Submissions for variant NM_000335.5(SCN5A):c.1587T>C (p.Ile529=)

gnomAD frequency: 0.00575  dbSNP: rs45624133

Total submissions: 22

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041602	SCV000065298	benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.Ile529Ile in Exon 12 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 0.9% (58/6814) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs45624133).
Invitae	RCV000586395	SCV000291781	benign	not provided	2024-01-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000041602	SCV000306536	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000245011	SCV000317779	benign	Cardiovascular phenotype	2014-12-18	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586395	SCV000700014	benign	not provided	2016-02-22	criteria provided, single submitter	clinical testing	Variant summary: Variant affects a non-conserved nucleotide and results in a synonymous mutation. 5/5 in silico prediction tools via Alamut predict the variant not to have an effect on normal splicing and while mutation taster predicts the variant to be disease causing. The variant was found predominantly in the Finnish European subcohort of the ExAC project at an allele frequency of 1.5% indicating the variant to be a neutral polymorphism in individuals of Finnish origin. Moreover, a publication (Garca-Molina_ClinGen_2013) and a clinical diagnostic laboratory via ClinVar classifies variant as polymorphism/Benign. Considering all evidence, the variant was classified as Benign.
Athena Diagnostics	RCV000586395	SCV000843707	benign	not provided	2017-11-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001841591	SCV000902705	benign	Cardiac arrhythmia	2018-03-08	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000586395	SCV001157031	benign	not provided	2023-08-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001150021	SCV001311028	likely benign	Brugada syndrome 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001150022	SCV001311029	likely benign	Dilated cardiomyopathy 1E	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001150023	SCV001311030	likely benign	Ventricular fibrillation, paroxysmal familial, type 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001150024	SCV001311031	likely benign	Progressive familial heart block, type 1A	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001150025	SCV001311032	likely benign	Sick sinus syndrome 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001150026	SCV001311033	likely benign	Long QT syndrome 3	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000586395	SCV001371045	likely benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	SCN5A: BP4, BP7, BS2
GeneDx	RCV000586395	SCV001839569	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486623	SCV004239651	benign	Cardiomyopathy	2022-11-16	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001841591	SCV004822704	benign	Cardiac arrhythmia	2024-02-05	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000586395	SCV001744381	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000041602	SCV001918066	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000041602	SCV001951968	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000041602	SCV001975531	benign	not specified		no assertion criteria provided	clinical testing