ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.2621G>A (p.Gly874Asp)

gnomAD frequency: 0.00001  dbSNP: rs765698507
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003541119 SCV001214763 uncertain significance not provided 2019-12-04 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 874 of the SCN5A protein (p.Gly874Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs765698507, ExAC 0.009%). This variant has not been reported in the literature in individuals with SCN5A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Fulgent Genetics, Fulgent Genetics RCV002489615 SCV002778355 uncertain significance Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1; Progressive familial heart block, type 1A; Ventricular fibrillation, paroxysmal familial, type 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10 2021-08-10 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV003591833 SCV004361683 uncertain significance Cardiac arrhythmia 2022-11-06 criteria provided, single submitter clinical testing This missense variant replaces glycine with aspartic acid at codon 874 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SCN5A-related disorders in the literature. This variant has been identified in 2/251116 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 RCV003591833 SCV004837533 uncertain significance Cardiac arrhythmia 2024-05-30 criteria provided, single submitter clinical testing This missense variant replaces glycine with aspartic acid at codon 874 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SCN5A-related disorders in the literature. This variant has been identified in 2/251116 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.
Ambry Genetics RCV004986768 SCV005500154 uncertain significance Cardiovascular phenotype 2024-06-25 criteria provided, single submitter clinical testing The p.G874D variant (also known as c.2621G>A), located in coding exon 15 of the SCN5A gene, results from a G to A substitution at nucleotide position 2621. The glycine at codon 874 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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