Submissions for variant NM_000335.5(SCN5A):c.688A>G (p.Ile230Val)

dbSNP: rs199473074

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003541031	SCV001380967	uncertain significance	not provided	2019-10-18	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine with valine at codon 230 of the SCN5A protein (p.Ile230Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). This variant has been observed in an individual affected with Brugada syndrome (PMID: 11901046). ClinVar contains an entry for this variant (Variation ID: 68035). This variant is present in population databases (rs199473074, ExAC 0.01%).
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058838	SCV000090358	not provided	Brugada syndrome		no assertion provided	literature only	This variant has been reported as associated with Brugada syndrome in the following publications (PMID:11901046). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.