ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.128G>A (p.Arg43Gln) (rs199473047)

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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 RCV000058412 SCV000089932 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:18848812;PMID:18984535;PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Invitae RCV000537069 SCV000637075 uncertain significance Brugada syndrome 2017-03-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 43 of the SCN5A protein (p.Arg43Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs199473047, ExAC 0.02%). This variant has been reported in the literature in a family affected with atrioventricular block and ventricular tachycardia who also carried a variant in the KCNH2 gene (PMID: 18848812), as well as in one individual referred for longQT genetic testing (PMID: 19716085). ClinVar contains an entry for this variant (Variation ID: 67654). This variant identified in the SCN5A gene is located in the cytoplasmic N-terminal region of the resulting protein (PMID: 25348405). For more information about the location of this variant, please visit www.invitae.com/SCN5A-topology. One experimental study has shown that this missense change disrupts protein function when treated with lidocaine in vitro (PMID: 18848812), however, the clinical significance of this finding is unknown. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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