Hypertrophic Cardiomyopathy Gene Curation

Cardiovascular Domain

Our group, the ClinGen HCM gene curation committee, subgroup of the ClinGen Cardiovascular Working Group, used the ClinGen gene:disease clinical validity framework to evaluate the strength of evidence for genes implicated in hypertrophic cardiomyopathy.

Each curation was performed for a gene:disease pair according to the ClinGen Gene Clinical Validity Curation Standard Operating Procedure (version 4.0).


ClinGen Gene:Disease Clinical Validity Classifications for genes implicated in Hypertrophic Cardiomyopathy

ClinGen Hypertrophic Cardiomyopathy Gene Curation Committee; ClinGen Cardiovascular Working Group

Version Date: October 16th, 2017

Gene                  Disease                                                                       Classification

CACNB2             Hypertrophic cardiomyopathy                                      No genetic evidence

TNNC2               Hypertrophic cardiomyopathy                                      No genetic evidence

DSP                     Hypertrophic cardiomyopathy                                     No genetic evidence

KCNQ1               Hypertrophic cardiomyopathy                                      No genetic evidence

TMPO                 Hypertrophic cardiomyopathy                                      No genetic evidence

ACTA1                Hypertrophic cardiomyopathy                                      No genetic evidence

CASQ2                Hypertrophic cardiomyopathy                                     No genetic evidence

CALR3                Hypertrophic cardiomyopathy                                      Limited

MYOM1               Hypertrophic cardiomyopathy                                     Limited             

TCAP                  Hypertrophic cardiomyopathy                                      Limited

OBSCN               Hypertrophic cardiomyopathy                                      Limited

TRIM63               Hypertrophic cardiomyopathy                                      Limited

VCL                     Hypertrophic cardiomyopathy                                      Limited

PDLIM3               Hypertrophic cardiomyopathy                                      Limited

MYLK2                Hypertrophic cardiomyopathy                                       Limited

NEXN                  Hypertrophic cardiomyopathy                                       Limited

MYPN                 Hypertrophic cardiomyopathy                                        Limited

KLF10                 Hypertrophic cardiomyopathy                                       Limited

MYOZ2               Hypertrophic cardiomyopathy                                        Limited

JPH2                   Hypertrophic cardiomyopathy                                        Moderate

TNNC1               Hypertrophic cardiomyopathy                                         Moderate

ALPK3                 Hypertrophic cardiomyopathy                                        Strong

ACTC1                Hypertrophic cardiomyopathy                                        Definitive

MYH7                 Hypertrophic cardiomyopathy                                        Definitive

MYBPC3            Hypertrophic cardiomyopathy                                         Definitive

MYL2                  Hypertrophic cardiomyopathy                                         Definitive

MYL3                  Hypertrophic cardiomyopathy                                         Definitive

TNNI3                Hypertrophic cardiomyopathy                                         Definitive

TNNT2               Hypertrophic cardiomyopathy                                         Definitive

TPM1                 Hypertrophic cardiomyopathy                                         Definitive

ACTN2**            Intrinsic cardiomyopathy*                                               Moderate

PLN                    Intrinsic cardiomyopathy*                                               Definitive


*Intrinsic cardiomyopathy is defined as a cardiomyopathy, not due to an identifiable external cause, that includes cardiac phenotypes in addition to hypertrophic cardiomyopathy, such as dilated cardiomyopathy, left ventricular non-compaction, and arrhythmia (see Ontology Lookup Service at https://www.ebi.ac.uk/ols/index ; DOID:0060036)

**Note: Much of the evidence for the moderate classification for ACTN2 came from segregation data in two large families.


Genes causing syndromes which include Hypertrophic Cardiomyopathy as part of the presentation.

Gene                  Disease                                                                   Classification

ABCC9                Cantu syndrome                                                      Definitive

BAG3                  Myofibrillar myopathy                                              Definitive

CACNA1C          Timothy syndrome                                                   Definitive

COX15                Cytochrome c oxidase deficiency                           Strong

CRYAB                Myofibrillar myopathy                                             Definitive

DES                     Myofibrillar myopathy                                             Definitive

FHL1                   Emery Dreifuss muscular dystrophy                       Definitive

FLNC                   Myofibrillar myopathy                                             Definitive

FXN                     Friedreich's ataxia                                                  Definitive

GAA                    Pompe disease                                                       Definitive

GLA                     Fabry disease                                                         Definitive

LAMP2               Danon disease                                                         Definitive

SLC25A4            Mitochondrial DNA depletion syndrome                  Definitive

TTR                     Amyloidosis                                                            Definitive


Genes that have been curated and await final approval: Hypertrophic Cardiomyopathy: ANKRD1, CSRP3, LDB3, MYH6, RYR2, TTN Syndromic: CAV3 - caveolinopathy

Curated by the ClinGen Hearing Loss Group: MYO6 - Hearing Loss and Hypertrophic Cardiomyopathy