ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.3663+10T>C (rs200656652)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000151782 SCV000200233 likely benign not specified 2013-07-18 criteria provided, single submitter clinical testing 3666+10T>C in intron 20 of SCN5A: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 1/110 Puerto Rican chromosomes by the 1000 Geno mes Project (dbSNP rs200656652). 3666+10T>C in intron 20 of SCN5A (rs200656652; allele frequency = 1/110)
GeneDx RCV000151782 SCV000514548 benign not specified 2015-03-11 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.
Invitae RCV000465098 SCV000557127 likely benign Brugada syndrome 2020-11-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000151782 SCV001363351 likely benign not specified 2019-10-29 criteria provided, single submitter clinical testing Variant summary: SCN5A c.3666+10T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.8e-05 in 247860 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in SCN5A causing Arrhythmia (4.8e-05 vs 0.0001), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.3666+10T>C in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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