ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.362G>A (p.Arg121Gln) (rs199473058)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000058583 SCV000545081 pathogenic Brugada syndrome 2017-10-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 121 of the SCN5A protein (p.Arg121Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in individuals affected with Brugada syndrome (PMID: 20129283) and sudden unexplained nocturnal death syndrome (PMID: 24529773). ClinVar contains an entry for this variant (Variation ID: 67808). A different missense substitution at this codon (p.Arg121Trp) has been determined to be pathogenic (PMID: 22739120). This suggests that the arginine residue is critical for SCN5A protein function and that other missense substitutions at this position may also be pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058583 SCV000090103 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (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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