Dominant negative effects of SCN5A missense variants.

ABSTRACT:

Purpose

Up to 30% of patients with Brugada syndrome (BrS) carry loss-of-function (LoF) variants in the cardiac sodium channel gene SCN5A encoding for the protein Na_V1.5. Recent studies suggested that Na_V1.5 can dimerize, and some variants exert dominant negative effects. In this study, we sought to explore the generality of missense variant Na_V1.5 dominant negative effects and their clinical severity.

Methods

We identified 35 LoF variants (<10% of wild type [WT] peak current) and 15 partial LoF variants (10%-50% of WT peak current) that we assessed for dominant negative effects. SCN5A variants were studied in HEK293T cells, alone or in heterozygous coexpression with WT SCN5A using automated patch clamp. To assess the clinical risk, we compare

SUBMITTER: O'Neill MJ 

PROVIDER: S-EPMC9262418 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature