Submissions for variant NM_000335.5(SCN5A):c.5782C>T (p.Arg1928Cys)

gnomAD frequency: 0.00003  dbSNP: rs267599786

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003539789	SCV000825947	uncertain significance	not provided	2024-10-16	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1929 of the SCN5A protein (p.Arg1929Cys). This variant is present in population databases (rs267599786, gnomAD 0.003%). This missense change has been observed in individual(s) with Brugada syndrome (PMID: 30193851). ClinVar contains an entry for this variant (Variation ID: 75052). 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 disruptive. 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.
Color Diagnostics, LLC DBA Color Health	RCV001842422	SCV001734093	uncertain significance	Cardiac arrhythmia	2023-10-17	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with cysteine at codon 1929 of the SCN5A protein. This variant is found within the highly conserved C-terminal region (a.a. 1773-2016). 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). 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 individual(s) affected with Brugada syndrome (PMID: 16643399, 30193851, 32893267). This variant has been identified in 5/280546 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.
All of Us Research Program, National Institutes of Health	RCV001842422	SCV004833803	uncertain significance	Cardiac arrhythmia	2024-07-29	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with cysteine at codon 1929 of the SCN5A protein. This variant is found within the highly conserved C-terminal region (a.a. 1773-2016). 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). 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 individual(s) affected with Brugada syndrome (PMID: 16643399, 30193851, 32893267). This variant has been identified in 5/280546 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	RCV003539789	SCV005198156	uncertain significance	not provided	2023-11-01	criteria provided, single submitter	clinical testing