ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.2103del (p.Leu702fs) (rs794728911)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183152 SCV000235568 likely pathogenic not provided 2015-12-10 criteria provided, single submitter clinical testing Although the c.2103delG 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 Leucine 207, changing it to a Cysteine, and creating a premature stop codon at position 9 of the new reading frame, denoted p.Leu702CysfsX9. This 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 HGMD in association with SCN5A-related disorders (Stenson et al., 2014). Furthermore, the c.2103delG variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.
Invitae RCV000638679 SCV000760218 pathogenic Brugada syndrome 2018-05-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu702Cysfs*9) 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 disease. ClinVar contains an entry for this variant (Variation ID: 201558). 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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