ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.1019G>A (p.Arg340Gln) (rs191009474)

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Total submissions: 2
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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 RCV000058382 SCV000089902 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:15176425;PMID:19862833;PMID:22685113). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Invitae RCV000536656 SCV000637069 uncertain significance Brugada syndrome 2017-07-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 340 of the SCN5A protein (p.Arg340Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs191009474, ExAC 0.04%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in individuals affected with long-QT syndrome (PMID: 15176425) or lone atrial fibrillation (PMID: 21306642, 24144883). ClinVar contains an entry for this variant (Variation ID: 67626). This variant identified in the SCN5A gene is located in the transmembrane spanning DI-S5/S6 region of the resulting protein (PMID: 25348405), but it is unclear how this variant impacts the function of this protein. Experimental studies have shown that this missense change alters the peak current density of the channel and its steady-state inactivation potential (PMID: 22685113). The clinical significance of these findings is unknown. 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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