Functionally validated SCN5A variants allow interpretation of pathogenicity and prediction of lethal events in Brugada syndrome.

In vitro functional validation is key to classifying the pathogenicity of SCN5A VUSs and for risk stratification of genetic predictors of LAEs. Functionally proven LOF-SCN5A mutations are genetic burdens of sudden death in BrS, but evidence for other BrS-associated genes is elusive.