High-Throughput Reclassification of SCN5A Variants

Partial or complete loss-of-function variants in SCN5A are the most common genetic cause of the arrhythmia disorder Brugada syndrome (BrS1). However, the pathogenicity of SCN5A variants is often unknown or disputed; 80% of the 1,390 SCN5A missense variants observed in at least one individual to date are variants of uncertain significance (VUSs). The designation of VUS is a barrier to the use of sequence data in clinical care. We selected 83 variants: 10 previously studied control variants, 10 suspected benign variants, and 63 suspected Brugada syndrome-associated variants, selected on the basis of their frequency in the general population and in individuals with Brugada syndrome.

Source: The American Journal of Human Genetics - June 11, 2020 Category: Genetics & Stem Cells Authors: Andrew M. Glazer, Yuko Wada, Bian Li, Ayesha Muhammad, Olivia R. Kalash, Matthew J. O ’Neill, Tiffany Shields, Lynn Hall, Laura Short, Marcia A. Blair, Brett M. Kroncke, John A. Capra, Dan M. Roden Tags: Article Source Type: research