ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.1595T>G (p.Phe532Cys) (rs199473573)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182979 SCV000235378 likely pathogenic not provided 2012-12-06 criteria provided, single submitter clinical testing p.Phe532Cys (TTT>TGT):c.1595 T>G in exon 12 of the SCN5A gene (NM_198056.2) The Phe532Cys variant in the SCN5A gene has been reported previously in one Japanese individual with paryoxysmal atrial fibrillation and atrial tachycardia, and was absent from 232 Japanese control samples in this study (Maekawa K et al., 2005). Phe532Ser was also reported in one individual from a Japanese cohort of sudden infant death syndrome (SIDS) cases and was absent from 150 Japanese control samples in this study (Otagiri T et al., 2008). However, expression studies showed that Phe532Cys did not have a functional effect on the sodium channel (Otagiri T et al., 2008). Nevertheless, mutations in nearby residues (Ser524Tyr, Arg526His, Phe530Val, Arg535Gln) have been reported in association with arrhythmia, further supporting the functional importance of this region of the protein. The Phe532Cys variant was absent from the 1000 Genomes database (Kersey P et al., 2010), and the NHLBI ESP Exome Variant Server reports Phe532Cys was not observed in approximately 6000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. In summary, Phe532Cys in the SCN5A gene is a good candidate for a disease-causing mutation. The variant is found in BRUGADA panel(s).
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000490338 SCV000267490 uncertain significance SUDDEN INFANT DEATH SYNDROME 2016-03-18 criteria provided, single submitter reference population
Color RCV001178346 SCV001342757 uncertain significance Arrhythmia 2020-01-24 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058434 SCV000089954 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (PMID:15996170;PMID:18596570;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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