Interpretation and actionability of genetic variants in cardiomyopathies: a position statement from the European Society of Cardiology Council on cardiovascular genomics
Eloisa Arbustini, Elijah R. Behr, Lucie Carrier, Cornelia M. van Duijn, Paul C. Evans, Valentina Favalli, Pim van der Harst, Kristina H. Haugaa, Guillaume Jondeau, Stefan Kääb, Juan Pablo Kaski, Maryam Kavousi, Bart Loeys, Antonis Pantazis, Yigal M. Pinto, Heribert Schunkert, Alessandro Di Toro, Thomas Thum, Mario Urtis, Johannes Waltenberger, Perry Elliott
Abstract
This document describes the contribution of clinical criteria to the interpretation of genetic variants using heritable Mendelian cardiomyopathies as an example. The aim is to assist cardiologists in defining the clinical contribution to a genetic diagnosis and the interpretation of molecular genetic reports. The identification of a genetic variant of unknown or uncertain significance is a limitation of genetic testing, but current guidelines for the interpretation of genetic variants include essential contributions from clinical family screening that can establish a de novo assignment of the variant or its segregation with the phenotype in the family. A partnership between clinicians and patients helps to solve major uncertainties and provides reliable and clinically actionable information.