Submissions for variant NM_000335.5(SCN5A):c.1569T>A (p.Arg523=)

gnomAD frequency: 0.00351  dbSNP: rs41313693

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000151796	SCV000200257	benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.Arg523Arg in Exon 12 of SCN5A: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence and has been identified in 1.1% (37/3408) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs41313693).
Invitae	RCV000713133	SCV000291779	benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000373129	SCV000444147	uncertain significance	Paroxysmal familial ventricular fibrillation	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000280959	SCV000444148	uncertain significance	Long QT syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000319566	SCV000444149	uncertain significance	Congenital long QT syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000376534	SCV000444150	uncertain significance	Progressive familial heart block	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000227443	SCV000444151	uncertain significance	Brugada syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000341319	SCV000444152	uncertain significance	Sick sinus syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000407616	SCV000444153	uncertain significance	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000619072	SCV000736342	benign	Cardiovascular phenotype	2016-08-22	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Athena Diagnostics	RCV000713133	SCV000843704	benign	not provided	2017-10-26	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001842473	SCV000904517	benign	Cardiac arrhythmia	2018-08-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000713133	SCV001840921	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000713133	SCV002048404	benign	not provided	2020-10-20	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001842473	SCV004815012	benign	Cardiac arrhythmia	2024-02-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000713133	SCV005042335	benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	SCN5A: BP4, BP7, BS1, BS2
Roden Lab, Vanderbilt University Medical Center	RCV004698472	SCV005200406	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, 3-38604033-A-T was evaluated for association with the loss-of-function condition Brugada Syndrome.This Variant had an AF of 0.003206855 in gnomAD v3The in silico predictor SpliceAI scored the variant as 0.0688; 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000713133	SCV001744903	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000151796	SCV001923507	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000151796	SCV001968668	benign	not specified		no assertion criteria provided	clinical testing