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  1. NGS Panel – Genetic Testing for Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy

May 12, 2017

Disease synonyms

Cardiomyopathy, familial hypertrophic, CMH, Ventricular hereditary hypertrophy, Asymmetric septal hypertrophy; ASH, Hypertrophic subaortic stenosis, Hereditary hypetrophic cardiomyopathy, HCM

Inheritance pattern

Autosomal dominant


Clinical features

Cardiomyopathies are disorders with primary abnormalities in the structure and function of the heart. These disorders are commonly grouped into morphological subtypes which include hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and left ventricular noncompaction cardiomyopathy (LVNC) 1.

Hypertrophic cardiomyopathy (HCM) is a global disease with cases reported in all continents, affecting people of both sexes and of various racial and ethnic origins. The incidence of HCM is approximately 1 in 500 in the general population2.

HCM is most commonly caused by pathogenic variants in one of the genes that encode different components of the sarcomere. The most common pathogenic mutations causing HCM were identified in genes encoding for the following: β-myosin heavy chain (MYH7, α-tropomyosin (TPM1), cardiac troponin T (TNNT2), cardiac myosin binding protein-C (MYBPC3), myosin regulatory light chain (MYL2), myosin essential light chain (MYL3), cardiac troponin I (TNNI3) and cardiac α-actin (ACTC1)5. Combined, MYBPC3 and MYH7 account for up to 50% of all clinically recognized cases of HCM, and constitute at least 75% of those affected where a mutation is identified2,5. Mutation of one of the genes that encodes a component of the sarcomere are found in approximately 50-60% of those affected with a family history of HCM, and 20-30% of those affected without a positive family history2, 3. Additional candidate genes, encoding proteins involved in cardiac muscle function, have been identified. CENTOGENE´s Cardiomyopathy hypertrophic panel includes the 36 genes most commonly associated with familial forms of HCM.

The clinical manifestations of HCM range from asymptomatic or progressive heart failure to sudden cardiac death (SCD). Clinical findings could significantly vary within the same family. Common symptoms include shortness of breath, chest pain, palpitations, orthostasis and syncope. Approximately 25% of persons affected with HCM show intracavitary obstruction at rest2. The degree of obstruction does not strictly correlate with the severity of symptoms or risk of sudden cardiac death. Patients affected with HCM are at an increased risk of atrial fibrillation (AF), which can have significant morbidity due to the increased risk of thromboembolism and symptomatic deterioration. The prevalence of AF increases with age. Furthermore, 5-10% of individuals with HCM progress to end-stage disease with impaired systolic function and, in some cases, left ventricular dilatation. The annual mortality rate in individuals with end-stage disease is estimated at 11% 4.

Treatment of HCM includes standard observation by a team of cardiologists, pharmacologic therapy, pacemakers or implantable cardiac defibrillators, and invasive septal reduction therapy. Cardiac transplantation may be necessary for patients with advanced refractory heart failure.

CENTOGENE offers sequencing of the genes in the CentoCardio™ panel(see Table 1).


Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
ABCC9 601439 Cantu syndrome/ Hypertrichotic osteochondrodysplasia; dilated cardiomyopathy-1O AD 18
ACTA2 102620 Aortic aneurysm, familial thoracic 6; Multisystemic smooth muscle dysfunction syndrome; Moyamoya disease 5 AD 5
ACTC1 102540 familial hypertrophic cardiomyopathy 11; Atrial septal defect 5; dilated cardiomyopathy-1R AD 1
ACTN2 102573 dilated cardiomyopathy-1AA AD 7
ACVR2B 602730 Heterotaxy, visceral, 4, autosomal 1
ACVRL1 601284 Telangiectasia, hereditary hemorrhagic, type 2 AD 4
AKAP9 604001 long QT syndrome 11 AD 12
ANK2 106410 long QT syndrome-4 AD 20
ANKRD1 609599 0
ARHGAP31 610911 Adams-Oliver syndrome 1 AD 12
ATM 607585 familial breast-ovarian cancer type 2; ataxia-telangiectasia AD, AR 82
B3GAT3 606374 Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects AR 5
BAG3 603883 Myopathy, myofibrillar, 6; dilated cardiomyopathy-1HH AD 3
BCOR 300485 Microphthalmia, syndromic 2 XLD 13
BMPR2 600799 Pulmonary hypertension, familial primary, 1, with or without HHT AD 2
BRAF 164757 Cardiofaciocutaneous Syndrome 1; Lung Cancer; Noonan syndrome 7; LEOPARD syndrome 3 AD 20
CACNA1C 114205 Timothy syndrome; Brugada syndrome 3; Long QT syndrome 8 AD 15
CACNB2 600003 Brugada syndrome 4 14
CALM1 114180 Ventricular tachycardia, catecholaminergic polymorphic, 4; Long QT syndrome 14 AD 0
CALM2 114182 Long QT syndrome 15 AD 0
CASQ2 114251 Ventricular tachycardia, catecholaminergic polymorphic, 2 AR 7
CAV3 601253 Creatine phosphokinase, elevated serum; familial hypertrophic cardiomyopathy 1; Rippling muscle disease; Rippling muscle disease 2; long QT syndrome 9 AD, DiD 8
CAVIN4 617714 2
CBL 165360 Leukemia, juvenile myelomonocytic; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia AD 9
CDH2 114020 AD 0
CFAP53 614759 Heterotaxy, visceral, 6, autosomal recessive AR 0
CFC1 605194 Heterotaxy, visceral, 2, autosomal AD 3
CHD7 608892 CHARGE syndrome; hypogonadotropic hypogonadism-5 with or without anosmia AD 103
CITED2 602937 Atrial septal defect 8 AD 1
CLDN16 603959 renal hypomagnesemia type 3 AR 1
CLDN19 610036 Hypomagnesemia 5, renal, with ocular involvement AR 3
CNNM2 607803 Hypomagnesemia 6, renal; hypomagnesemia, seizures, and mental retardation type 1 AD, AR 3
COL1A1 120150 Caffey disease; Ehlers-Danlos syndrome arthrochalasia type 1; osteogenesis imperfecta type 1; osteogenesis imperfecta type 2; osteogenesis imperfecta type 4; OSTEOPOROSIS; osteogenesis imperfecta type 3 AD 63
COL1A2 120160 osteogenesis imperfecta type 2; osteogenesis imperfecta type 4; OSTEOPOROSIS; Ehlers-Danlos syndrome, cardiac valvular form; osteogenesis imperfecta type 3; Ehlers-Danlos syndrome arthrochalasia type 2 AD, AR 52
COL3A1 120180 vascular-type Ehlers-Danlos syndrome AD, AR 31
COL4A1 120130 porencephaly 1; Brain small vessel disease with or without ocular anomalies; Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps; Hemorrhage, intracerebral, susceptibility to AD 71
COL4A2 120090 Brain small vessel disease type 2; Hemorrhage, intracerebral, susceptibility to AD 18
COL5A1 120215 Ehlers-Danlos syndrome classic type 1 AD 91
COL5A2 120190 Ehlers-Danlos syndrome classic type 2 AD 36
CREBBP 600140 Rubinstein-Taybi syndrome 1 AD 39
CRELD1 607170 Atrioventricular septal defect, partial, with heterotaxy syndrome AD 6
CRYAB 123590 Myopathy, myofibrillar, 2; Cataract 16, multiple types; Myopathy, Myofibrillar, Fatal Infantile Hypertonic, Alpha-B Crystallin-Related; dilated cardiomyopathy-1II AD, AR 1
CSRP3 600824 dilated cardiomyopathy-1M; Cardiomyopathy, familial hypertrophic, 12 AD 1
CTNNA3 607667 familial arrhythmogenic right ventricular dysplasia type 13 AD 2
DES 125660 Scapuloperoneal syndrome, neurogenic, Kaeser type; Myopathy, myofibrillar, 1; dilated cardiomyopathy-1I AD, AR 4
DMD 300377 Becker muscular dystrophy; dilated cardiomyopathy type 3B; Duchenne muscular dystrophy XL, XLR 688
DNAJC19 608977 3-methylglutaconic aciduria, type 5 AR 4
DOLK 610746 congenital disorder of glycosylation type 1m AR 2
DSC2 125645 Arrhythmogenic right ventricular dysplasia 11 AD, AR 13
DSG2 125671 Arrhythmogenic right ventricular dysplasia 10; dilated cardiomyopathy AD 11
DSP 125647 dilated cardiomyopathy with woolly hair and keratoderma; arrhythmogenic right ventricular dysplasia type 8; lethal acantholytic epidermolysis bullosa; Keratosis palmoplantaris striata II; dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis AD, AR 11
DTNA 601239 Left ventricular noncompaction 1, with or without congenital heart defects AD 1
EFEMP2 604633 Cutis laxa, autosomal recessive, type IB AR 2
EGF 131530 Hypomagnesemia 4, renal 0
EHMT1 607001 Kleefstra syndrome AD 24
ELN 130160 Cutis laxa, autosomal dominant 1, ADCL1; Supravalvar aortic stenosis AD 6
EMD 300384 Emery-Dreifuss muscular dystrophy type 1 XLR 8
ENG 131195 hereditary hemorrhagic telangiectasia type 1 AD 7
EP300 602700 colorectal cancer; Rubinstein-Taybi syndrome 2 AD 25
EVC 604831 Weyers acrofacial dysostosis; Ellis-van Creveld syndrome AD, AR 9
EVC2 607261 Weyers acrofacial dysostosis; Ellis-van Creveld syndrome AD, AR 5
EYA4 603550 Deafness, autosomal dominant 10; dilated cardiomyopathy-1J AD 10
FBN1 134797 Marfan syndrome; stiff skin syndrome; Weill-Marchesani syndrome 2; geleophysic dysplasia 2; Marfan lipodystrophy syndrome AD 76
FBN2 612570 congenital contractural arachnodactyly; early-onset macular degeneration AD 39
FHL1 300163 Scapuloperoneal myopathy, X-linked dominant; Myopathy, X-linked, with postural muscle atrophy; Emery-Dreifuss muscular dystrophy 6; Myopathy, Reducing Body, X-Linked, Early-Onset, Severe; Myopathy, reducing body, X-linked, childhood-onset XL, XLD, XLR 13
FKTN 607440 congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A4; congenital limb-girdle muscular dystrophy-dystroglycanopathy type C4; dilated cardiomyopathy type 1X; congenital muscular dystrophy-dystroglycanopathy without mental retardation type B4 AR 10
FLNA 300017 Congenital short bowel syndrome; Heterotopia, periventricular / X-linked periventricular heterotopia; Terminal osseous dysplasia; FG syndrome 2; Otopalatodigital syndrome, type II; Frontometaphyseal dysplasia; Melnick-Needles syndrome; otopalatodigital syndrome type I; Cardiac valvular dysplasia, X-linked XL, XLD, XLR 39
FLNC 102565 Myopathy, myofibrillar, 5; distal myopathy type 4; Cardiomyopathy, Familial Hypertrophic, 26 AD 10
FOXC1 601090 Iridogoniodysgenesis, type 1; Axenfeld-Rieger syndrome, type 3 AD 8
FOXF1 601089 Pulmonary hypertension, familial persistent, of the newborn AD 2
FOXH1 603621 3
FXYD2 601814 Hypomagnesemia-2, renal AD 2
GAA 606800 Pompe disease AR 130
GATA4 600576 Tetralogy of Fallot; Atrial septal defect 2; Ventricular septal defect 1; Atrioventricular septal defect 4 AD 2
GATA5 611496 Congenital heart defects, multiple types, 5 AD, AR 2
GATA6 601656 Tetralogy of Fallot; Conotruncal Heart Malformations; Pancreatic agenesis and congenital heart defects; Atrioventricular septal defect 5; Atrial septal defect 9 AD 2
GDF1 602880 Right atrial isomerism; Transposition of the great arteries, dextro-looped 3 AD, AR 5
GDF2 605120 Telangiectasia, hereditary, hemorragic, type 5 AD 0
GJA1 121014 Oculodentodigital dysplasia AD, AR 3
GJA5 121013 AD 0
GLA 300644 Fabry disease; Fabry disease, atypical cardiac variant XL 630
GPC3 300037 Wilms tumor, type 1; Simpson-Golabi-Behmel syndrome, type 1 XLR 7
GPD1L 611778 Brugada syndrome 2 3
HCCS 300056 Microphthalmia, syndromic 7 XLD 2
HCN4 605206 Sick sinus syndrome 2; Brugada syndrome 8 AD 3
HFE 613609 Alzheimer Disease; hepatoerythropoietic porphyria; variegate porphyria; hemochromatosis type 1; susceptibility to microvascular complications of diabetes type 7; Transferrin serum level QTL2 AD, AR 11
HRAS 190020 Bladder Cancer; Melanocytic nevus syndrome, congenital, somatic; Nevus, Epidermal; Schimmelpenning-Feuerstein-Mims Syndrome; Thyroid Carcinoma, Follicular; Costello syndrome AD 10
HTRA1 602194 Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy type 2 AD, AR 2
ILK 602366 0
JAG1 601920 Alagille syndrome; Tetralogy of Fallot AD 43
JPH2 605267 Cardiomyopathy, familial hypertrophic 17 AD 6
JUP 173325 Naxos disease; Arrhythmogenic right ventricular dysplasia 12 AD, AR 3
KCNA1 176260 Episodic ataxia/myokymia syndrome AD 7
KCNA5 176267 Atrial fibrillation, familial, 7 AD 1
KCND3 605411 spinocerebellar ataxia 19 AD 13
KCNE1 176261 Jervell and Lange-Nielsen syndrome 2; long QT syndrome 5 AD, AR 6
KCNE2 603796 long QT syndrome 6 AD 1
KCNE3 604433 Brugada syndrome 6 1
KCNH2 152427 long QT syndrome 2 AD 17
KCNJ2 600681 Andersen Cardiodysrhythmic Periodic Paralysis; Short Qt Syndrome 3; Atrial fibrillation, familial, 9 AD 2
KCNJ5 600734 Long QT syndrome 13 AD 3
KCNK3 603220 primary pulmonary hypertension AD 2
KCNQ1 607542 long QT syndrome-1; Jervell and Lange-Nielsen syndrome; Atrial fibrillation, familial, 3; Short QT syndrome-2 AD, AR 21
KDM6A 300128 Kabuki syndrome 2 XLD 12
KMT2D 602113 Kabuki syndrome 1 AD 53
KRAS 190070 Arteriovenous malformations of the brain; Bladder Cancer; familial breast-ovarian cancer type 2; Gastric Cancer, Hereditary Diffuse; Schimmelpenning-Feuerstein-Mims Syndrome; Lung Cancer; Pancreatic Cancer; acute myeloid leukemia; Noonan syndrome 3; Autoimmune lymphoproliferative syndrome type IV; Cardiofaciocutaneous syndrome 2 AD 9
LAMA4 600133 dilated cardiomyopathy-1JJ AD 1
LAMP2 309060 Danon disease XLD 12
LDB3 605906 dilated cardiomyopathy-1C; Myopathy, myofibrillar, 4 AD 8
LMNA 150330 dilated cardiomyopathy-1A; Lipodystrophy, familial partial, 2; Hutchinson-Gilford progeria; limb-girdle muscular dystrophy type 1B; Emery-Dreifuss muscular dystrophy 2; Malouf syndrome; Mandibuloacral dysplasia; Restrictive dermopathy, lethal; type 2B1 Charcot-Marie-Tooth disease; Heart-hand syndrome, Slovenian type; Muscular dystrophy, congenital; Emery-Dreifuss muscular dystrophy 3, AR AD, AR 20
LZTR1 600574 Noonan syndrome type 2; SCHWANNOMATOSIS 2; Noonan syndrome 10 AD, AR 19
MAP2K2 601263 Cardiofaciocutaneous syndrome 4 AD 8
MED12 300188 Opitz-Kaveggia syndrome /FG syndrome-1; Lujan-Fryns syndrome XLR 16
MED13L 608771 Mental retardation and distinctive facial features with or without cardiac defects AD 24
MEIS2 601740 Cleft palate, cardiac defects, and mental retardation AD 1
MFAP5 601103 AD 0
MIB1 608677 Left ventricular noncompaction 7 AD 2
MMP21 608416 Heterotaxy, visceral, 7, autosomal AR 5
MMP3 185250 Coronary heart disease, susceptibility to, 6 2
MYBPC3 600958 familial hypertrophic cardiomyopathy 4; dilated cardiomyopathy-1MM AD, AR 21
MYH11 160745 familial thoracic aortic aneurysm 4 AD 25
MYH6 160710 Cardiomyopathy, familial hypertrophic, 14; dilated cardiomyopathy-1EE; Atrial septal defect 3 AD 30
MYH7 160760 Liang distal myopathy; Scapuloperoneal syndrome, myopathic type; familial hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myopathy, myosin storage, autosomal dominant; dilated cardiomyopathy-1S AD, AR, DiD 40
MYL2 160781 Cardiomyopathy, familial hypertrophic, 10 AD 5
MYL3 160790 familial hypertrophic cardiomyopathy 8 AD, AR 2
MYLK 600922 Aortic aneurysm, familial thoracic 7 AD, AR 20
MYLK2 606566 familial hypertrophic cardiomyopathy 1 AD, DiD 4
MYO6 600970 deafness type 37 AD, AR 15
MYOZ2 605602 Cardiomyopathy, familial hypertrophic, 16 AD 3
MYPN 608517 dilated cardiomyopathy-1KK; Autosomal recessive Nemaline myopathy type 11 AD, AR 5
NEBL 605491 0
NEXN 613121 dilated cardiomyopathy-1CC; familial hypertrophic cardiomyopathy 20 AD 9
NF1 613113 neurofibromatosis type 1; Neurofibromatosis-Noonan syndrome; Leukemia, juvenile myelomonocytic AD 140
NIPBL 608667 Cornelia de Lange syndrome 1 AD 40
NKX2-5 600584 Atrial Septal Defect 7 With Or Without Atrioventricular Conduction Defects; Tetralogy of Fallot; Conotruncal Heart Malformations; Hypothyroidism, Congenital, Nongoitrous, 5; Ventricular septal defect 3; Hypoplastic left heart syndrome 2 AD 3
NKX2-6 611770 Conotruncal Heart Malformations 1
NODAL 601265 Heterotaxy, visceral, 5, autosomal AD 2
NOTCH1 190198 aortic valve disease type 1; Adams-Oliver syndrome 5 AD 12
NOTCH2 600275 Hajdu-Cheney syndrome; Alagille syndrome 2 AD 116
NOTCH3 600276 CADASIL; Lateral meningocele syndrome AD 55
NPPA 108780 Atrial standstill 2 AD, AR 0
NR2F2 107773 Congenital heart defects, multiple types, 4 AD 2
NRAS 164790 colorectal cancer; Melanocytic nevus syndrome, congenital, somatic; Nevus, Epidermal; Schimmelpenning-Feuerstein-Mims Syndrome; Thyroid Carcinoma, Follicular; Neurocutaneous melanosis, somatic; Noonan syndrome 6; Autoimmune lymphoproliferative syndrome type IV AD 5
NSD1 606681 Sotos syndrome 1 AD 40
PDLIM3 605889 0
PKD1L1 609721 Visceral heterotaxy type 8 AR 1
PKD2 173910 polycystic kidney disease type 2 AD 44
PKP2 602861 arrrhythmogenic right ventricular dysplasia 9 AD 5
PLN 172405 dilated cardiomyopathy-1P; Cardiomyopathy, familial hypertrophic, 18 AD 0
PRDM16 605557 left ventricular noncompaction 8 AD 2
PRKAG2 602743 Wolff-Parkinson-White syndrome; fatal congenital hypertrophic cardiomyopathy due to glycogen storage disease; familial hypertrophic cardiomyopathy 6 AD 19
PRKG1 176894 familial thoracic aortic aneurysm type 8 AD 1
PSEN1 104311 Pick disease; Dementia, frontotemporal; early-onset familial Alzheimer disease-3; dilated cardiomyopathy-1U; Acne inversa, familial, 3 AD 14
PSEN2 600759 Alzheimer disease, type 4; dilated cardiomyopathy-1V AD 20
PTPN11 176876 LEOPARD syndrome 1; Noonan syndrome 1; Leukemia, juvenile myelomonocytic AD 13
RAF1 164760 Noonan syndrome 5; Cardiomyopathy, dilated, 1NN AD 8
RASA1 139150 Capillary malformation-arteriovenous malformation AD 2
RBM10 300080 TARP syndrome XLR 3
RBM20 613171 dilated cardiomyopathy-1DD AD 5
RIT1 609591 Noonan syndrome 8 AD 2
RYR2 180902 Arrhythmogenic right ventricular dysplasia 2; Ventricular tachycardia, catecholaminergic polymorphic, 1 AD 26
SALL1 602218 Townes-Brocks syndrome AD 30
SALL4 607343 Okihiro syndrome AD 15
SCN10A 604427 familial episodic pain syndrome, 2 AD 3
SCN1B 600235 generalized epilepsy with febrile seizures plus-1; Brugada syndrome 5; Epileptic encephalopathy, early infantile, 52 AD, AR 5
SCN2B 601327 AD 0
SCN3B 608214 Brugada syndrome 7 AD 4
SCN4B 608256 Long Qt Syndrome 10 AD 2
SCN5A 600163 susceptibility to sudden infant death syndrome; Brugada syndrome 1; dilated cardiomyopathy-1E; long QT syndrome 3; Sick sinus syndrome 1; Familial atrial fibrillation type 10 AD, AR 27
SCO2 604272 Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1; Myopia 6 AD, AR 1
SDHA 600857 mitochondrial complex II deficiency; Leigh syndrome; dilated cardiomyopathy-1GG; paragangliomas type 5 AD, AR, M 33
SEMA3A 603961 hypogonadotropic hypogonadism 16 with or without anosmia AD 36
SGCD 601411 limb-girdle muscular dystrophy type 2F; dilated cardiomyopathy-1L AR 5
SHOC2 602775 Noonan Syndrome-Like Disorder With Loose Anagen Hair AD 6
SKI 164780 Shprintzen-Goldberg Craniosynostosis Syndrome AD 3
SLC12A3 600968 Gitelman syndrome AR 36
SLC22A5 603377 systemic primary carnitine deficiency AR 8
SLC25A4 103220 Progressive External Ophthalmoplegia With Mitochondrial Dna Deletions, Autosomal Dominant, 2; mitochondrial DNA depletion syndrome 12; mitochondrial DNA depletion syndrome type 12A AD, AR 11
SLC2A10 606145 arterial tortuosity syndrome AR 9
SLMAP 602701 5
SMAD3 603109 Loeys-Dietz syndrome 3 AD 6
SMAD4 600993 Myhre syndrome; Juvenile polyposis syndrome, infantile form; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome; Pancreatic Cancer AD 3
SMAD6 602931 Aortic valve disease 2; Craniosynostosis type 7 AD 4
SMC3 606062 Cornelia de Lange syndrome 3 AD 24
SNTA1 601017 long QT syndrome 12 AD 0
SOS1 182530 Noonan syndrome 4 AD 18
SOS2 601247 Noonan syndrome type 9 AD 4
SOX2 184429 Microphthalmia, Syndromic 3 AD 8
STRA6 610745 Microphthalmia, isolated, with coloboma 8 AR 12
SYNE1 608441 autosomal recessive spinocerebellar ataxia 8; Emery-Dreifuss muscular dystrophy 4 AD, AR 70
SYNE2 608442 Emery-Dreifuss muscular dystrophy 5 AD 15
TAB2 605101 Congenital heart defects, nonsyndromic, 2 AD 4
TAZ 300394 Barth syndrome XLR 6
TBX1 602054 Tetralogy of Fallot; DiGeorge syndrome; Velocardiofacial syndrome; Conotruncal Heart Malformations AD 11
TBX20 606061 Atrial septal defect 4 1
TBX5 601620 Holt-Oram syndrome AD 17
TCAP 604488 limb-girdle muscular dystrophy type 2G; cardiomyopathy, familial hypertrophic, 25 AD, AR 6
TFAP2B 601601 Char syndrome; Patent ductus arteriosus 2 AD 1
TGFB2 190220 Loeys-Dietz syndrome 4 AD 5
TGFB3 190230 Arrhythmogenic right ventricular dysplasia 1; Loeys-Dietz syndrome 5 AD 12
TGFBR1 190181 Multiple Self-Healing Squamous Epithelioma, Susceptibility To; Loeys-Dietz syndrome 1 AD 8
TGFBR2 190182 Esophageal cancer, somatic; Loeys-Dietz syndrome 2; Colorectal cancer, hereditary nonpolyposis, type 6 AD 5
TLL1 606742 Atrial septal defect 6 AD 0
TMEM43 612048 arrhythmogenic right ventricular dysplasia 5 AD 6
TNNC1 191040 dilated cardiomyopathy-1Z; familial hypertrophic cardiomyopathy 13 AD 2
TNNI3 191044 Cardiomyopathy, familial restrictive, 1; dilated cardiomyopathy-2A; familial hypertrophic cardiomyopathy 7 AD, AR 10
TNNT2 191045 familial hypertrophic cardiomyopathy 2; dilated cardiomyopathy-1D AD 20
TPM1 191010 Cardiomyopathy, familial hypertrophic, 3; dilated cardiomyopathy-1Y AD 20
TRDN 603283 catecholaminergic polymorphic ventricular tachycardia type 5 AR 3
TREX1 606609 systemic lupus erythematosus; retinal vasculopathy with cerebral leukodystrophy; Aicardi-Goutieres syndrome type 1; chilblain lupus type 1 AD, AR 12
TRIM63 606131 0
TRPM4 606936 AD 0
TRPM6 607009 Hypomagnesemia 1, intestinal AR 10
TTN 188840 Tibial muscular dystrophy, tardive; Hereditary myopathy with early respiratory failure; dilated cardiomyopathy type 1G; limb-girdle muscular dystrophy type 2J; early-onset myopathy with fatal cardiomyopathy; familial hypertrophic cardiomyopathy type 9 AD, AR 116
TTR 176300 familial transthyretin amyloidosis AD 22
VCL 193065 dilated cardiomyopathy-1W; Cardiomyopathy, familial hypertrophic, 15 AD 9
ZEB2 605802 Mowat-Wilson syndrome AD 47
ZFPM2 603693 Tetralogy of Fallot; Diaphragmatic hernia 3; 46XY sex reversal 9 AD 1
ZIC3 300265 Heterotaxy, visceral, 1, x-linked; Vacterl association, x-linked, with or without hydrocephalus XLR 1

Differential diagnosis

The differential diagnosis of hypertrophic cardiomyopathy related disorders – depending on the major symptoms in the initial case – includes the following diseases11, 2, 3:

  • Acquired left ventricular hypertrophy (LVH).
  • Aortic stenosis
  • Hypertensive heart disease
  • Syndromes with LVH (i.e., LVH associated with an underlying metabolic disorder or muscle disease including Fabry disease, cardiac amyloidosis, and Danon disease)
  • Childhood-onset conditions with LVH:

    • Inborn errors of metabolism
    • Malformation syndromes
    • Neuromuscular disorders


Testing strategy

CENTOGENE offers advanced, fast and cost-effective strategy to test large NGS panels and diagnose complex phenotypes based on the PCR-free Whole Genome Sequencing and NGS technology. This approach offers an unparalleled advantage by reducing amplification/capture biases and provides sequencing of entire gene at a more uniform coverage.

To confirm/establish the diagnosis, CENTOGENE offers the following testing strategy for cardiomyopathy hypertrophic using NGS Panel Genomic targeted towards this specific phenotype:

Step 1: Whole genome sequencing from a single filter card. The sequencing covers the entire genic region (coding region, exon/intron boundaries, intronic and promoter) for all the genes included in the Cardiomyopathy hypertrophic panel. Copy Number Variants analysis derived from NGS data is also included.

Step 2: If no mutation is identified after analysis of the Cardiomyopathy hypertrophic panel, based on the approval and consent, we further recommend to continue the bioinformatics analysis of the data obtained by whole genome sequencing to cover genes that are either implicated in an overlapping phenotype or could be involved in a similar pathway but not strongly clinically implicated based on the current information in literature.


Referral reasons

The following individuals are candidates for hypertrophic cardiomyopathy panel genetic testing:

  • Individuals with a family history of disease and presentation of the most common symptoms
  • Individuals without a positive family history, but with symptoms resembling this disease
  • Individuals with a negative but suspected family history, in order to perform proper genetic counseling (prenatal analyses are recommended in families with affected individuals).

Test utility

Sequencing, deletion/duplication of this gene and related genes should be performed in all individuals suspected for this particular phenotype. In parallel, other genes reported to be related with this clinical phenotype should also be analyzed for the presence of mutations, due to the overlap in many clinical features caused by those particular genes.

Confirmation of a clinical diagnosis through genetic testing can allow for genetic counseling and may direct medical management. Genetic counseling can provide a patient and/or family with the natural history of the condition, identify at-risk family members, provide reproductive risks as well as preconception/prenatal options, and allow for appropriate referral for patient support and/or resources.