Submissions for variant NM_000335.5(SCN5A):c.1381T>G (p.Leu461Val)

gnomAD frequency: 0.00352  dbSNP: rs41313697

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171822	SCV000055223	benign	Sudden cardiac death	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000222830	SCV000269796	benign	not specified	2015-05-20	criteria provided, single submitter	clinical testing	p.Leu461Val in exon 11 of SCN5A: This variant is not expected to have clinical s ignificance because it has been identified in 1.2% (104/8926) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs41313697).
Ambry Genetics	RCV000253238	SCV000319103	benign	Cardiovascular phenotype	2015-09-28	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
Eurofins Ntd Llc (ga)	RCV000222830	SCV000335142	benign	not specified	2015-09-28	criteria provided, single submitter	clinical testing
Invitae	RCV000058418	SCV000557124	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001842278	SCV000904501	benign	Cardiac arrhythmia	2018-04-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001148789	SCV001309700	benign	Dilated cardiomyopathy 1E	2018-12-19	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001253991	SCV001429882	likely benign	Brugada syndrome 1	2018-12-19	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001253992	SCV001429883	benign	Sick sinus syndrome 1	2018-12-19	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001253993	SCV001429884	benign	Ventricular fibrillation, paroxysmal familial, type 1	2018-12-19	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001253994	SCV001429885	benign	Long QT syndrome 3	2018-12-19	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001253995	SCV001429886	benign	Progressive familial heart block, type 1A	2018-12-19	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
GeneDx	RCV000058418	SCV001836573	benign	not provided	2020-04-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32880476, 28412158, 16712702, 15851227, 20129283)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000058418	SCV002050272	benign	not provided	2023-03-28	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002490651	SCV002803157	likely 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	2021-08-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000058418	SCV004698327	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	SCN5A: BS1, BS2
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058418	SCV000089938	not provided	not provided		no assertion provided	literature only	This variant has been reported in the following publications (PMID:15851227;PMID:16712702;PMID:18508782;PMID:19841300;PMID:20129283).
Clinical Genetics, Academic Medical Center	RCV000222830	SCV002034602	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000222830	SCV002036441	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000058418	SCV002037236	likely benign	not provided		no assertion criteria provided	clinical testing