease with/without dilated cardiomyopathy, TNNT2 108,7 100% 93% Cardiomyopathy, familial hypertrophic, 2, Cardiomyopathy, dilated, 1D, Cardiomyopathy, familial restrictive, 3, Left ventricular noncompaction 6, TPM1 100,6 100% 99% Cardiomyopathy, familial hypertrophic, 3, Cardiomyopathy, dilated, 1Y, Left ventricular noncompaction 9, TRDN 84,7 98% 95% Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness, TRIM63 109,1 100% 100% No OMIM phenotype TRPM4 91,8 100% 99% Progressive familial heart block, type IB, TTN 154,7 98% 97% Cardiomyopathy, familial hypertrophic, 9, Cardiomyopathy, dilated, 1G, Tibial muscular dystrophy, tardive, Muscular dystrophy, limb-girdle, type 2J, Myopathy, proximal, with early respiratory muscle involvement TTR 91,4 100% 99% Amyloidosis,hereditary,transthyretin-related, Carpal tunnel syndrome,familial, [Dystransthyretinemic hyperthyroxinemia], VCL 112,3 97% 94% Cardiomyopathy, dilated, 1W, Cardiomyopathy, familial hypertrophic, 15,

21 XIRP2 161,4 98% 98% No OMIM phenotype ZBTB14 186,7 100% 100% No OMIM phenotype ZBTB17 107,9 100% 97% No OMIM phenotype ZEB2 160,3 100% 100% Mowat-Wilson syndrome, ZFPM2 199,6 98% 98% Tetralogy of Fallot, Diaphragmatic hernia 3, ZIC3 60,1 100% 100% Heterotaxy, visceral, 1, X-linked Congenital heart defects, nonsyndromic, 1, X-linked, VACTERL association, X-linked, Gene symbols used follow HGCN guidelines Genomics 79(4): (2002) updated February 2014 Median Coverage describes the average number of reads seen across 50 exomes % Covered 10x describes the percentage of a gene s coding sequence that is covered at least 10x % Covered 20x describes the percentage of a gene s coding sequence that is covered at least 20x OMIM release used for OMIM disease identifiers and descriptions : June 30 th, 2015 This list is accurate for all panel versions starting with DG 2.3. (where x is a random number signifying a minor analysis patch without consequences for the panel composition or coverage information) Ad 1. No OMIM phenotype signifies a gene without a current OMIM association Ad 2. OMIM phenotype descriptions between {} signify risk factors