ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.316A>G (p.Ser106Gly)

gnomAD frequency: 0.00001  dbSNP: rs1331765859
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001054084 SCV001218379 uncertain significance Brugada syndrome 2022-03-18 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 106 of the SCN5A protein (p.Ser106Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SCN5A-related conditions (PMID: 29016939, 33213388). ClinVar contains an entry for this variant (Variation ID: 850004). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). Experimental studies have shown that this missense change affects SCN5A function (PMID: 33213388). 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 RCV001842601 SCV001342394 uncertain significance Cardiac arrhythmia 2023-03-24 criteria provided, single submitter clinical testing This missense variant replaces serine with glycine at codon 106 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A functional study has shown that this variant causes an increase in sodium channel current density and affects voltage-dependent activation and inactivation in transfected HEK293 cells (PMID: 33213388). This variant has been reported in two individuals affected with sudden unexplained death or survived cardiac arrest, who showed no ECG abnormalities (PMID: 29016939, 33213388). This variant has not been identified 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.
Fulgent Genetics, Fulgent Genetics RCV002481984 SCV002784162 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 2021-08-26 criteria provided, single submitter clinical testing

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