ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.100_101CG[1] (p.Gly35fs) (rs1131691708)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493678 SCV000582682 pathogenic not provided 2017-05-02 criteria provided, single submitter clinical testing Although the c.102_103delCG pathogenic variant in the SCN5A gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon glycine 35, changing it to a leucine, and creating a premature stop codon at position 53 of the new reading frame, denoted p.G35LfsX53. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Many other frameshift variants in the SCN5A gene have been reported in Human Gene Mutation Database in association with Brugada syndrome (Stenson et al., 2014). Furthermore, c.102_103delCG has not been observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In summary, c.102_103delCG is interpreted as a pathogenic variant
Invitae RCV000560463 SCV000637068 pathogenic Brugada syndrome 2017-03-23 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides from exon 2 of the SCN5A mRNA (c.102_103delCG), causing a frameshift at codon 35. This creates a premature translational stop signal (p.Gly35Leufs*53) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in SCN5A are known to be pathogenic (PMID: 20129283, 22789973). For these reasons, this variant has been classified as Pathogenic.

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