Submissions for variant NM_000335.5(SCN5A):c.1058C>T (p.Thr353Ile)

dbSNP: rs199473096

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003480052	SCV001574355	pathogenic	not provided	2024-03-11	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 353 of the SCN5A protein (p.Thr353Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Brugada syndrome (PMID: 17198989). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 67631). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 32533946) indicates that this missense variant is expected to disrupt SCN5A function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SCN5A function (PMID: 17198989, 25261036). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic	RCV003480052	SCV004226750	likely pathogenic	not provided	2023-03-29	criteria provided, single submitter	clinical testing	PP1_moderate, PP3, PM1, PM2_supporting, PS3_moderate, PS4_moderate
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058387	SCV000089907	not provided	Brugada syndrome		no assertion provided	literature only	This variant has been reported as associated with Brugada syndrome in the following publications (PMID:17198989). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.