Submissions for variant NM_000335.5(SCN5A):c.1673A>G (p.His558Arg)

gnomAD frequency: 0.24768  dbSNP: rs1805124

Total submissions: 29

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000041604	SCV000050841	benign	not specified	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041604	SCV000065300	benign	not specified	2012-08-09	criteria provided, single submitter	clinical testing	27% (1151/5339) of Afr Amer chrom in ESP
Eurofins Ntd Llc (ga)	RCV000041604	SCV000225722	benign	not specified	2014-11-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000041604	SCV000306537	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000251327	SCV000317411	benign	Cardiovascular phenotype	2015-03-16	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	RCV000987225	SCV000444132	likely benign	Brugada syndrome 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000406777	SCV000444133	likely benign	Progressive familial heart block, type 1A	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000300603	SCV000444134	likely benign	Long QT syndrome 3	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000339196	SCV000444135	likely benign	Congenital long QT syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000405409	SCV000444136	likely benign	Ventricular fibrillation, paroxysmal familial, type 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000304709	SCV000444137	likely benign	Sick sinus syndrome 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000361696	SCV000444138	likely benign	Dilated cardiomyopathy 1E	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Athena Diagnostics	RCV000058440	SCV000843708	benign	not provided	2017-04-20	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001841593	SCV000910524	benign	Cardiac arrhythmia	2018-03-15	criteria provided, single submitter	clinical testing
Invitae	RCV000058440	SCV001000234	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000987225	SCV001136474	benign	Brugada syndrome 1	2019-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000058440	SCV001158905	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000041604	SCV001433065	benign	not specified	2020-03-05	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000987225	SCV001440390	benign	Brugada syndrome 1	2019-01-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000058440	SCV001840837	benign	not provided	2020-04-22	criteria provided, single submitter	clinical testing	Observed in 62556/280350 alleles (22.31%), including 7355 homozygous individuals, in large population cohorts, suggesting the variant is benign (Lek et al., 2016); Reported in ClinVar as likely benign or benign (ClinVar Variant ID# 48289; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 16864729, 26606670, 24332189, 30968627, 26084969, 27554632, 29202755, 27381756, 18368697, 26846766, 27153395, 12569159, 21216356, 21076409, 18803136, 19549036, 20384651, 24388587, 15599693, 22370996, 22064211, 15992732, 21109022, 15851227, 20129283, 25177937, 17185997, 24762593, 14500339, 21840964, 24951663, 21705349, 31043699)
Fulgent Genetics, Fulgent Genetics	RCV002496658	SCV002805784	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	2022-04-28	criteria provided, single submitter	clinical testing
Cohesion Phenomics	RCV003125879	SCV003803686	benign	Primary dilated cardiomyopathy	2022-09-27	criteria provided, single submitter	clinical testing
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058440	SCV000089960	not provided	not provided		no assertion provided	literature only	This variant has been reported in the following publications (PMID:10807545;PMID:11463728;PMID:11997281;PMID:12569159;PMID:12639704;PMID:14760488;PMID:14985827;PMID:15161528;PMID:15599693;PMID:15689442;PMID:16132053;PMID:16155735;PMID:16239976;PMID:16712702;PMID:17161064;PMID:17210839;PMID:17675083;PMID:17993325;PMID:18093912;PMID:18156160;PMID:18362431;PMID:18426444;PMID:19083750;PMID:19841300;PMID:20129283).
Stanford Center for Inherited Cardiovascular Disease, Stanford University	RCV000058440	SCV000924939	benign	not provided	2011-07-18	no assertion criteria provided	provider interpretation
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000041604	SCV001741215	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000041604	SCV001918416	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000041604	SCV001930899	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000041604	SCV001959661	benign	not specified		no assertion criteria provided	clinical testing
Biology Molecular and Stem Cell Facilities Laboratory, National Cardiovascular Center, Harapan Kita Hospital	RCV000058440	SCV003802758	pathogenic	not provided		no assertion criteria provided	research	Allele Freq Eas (0.1012); Sift: tolerated (1); PolyPhen: benign (0)