Multi-site validation of a functional assay to adjudicate SCN5A Brugada Syndrome-associated variants.

ABSTRACT: Brugada Syndrome (BrS) is an inheritable arrhythmia condition that is associated with rare, loss-of-function variants in the cardiac sodium channel gene, SCN5A. Interpreting the pathogenicity of SCN5A missense variants is challenging and ~79% of SCN5A missense variants in ClinVar are currently classified as Variants of Uncertain Significance (VUS). An in vitro SCN5A-BrS automated patch clamp assay was generated for high-throughput functional studies of Na_V1.5. The assay was independently studied at two separate research sites - Vanderbilt University Medical Center and Victor Chang Cardiac Research Institute - revealing strong correlations, including peak I_Na density (R²=0.86). The assay was calibrated according to C

SUBMITTER: Ma JG 

PROVIDER: S-EPMC10775332 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature