Submissions for variant NM_000335.5(SCN5A):c.3266C>T (p.Pro1089Leu)

gnomAD frequency: 0.00071  dbSNP: rs1805125

Total submissions: 22

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000041614	SCV000050839	benign	not specified	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041614	SCV000065310	likely benign	not specified	2012-11-05	criteria provided, single submitter	clinical testing	Pro1090Leu in exon 18 of SCN5A: This variant is not expected to have clinical si gnificance because it has been identified in 2.1% (12/572) of chromosomes from a broad, though clinically and racially unspecified population from 1000 Genomes Project (http://1000genomes.org; rs1805125). Pro1090Leu in exon 18 of SCN5A (r s1805125; allele frequency = 2.1%, 12/572)
GeneDx	RCV000041614	SCV000171566	benign	not specified	2011-11-30	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.
Invitae	RCV000058559	SCV000291798	benign	not provided	2024-01-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000242258	SCV000318823	benign	Cardiovascular phenotype	2015-03-25	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.
Color Diagnostics, LLC DBA Color Health	RCV001841602	SCV000902961	benign	Cardiac arrhythmia	2018-03-19	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852963	SCV000995712	likely benign	Hypertrophic cardiomyopathy	2018-05-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001149367	SCV001310316	likely benign	Ventricular fibrillation, paroxysmal familial, type 1	2018-05-09	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	RCV001149368	SCV001310317	likely benign	Long QT syndrome 3	2018-05-09	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	RCV001149369	SCV001310318	likely benign	Brugada syndrome 1	2018-05-09	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	RCV001149370	SCV001310319	likely benign	Dilated cardiomyopathy 1E	2018-05-09	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	RCV001149371	SCV001310320	benign	Sick sinus syndrome 1	2018-05-09	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	RCV001149372	SCV001310321	likely benign	Progressive familial heart block, type 1A	2018-05-09	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.
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV001084763	SCV001338813	benign	Brugada syndrome	2019-05-17	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002483030	SCV002797349	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	2022-05-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000058559	SCV004033983	benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	SCN5A: PP3, BS1, BS2
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000058559	SCV004563062	likely benign	not provided	2023-11-09	criteria provided, single submitter	clinical testing
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058559	SCV000090079	not provided	not provided		no assertion provided	literature only	This variant has been reported in the following publications (PMID:10807545;PMID:15689442;PMID:16155735;PMID:18426444;PMID:19841300;PMID:20129283).
Clinical Genetics, Academic Medical Center	RCV000041614	SCV001920603	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000041614	SCV001928174	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000041614	SCV001953296	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000058559	SCV001974458	likely benign	not provided		no assertion criteria provided	clinical testing