ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.53G>A (p.Arg18Gln) (rs41311087)

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Total submissions: 5
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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 RCV000058779 SCV000090299 not provided Congenital long QT syndrome no assertion provided literature only This variant has been reported as associated with Long QT syndrome in the following publications (PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
GeneDx RCV000766749 SCV000520830 uncertain significance not provided 2017-01-12 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN5A gene. The c.392+6 C>A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The nucleotide, cytosine (C), at this splice sequence position is conserved across species. This variant is predicted to cause abnormal gene splicing and may lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. However, to our knowledge no studies have been performed to determine the functional effect of the c.392+6 C>A variant and the physiological consequence of this variant cannot be precisely determined.
Invitae RCV000802409 SCV000942240 uncertain significance Brugada syndrome 2018-12-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 18 of the SCN5A protein (p.Arg18Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs41311087, ExAC 0.02%). This variant has been observed in individuals affected with sudden unexplained death, suspected or definite Brugada syndrome, or suspected Long QT syndrome (PMID: 26164358, 19716085, 21273195, 20129283). ClinVar contains an entry for this variant (Variation ID: 48306). Experimental studies have shown that this missense change does not affect protein function (PMID: 23805106). 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000041626 SCV000065322 uncertain significance not specified 2018-04-10 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000041626 SCV000748021 uncertain significance not specified 2017-07-03 criteria provided, single submitter clinical testing

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