ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.703+6A>G

dbSNP: rs781104838
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000827549 SCV000291833 uncertain significance not provided 2023-08-22 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 242207). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change falls in intron 6 of the SCN5A gene. It does not directly change the encoded amino acid sequence of the SCN5A protein. It affects a nucleotide within the consensus splice site.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000602219 SCV000712013 uncertain significance not specified 2016-04-15 criteria provided, single submitter clinical testing The c.703+6A>G variant in SCN5A has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/20178 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 781104838). This variant is located in the 5' splice region. Computational tools do not suggest an impact to splicing. However, this information is not predicti ve enough to rule out pathogenicity. In summary, the clinical significance of th e c.703+6A>G variant is uncertain.
GeneDx RCV000827549 SCV000969202 likely benign not provided 2018-05-21 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Diagnostics, LLC DBA Color Health RCV001843008 SCV001733888 uncertain significance Cardiac arrhythmia 2021-08-26 criteria provided, single submitter clinical testing This variant causes an A to G nucleotide substitution at the +6 position of intron 6 of the SCN5A gene. Splice prediction tools and conservation analysis are inconclusive regarding the impact of this variant on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/216992 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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