Submissions for variant NM_000335.5(SCN5A):c.5709G>A (p.Ser1903=)

gnomAD frequency: 0.00034  dbSNP: rs376826051

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000588185	SCV000557105	benign	not provided	2025-01-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588185	SCV000700041	benign	not provided	2016-11-28	criteria provided, single submitter	clinical testing	Variant summary: The SCN5A c.5712G>A (p.Ser1904=) variant causes a synonymous change that involves a non-conserved nucleotide. 4/5 splice in silico tools predict no significant impact on normal splicing and ESE finder predicts alterations to ESE binding, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 71/120770 (1/1700), predominantly in individuals of Latino descent, 61/11576 (1/189), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic SCN5A variant of 1/40000. Therefore, it is likely that the variant of interest is an ethnic specific polymorphism. The c.5712G>A has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as Benign.
Ambry Genetics	RCV000619919	SCV000737731	likely benign	Cardiovascular phenotype	2016-09-26	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.
Color Diagnostics, LLC DBA Color Health	RCV001841384	SCV000903391	benign	Cardiac arrhythmia	2018-04-07	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV001195212	SCV001365518	likely benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.Ser1904Ser in Exon 28 of SCN5A: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located within the splice consensus sequence. It has been identified in 0.1% (2/3562) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS;).
GeneDx	RCV000588185	SCV001944469	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588185	SCV004564925	likely benign	not provided	2023-10-14	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001841384	SCV004821404	benign	Cardiac arrhythmia	2024-02-05	criteria provided, single submitter	clinical testing