ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.3995_3999del (p.Pro1332fs) (rs1553695398)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498436 SCV000590489 likely pathogenic not provided 2017-06-13 criteria provided, single submitter clinical testing Although the c.3995_3999delCGTCC likely pathogenic variant in the SCN5A gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon proline 1332, changing it to a histidine, and creating a premature stop codon at position 52 of the new reading frame, denoted p.Pro1332HisfsX52. This likely 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. Other frameshift variants in the SCN5A gene have been reported in Human Gene Mutation Database in association with SCN5A-related disorders (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.3995_3999delCGTCC variant has not been observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Invitae RCV001042061 SCV001205722 pathogenic Brugada syndrome 2020-01-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro1332Hisfs*52) in the SCN5A gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 432733). 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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