ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.4217G>A (p.Gly1406Glu) (rs199473609)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183063 SCV000235472 pathogenic not provided 2014-05-11 criteria provided, single submitter clinical testing The G1406E mutation in the SCN5A gene has been reported previously in two unrelated patients with Brugada syndrome and the mutation was absent from at least 2,600 control alleles (Kapplinger J et al., 2010). Additionally, the G1406E mutation 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. Furthermore, the G1406E mutation is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this mutation is probably damaging to the protein structure/function. A missense mutation in the same residue (G1406R) and in nearby residues (V1405L, V1405M, G1408R, Y1409C) have been reported in association with Brugada syndrome, supporting the functional importance of this residue and region of the protein. In summary, G1406E in the SCN5A gene is interpreted as a disease-causing mutation. The variant is found in BRUGADA panel(s).
Color RCV001178348 SCV001342759 uncertain significance Arrhythmia 2020-02-10 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058648 SCV000090168 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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