ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.5803G>A (p.Gly1935Ser) (rs199473637)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000058807 SCV000812435 uncertain significance Brugada syndrome 2020-03-26 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 1935 of the SCN5A protein (p.Gly1935Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs199473637, ExAC 0.01%). This variant has been reported in individual(s) with long QT syndrome, unexplained sudden death, and suspected or confirmed Brugada syndrome (PMID: 16267250, 27816319, 18508782, 20129283). ClinVar contains an entry for this variant (Variation ID: 68011). Experimental studies have shown that this missense change enhances the SCN5A channel slow inactivation (PMID: 16267250, 17854786). 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 RCV000764500 SCV000895571 uncertain significance Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1, autosomal recessive; Progressive familial heart block, type 1A; Paroxysmal familial ventricular fibrillation 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10 2018-10-31 criteria provided, single submitter clinical testing
Color Health, Inc RCV000777698 SCV000913631 uncertain significance Arrhythmia 2020-12-10 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 1935 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). A functional study has shown that the mutant cardiac sodium channel exhibited enhanced slow inactivation compared with the wild-type channel (PMID: 16267250). This variant has been reported in individuals with and suspected with Brugada syndrome (PMID: 16267250, 20129283), one individual with long QT syndrome (PMID: 27816319), and one individual from a family with a possible sudden arrhythmic death syndrome (SADS) death (PMID: 18508782). This variant has been identified in 7/248912 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.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058807 SCV000090327 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (PMID:16267250;PMID:18508782;PMID:20129283). 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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