ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.3804+1G>A

gnomAD frequency: 0.00001  dbSNP: rs1363445455
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001961835 SCV002135951 uncertain significance Brugada syndrome 2022-02-03 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 21 of the SCN10A 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), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SCN10A cause disease.
Ambry Genetics RCV002361126 SCV002625441 uncertain significance Cardiovascular phenotype 2022-10-24 criteria provided, single submitter clinical testing The c.3804+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 21 of the SCN10A gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. 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; however, loss of function of SCN10A has not been established as a mechanism of disease. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.

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