Automated patch clamp data improve variant classification and penetrance stratification for SCN5A-Brugada syndrome.

ABSTRACT:

Background and aims

Brugada Syndrome (BrS) is an inherited arrhythmia disorder that causes an elevated risk of sudden cardiac death. Approximately 20% of patients with BrS have rare variants in SCN5A, which encodes the cardiac sodium channel NaV1.5. Genetic workup of BrS is often complicated by SCN5A variants of uncertain significance (VUS) and/or incomplete penetrance. This study deployed an SCN5A-BrS functional assay at cohort scale to facilitate the implementation of genetic and precision medicine.

Methods

All 252 missense and in-frame insertion/deletion SCN5A variants from a previously published large cohort of BrS cases (n = 3335 patients) were analysed using a calibrated high-throughput automated patch-clamp (APC) assay. Variant functional Z-scores were assigned eviden

SUBMITTER: O'Neill MJ 

PROVIDER: S-EPMC12678899 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature