Submissions for variant NM_000335.5(SCN5A):c.1336G>A (p.Glu446Lys)

gnomAD frequency: 0.00007  dbSNP: rs199473339

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000148863	SCV000050614	uncertain significance	Primary dilated cardiomyopathy	2018-04-05	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154845	SCV000204527	likely benign	not specified	2018-04-09	criteria provided, single submitter	clinical testing	proposed classification - variant undergoing re-assessment, contact laboratory
Ambry Genetics	RCV000617704	SCV000735952	benign	Cardiovascular phenotype	2022-05-09	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.
Invitae	RCV003539777	SCV000760307	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001842275	SCV000904470	likely benign	Cardiac arrhythmia	2018-10-20	criteria provided, single submitter	clinical testing
Mendelics	RCV000987232	SCV001136481	uncertain significance	Brugada syndrome 1	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001144225	SCV001304812	likely benign	Progressive familial heart block, type 1A	2019-01-31	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	RCV001144226	SCV001304813	likely benign	Dilated cardiomyopathy 1E	2019-01-31	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	RCV000987232	SCV001304814	likely benign	Brugada syndrome 1	2019-01-31	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	RCV001144227	SCV001304815	uncertain significance	Ventricular fibrillation, paroxysmal familial, type 1	2019-01-31	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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001144228	SCV001304816	benign	Sick sinus syndrome 1	2019-01-31	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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Genetics and Genomics Program, Sidra Medicine	RCV000148863	SCV001434056	uncertain significance	Primary dilated cardiomyopathy		criteria provided, single submitter	research
Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000154845	SCV001984695	likely benign	not specified	2020-12-16	criteria provided, single submitter	clinical testing
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000148863	SCV000089935	not provided	Primary dilated cardiomyopathy		no assertion provided	literature only	This variant has been reported as associated with Dilated cardiomyopathy in the following publications (PMID:21596231). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
CSER _CC_NCGL, University of Washington	RCV000148863	SCV000190607	uncertain significance	Primary dilated cardiomyopathy	2014-06-01	no assertion criteria provided	research