ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.5800G>A (p.Gly1934Ser) (rs199473637)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
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.
Color RCV000777698 SCV000913631 uncertain significance Arrhythmia 2018-10-05 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the C-terminal region of the SCN5A protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 7/245988 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
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
Invitae RCV000058807 SCV000812435 uncertain significance Brugada syndrome 2018-06-08 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 an individuals affected with Brugada syndrome, long QT syndrome and unexplained sudden death and in an individual referred for genetic testing for 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.

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