Clinical predictors of informative genetic testing in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is characterised by unexplained left ventricular hypertrophy in the absence of increased afterload. It is often a result of variants in sarcomeric genes including those that code for the actin and myosin filaments, the z discs and some calcium handling proteins. Mutations in MYBPC3 (affecting the myosin binding protein), MYH7 (affecting the myosin filament), TNNT2 and TNNI3 (affecting the actin filament) have been reported as the most frequent. Non-sarcomeric mutations are less common. Patients suspected of having HCM can undergo genetic testing. The benefits of genetic testing lie predominantly in using details of a pathogenic mutation to assess risk in other family members, but some mutations can give useful prognostic information. The study aimed to identify clinical parameters that can predict an informative result in patients suspected of having HCM. A retrospective analysis of 126 consecutive unrelated patients undergoing genetic testing with a confirmed diagnosis of HCM was conducted in a tertiary cardiomyopathy service between January 2014–June 2016. A standard 19-gene panel using next generation sequencing (Oxford Molecular Genetics Laboratory, UK) was used. Informative results included class 4 or 5 variants deemed ‘pathogenic’ or ‘likely pathogenic’.