ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.934+4C>T (rs182050752)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000620739 SCV000737385 uncertain significance Cardiovascular phenotype 2015-10-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000544310 SCV000637210 uncertain significance Brugada syndrome 2018-11-30 criteria provided, single submitter clinical testing This sequence change falls in intron 7 of the SCN5A gene. It does not directly change the encoded amino acid sequence of the SCN5A protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs182050752, ExAC 0.05%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with Brugada syndrome (PMID: 20129283). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant has uncertain impact on SCN5A function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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