Abstract
Hypertrophic cardiomyopathy (HCM) is a frequent inherited heart disease with an estimated prevalence of up to 1 in 200 individuals. In the majority of cases, HCM is inherited as an autosomal dominant genetic trait with pathogenic variants detected in sarcomeric proteins.
Nevertheless, the genetic basis of HCM is more complex. More than 2 000 mutations in 27 genes have been described in association with HCM.
The genetic and allelic heterogeneity makes molecular analysis by conventional methods time-consuming and expensive. Next Generation Sequencing (NGS) based genomic testing allows rapid analysis of a large number of genes or even a whole genome at similar cost and accuracy to conventional sequencing methods.
Screening large numbers of genes results in the identification of many genetic variants of uncertain significance and makes the results interpretation difficult. The process of classification the genetic variants is very complex.
Genetic screening is an important tool for clinical management of HCM patients and enables mutation-specific confirmatory testing of the appropriate family members. The yield of genetic testing is variable, about 20-40 %.
For predicting the diagnostic yield of genetic testing, clinical scoring systems have been developed. Identifying the genetic basis of HCM creates remarkable opportunities to understand how disease develops, and by extension, how to disrupt the disease progression in the future.