Table 3.

Selected Genes in Association With Cardiomyopathy

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

Abbreviations as in Tables 1 and 2.

^*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.