ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.3509-1G>C

dbSNP: rs1553698563
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586276 SCV000700034 likely pathogenic Long QT syndrome 1 2016-01-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV002456294 SCV002616370 likely pathogenic Cardiovascular phenotype 2018-05-21 criteria provided, single submitter clinical testing The c.3512-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 19 of the SCN5A gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003767344 SCV003028545 likely pathogenic not provided 2023-08-11 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 19 of the SCN5A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SCN5A are known to be pathogenic (PMID: 20129283, 22789973). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 496573). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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