Submissions for variant NM_000335.5(SCN5A):c.3575G>A (p.Arg1192Gln)

gnomAD frequency: 0.00222  dbSNP: rs41261344

Total submissions: 24

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171819	SCV000050843	benign	Brugada syndrome	2013-06-24	criteria provided, single submitter	research
GeneDx	RCV000058578	SCV000171568	benign	not provided	2020-04-29	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23465283, 22378279, 22995991, 24784157, 20129283, 15851227, 15992732, 18976777, 23853484, 15121794, 15689442, 22682427, 25051102, 20981092, 22519808, 17605181, 11823453, 26131924, 26159999, 27153395, 15851440, 16568155, 28472724, 28493952, 29672598, 29997009, 28498465, 30419068, 30079003, 31019283, 30677491, 31043699, 31539150, 31751991, 31918855, 28878402, 18245395, 33131149)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154828	SCV000204510	benign	not specified	2013-10-18	criteria provided, single submitter	clinical testing	Arg1193Gln in exon 20 of SCN5A: This variant is not expected to have clinical si gnificance because it has been identified in 5.1% (20/394) Chinese chromosomes b y the 1000 Genomes Project (dbSNP rs41261344).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000058578	SCV000262483	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000154828	SCV000306543	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000252422	SCV000318184	benign	Cardiovascular phenotype	2016-02-01	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.
Illumina Laboratory Services, Illumina	RCV000009990	SCV000443977	benign	Brugada syndrome 1	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000154828	SCV000748020	likely benign	not specified	2016-12-28	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000755697	SCV000883129	benign	Long QT syndrome 3	2018-11-21	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001841238	SCV000910629	benign	Cardiac arrhythmia	2018-03-15	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000058578	SCV001145504	likely benign	not provided	2018-12-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000755697	SCV001308460	benign	Long QT syndrome 3	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV001147624	SCV001308461	likely benign	Progressive familial heart block, type 1A	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001147625	SCV001308462	benign	Sick sinus syndrome 1	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV001147626	SCV001308463	benign	Ventricular fibrillation, paroxysmal familial, type 1	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV001147627	SCV001308464	likely benign	Dilated cardiomyopathy 1E	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000058578	SCV001472663	benign	not provided	2022-03-30	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002476954	SCV002797841	benign	Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1; Progressive familial heart block, type 1A; Ventricular fibrillation, paroxysmal familial, type 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10	2021-10-21	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149566	SCV003838880	benign	Cardiomyopathy	2021-09-15	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000058578	SCV005258477	likely benign	not provided		criteria provided, single submitter	not provided
OMIM	RCV000009990	SCV000030211	pathogenic	Brugada syndrome 1	2006-10-01	no assertion criteria provided	literature only
OMIM	RCV000009991	SCV000030212	risk factor	Long QT syndrome 3, acquired, susceptibility to	2006-10-01	no assertion criteria provided	literature only
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058578	SCV000090098	not provided	not provided		no assertion provided	literature only	This variant has been reported in the following publications (PMID:11823453;PMID:12639704;PMID:15121794;PMID:15689442;PMID:15851227;PMID:16155735;PMID:16707561;PMID:17210839;PMID:17905336;PMID:18245395;PMID:18976777;PMID:19841300;PMID:17605181;PMID:20981092;PMID:20129283).
Blueprint Genetics	RCV000157488	SCV000207233	uncertain significance	Primary familial hypertrophic cardiomyopathy	2014-04-17	no assertion criteria provided	clinical testing