ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.4343T>C (p.Ile1448Thr) (rs199473251)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV001192712 SCV001361004 uncertain significance not specified 2019-11-04 criteria provided, single submitter clinical testing Variant summary: SCN5A c.4343T>C (p.Ile1448Thr) results in a non-conservative amino acid change located in the Ion transport domain (IPR005821) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 248530 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4343T>C has been reported in the literature in individuals affected with Brugada Syndrome (Kapplinger_2016, Walsh_2014). These reports however, do not provide unequivocal conclusions about association of the variant with Brugada Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Different variants affecting the same codon (p.I1448L and p.I1448N) have been reported in patients in HGMD database. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058663 SCV000090183 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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