ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.874G>A (p.Gly292Ser)

gnomAD frequency: 0.00002  dbSNP: rs199473085
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000987234 SCV001136484 uncertain significance Brugada syndrome 1 2019-05-28 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001842416 SCV001354419 uncertain significance Cardiac arrhythmia 2022-12-19 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 292 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 been reported in an individual affected with Brugada syndrome (PMID: 15277732), in an individual affected with long QT syndrome (PMID: 30246897), and in an individual affected with dilated cardiomyopathy (PMID: 31521807). This variant has also been identified in 10/280512 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.
Invitae RCV003656625 SCV001507583 uncertain significance not provided 2023-04-19 criteria provided, single submitter clinical testing 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. Experimental studies have shown that this missense change affects SCN5A function (PMID: 21840964, 25261036). 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. ClinVar contains an entry for this variant (Variation ID: 68053). This missense change has been observed in individual(s) with SCN5A-related conditions (PMID: 15277732, 30246897). This variant is present in population databases (rs199473085, gnomAD 0.04%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 292 of the SCN5A protein (p.Gly292Ser).
Fulgent Genetics, Fulgent Genetics RCV002498348 SCV002799609 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 2022-03-08 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001842416 SCV004815056 uncertain significance Cardiac arrhythmia 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 292 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 been reported in an individual affected with Brugada syndrome (PMID: 15277732), in an individual affected with long QT syndrome (PMID: 30246897), and in an individual affected with dilated cardiomyopathy (PMID: 31521807). This variant has also been identified in 10/280512 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 RCV004019066 SCV004944540 uncertain significance Cardiovascular phenotype 2020-01-30 criteria provided, single submitter clinical testing The c.874G>A (p.G292S) alteration is located in exon 7 (coding exon 6) of the SCN5A gene. This alteration results from a G to A substitution at nucleotide position 874, causing the glycine (G) at amino acid position 292 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust RCV000058856 SCV000090376 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (PMID:15277732). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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