Table 1.

Benefits and limitations of genetic testing in HCM

		Examples and Consequences	Future Implications
Benefits	Confirm diagnosis in ambiguous situations	An athlete with LVH and a pathogenic sarcomere mutation is advised to stop competitive sports due to sudden death risk A patient with mild LVH, hypertension, syncope, and a family history of sudden death is found to have a pathogenic sarcomere mutation, triggering family screening and ICD placement
	Definitive identification of at-risk family members	Longitudinal clinical screening is focused only on mutation carriers, reducing health care costs and unnecessary restrictions in mutation (−) relatives A patient with a severe mutation (early SCD and transplant in relatives) has reproductive choices, including preimplantation genetic diagnosis	Studying young mutation carriers without LVH will identify early phenotypes of sarcomere mutations and improve understanding of disease mechanisms Mutation carriers without LVH will be targeted for preventive treatment trials
	Accurate identification of disease phenocopies	Genetic testing reveals Fabry disease and the patient is referred for multi-system care and potential enzyme replacement therapy A LAMP2 mutation is identified and evaluation for cardiac transplantation is initiated early, just before precipitous clinical deterioration
	Definition of disease etiology	Reassurance for genotype-negative family members, including older relatives who may have LVH due to HTN	Improve understanding of disease pathogenesis Support development of new treatment strategies based on mechanistic insights
Limitations	Genotype-phenotype correlations are still emerging	Results currently may not change management	More comprehensive and longitudinal studies of mutation carriers will identify more precise phenotypes
	Incomplete knowledge of all genes associated with LVH	Negative genetic testing results are not informative	Next generation sequencing will allow a larger number of genes to be analyzed simultaneously and will detect a greater variety of mutations, including copy number variants
	Pathogenicity of DNA variants can be ambiguous	Genetic test results may currently be difficult to interpret If variant pathogenicity is uncertain, genotype cannot be used for clinical decision-making	Improved assays to determine pathogenicity are in development Increasing numbers of genotyped patients will improve assignment of pathogenicity
	Genetic testing is expensive	Genetic testing may not currently be feasible for all patients	Next generation sequencing will substantially reduce costs