Submissions for variant NM_000335.5(SCN5A):c.1236C>T (p.Val412=)

gnomAD frequency: 0.00114  dbSNP: rs45565936

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000151797	SCV000171555	benign	not specified	2014-02-14	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000151797	SCV000200259	benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.Val412Val in Exon 10 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 0.5% (18/3456) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs45565936).
Invitae	RCV000713132	SCV000557130	benign	not provided	2024-01-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621879	SCV000735631	likely benign	Cardiovascular phenotype	2016-08-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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	RCV000713132	SCV000843703	benign	not provided	2018-02-20	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000151797	SCV000918191	benign	not specified	2018-05-29	criteria provided, single submitter	clinical testing	Variant summary: SCN5A c.1236C>T alters a non-conserved nucleotide resulting in a synonymous change. The variant allele was found at a frequency of 0.00035 in 277196 control chromosomes. The observed variant frequency within African control individuals in the gnomAD database is approximately 140 fold of the estimated maximal expected allele frequency for a pathogenic variant in SCN5A causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.1236C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Color Diagnostics, LLC DBA Color Health	RCV001842443	SCV001342464	benign	Cardiac arrhythmia	2018-12-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000713132	SCV002049929	likely benign	not provided	2021-02-04	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001842443	SCV004822725	benign	Cardiac arrhythmia	2024-02-05	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000151797	SCV001924774	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000713132	SCV001957813	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000713132	SCV001964613	likely benign	not provided		no assertion criteria provided	clinical testing