Table 3.
Cardiomyopathy | Core Genes* | Estimates of Genetic Testing DiagnosticYield | ACMG Secondary Findings Gene List | Metabolic Causes of Cardiomyopathty | Examples of Genetic Syndromes |
---|---|---|---|---|---|
| |||||
HCM | MYH7, MYBPC3, TNNT2, TNNC1, TNNI3, TPM1, MYL2, MYL3, ACTC1, ACTN2, CSRP3, PLN, TTR, PRKAG2, LAMP2, GLA | 30%–60% | MYBPC3, MYH7, TNNT2, TNNI3, TPM1, MYL3, ACTC1, PRKAG2, GLA, MYL2, LMNA | GAA (Pompe); Mitochondrial disease genes | RASopathies (eg, Noonan syndrome, others); Friedreich ataxia |
DCM | TTN,† LMNA, MYH7, TNNT2, BAG3, RBM20, TNNC1, TNNI3, TPM1, SCN5A, PLN. For testing, all HCM and ARVC genes are recommended to be included. | 10%–40% | Mitochondrial disease genes | Muscular dystrophies; Alström syndrome | |
ARVC | DES, DSC2, DSG2, DSP, JUP, LMNA, PKP2, PLN, RYR2, SCN5A, TMEM43, TTN†; consider full DCM panel | 10%–50% | PKP2, DSP, DSC2, TMEM43, DSG2, RYR2 SCN5A | Naxos syndrome; Carvajal syndrome |
|
RCM | Consider HCM or DCM gene panel | 10%–60% | |||
LVNC | Use the gene panel for the cardiomyopathy identified in association with the LVNC phenotype | Unknown | Mitochondrial disease genes, including TAZ in Barth syndrome | 1p36 deletion syndrome; RASopathies |
Core gene lists represent genes with the highest diagnostic yield and/or strongest evidence of the gene in association with the listed phenotype; the genes listed are not exhaustive and should be considered as illustrative for the type of cardiomyopathy. Considerable overlap of genes between cardiomyopathy phenotypes is well established. Genes known to cause metabolic disease or genetic syndromes are often included in testing panels, but that varies depending on the clinical laboratory. Gene lists therefore need to be reviewed carefully before ordering testing. Metabolic and genetic syndrome columns provide examples only and are not intended to be comprehensive.
Only TTN truncating variants are thought to be relevant for cardiomyopathy.