ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.704-2A>G

dbSNP: rs1553705586
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000609448 SCV000713268 likely pathogenic Brugada syndrome 2017-07-27 criteria provided, single submitter clinical testing The c.704-2A>G variant in SCN5A has not been previously reported in individuals with arrhythmias or in large population studies. This variant occurs in the inva riant region (+/- 1,2) of the splice consensus sequence and is predicted to caus e altered splicing leading to an abnormal or absent protein. Loss of function v ariants in SCN5A are most commonly associated with Brugada syndrome although ove rlap presentations including other SCN5A-related phenotypes (Long QT syndrome) h ave been described (Remme 2013). In summary, although additional studies are req uired to fully establish its clinical significance, the c.704-2A>G variant is li kely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003541554 SCV002248211 likely pathogenic not provided 2024-07-23 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 6 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). Disruption of this splice site has been observed in individual(s) with dilated cardiomyopathy (PMID: 25163546, 33019804). ClinVar contains an entry for this variant (Variation ID: 505834). 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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