Submissions for variant NM_000335.5(SCN5A):c.5795G>C (p.Gly1932Ala)

dbSNP: rs758704113

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003434363	SCV002209776	uncertain significance	not provided	2023-09-26	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1933 of the SCN5A protein (p.Gly1933Ala). This variant is present in population databases (rs758704113, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1432998). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
CeGaT Center for Human Genetics Tuebingen	RCV003434363	SCV004149389	uncertain significance	not provided	2023-07-01	criteria provided, single submitter	clinical testing	SCN5A: PM2:Supporting
Color Diagnostics, LLC DBA Color Health	RCV003591904	SCV004361595	uncertain significance	Cardiac arrhythmia	2023-11-14	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with alanine at codon 1933 of the SCN5A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). This variant is found within a highly conserved C-terminus region (a.a. 1772-2016). Rare non-truncating variants in this region have been shown to be significantly overrepresented in individuals with Brugada syndrome and long QT syndrome (PMID: 32893267). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 6/280410 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.
GeneDx	RCV003434363	SCV005201201	uncertain significance	not provided	2023-12-12	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.