Submissions for variant NM_000335.5(SCN5A):c.3704A>G (p.Lys1235Arg)

dbSNP: rs199473209

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001842344	SCV001736301	uncertain significance	Cardiac arrhythmia	2020-09-28	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with arginine at codon 1236 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a study population with families affected with Brugada syndrome (PMID: 21126620). This variant has been identified in 1/250732 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV004696677	SCV005198164	uncertain significance	not provided	2022-05-27	criteria provided, single submitter	clinical testing
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058590	SCV000090110	not provided	Brugada syndrome		no assertion provided	literature only	This variant has been reported as associated with Brugada syndrome in the following publications (PMID:21126620). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.