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

gnomAD frequency: 0.00041  dbSNP: rs200656652

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003764925	SCV000557127	likely benign	not provided	2025-01-20	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000151782	SCV001363351	likely benign	not specified	2025-02-03	criteria provided, single submitter	clinical testing	Variant summary: SCN5A c.3666+10T>C alters a conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation 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 estimated 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. ClinVar contains an entry for this variant (Variation ID: 165140). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV004544363	SCV004773840	likely benign	SCN5A-related disorder	2020-02-17	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).