Submissions for variant NM_000335.5(SCN5A):c.630G>A (p.Val210=)

gnomAD frequency: 0.00064  dbSNP: rs193922727

Total submissions: 21

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000151806	SCV000171545	benign	not specified	2015-03-17	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	RCV000151806	SCV000200272	likely benign	not specified	2015-05-27	criteria provided, single submitter	clinical testing	p.Val210Val in exon 6 of SCN5A: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.1% (42/41192) of European chromosomes from by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org/; dbSNP rs193922727).
Invitae	RCV000757740	SCV000291829	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000620296	SCV000735567	likely benign	Cardiovascular phenotype	2016-10-25	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757740	SCV000886079	benign	not provided	2022-10-20	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001841552	SCV000903650	likely benign	Cardiac arrhythmia	2018-08-27	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001149163	SCV001310101	uncertain significance	Dilated cardiomyopathy 1E	2018-05-31	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	RCV001150667	SCV001311755	uncertain significance	Progressive familial heart block, type 1A	2018-05-31	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	RCV001150668	SCV001311756	uncertain significance	Ventricular fibrillation, paroxysmal familial, type 1	2018-05-31	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001150669	SCV001311757	uncertain significance	Sick sinus syndrome 1	2018-05-31	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	RCV001150670	SCV001311758	likely benign	Long QT syndrome 3	2018-05-31	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	RCV001150671	SCV001311759	uncertain significance	Brugada syndrome 1	2018-05-31	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000030445	SCV004239688	likely benign	Cardiomyopathy	2023-02-21	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001841552	SCV004823234	likely benign	Cardiac arrhythmia	2024-02-05	criteria provided, single submitter	clinical testing
Roden Lab, Vanderbilt University Medical Center	RCV001150671	SCV005200428	uncertain significance	Brugada syndrome 1		criteria provided, single submitter	research	We classified this variant using data from the calibrated functional assay 'ParSE-seq' (PMID: 37732247), population data, and in silico data within the ACMG v3 framework (PMID: 25741868)The SCN5A variant, 3-38613816-C-T was evaluated for association with the loss-of-function condition Brugada Syndrome.This Variant had an AF of 0.000605048 in gnomAD v3The in silico predictor SpliceAI scored the variant as 0.27; normal <0.2, likely damaging >0.5.Using the functional RNA-splicing assay, ParSE-seq, the variant was evaluated to have a strong negative impact on splicing (PS3_strong) following the Brnich et al. calibration framework (PMID: 31892348). In aggregate, we therefore classify this variant as VUS using these collective data.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030445	SCV000053114	benign	Cardiomyopathy	2015-06-12	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000757740	SCV001743694	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000151806	SCV001920989	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000757740	SCV001930471	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000757740	SCV001959727	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000757740	SCV001969877	likely benign	not provided		no assertion criteria provided	clinical testing