Submissions for variant NM_000335.5(SCN5A):c.3664-7T>A

gnomAD frequency: 0.00005  dbSNP: rs373156650

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000127980	SCV000171570	benign	not specified	2014-05-16	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	RCV003326355	SCV000760246	likely benign	not provided	2023-12-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003326355	SCV001248650	likely benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	SCN5A: BP4, BS2
Color Diagnostics, LLC DBA Color Health	RCV001842452	SCV001341854	likely benign	Cardiac arrhythmia	2018-12-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000127980	SCV002074195	uncertain significance	not specified	2022-01-10	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001842452	SCV004821518	likely benign	Cardiac arrhythmia	2023-12-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004017415	SCV004849277	uncertain significance	Cardiovascular phenotype	2016-11-12	criteria provided, single submitter	clinical testing	The c.3667-7T>A intronic alteration consists of a T to A substitution 7 nucleotides before coding exon 20 in the SCN5A gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Roden Lab, Vanderbilt University Medical Center	RCV004698470	SCV005200467	likely benign	Brugada syndrome 1		criteria provided, single submitter	research	We classified this variant using data from the calibrated functional assay 'ParSE-seq' (PMID: 37732247), population data, and in silico data within the ACMG v3 framework (PMID: 25741868)The SCN5A variant, 3-38566589-A-T was evaluated for association with the loss-of-function condition Brugada Syndrome.This Variant had an AF of 0.000046 in gnomAD v3The in silico predictor SpliceAI scored the variant as 0.01; normal <0.2, likely damaging >0.5.Using the functional RNA-splicing assay, ParSE-seq, the variant was evaluated to have no impact on splicing (BS3_strong) following the Brnich et al. calibration framework (PMID: 31892348). We do not apply benign splicing functional data to missense variants. In aggregate, we therefore classify this variant as LB using these collective data.