Submissions for variant NM_006514.4(SCN10A):c.1534C>G (p.Arg512Gly)

dbSNP: rs200714519

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	RCV000496453	SCV000588145	uncertain significance	Brugada syndrome	2017-02-14	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000622755	SCV000740412	uncertain significance	not specified	2017-07-26	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV001262794	SCV001440796	uncertain significance	Episodic pain syndrome, familial, 2	2019-01-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001565417	SCV001788756	uncertain significance	not provided	2019-08-02	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496453	SCV002290470	uncertain significance	Brugada syndrome	2021-10-31	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 512 of the SCN10A protein (p.Arg512Gly). This variant is present in population databases (rs200714519, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. ClinVar contains an entry for this variant (Variation ID: 431375). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV004023323	SCV003702457	uncertain significance	Cardiovascular phenotype	2023-07-31	criteria provided, single submitter	clinical testing	The p.R512G variant (also known as c.1534C>G), located in coding exon 11 of the SCN10A gene, results from a C to G substitution at nucleotide position 1534. The arginine at codon 512 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004735571	SCV005350622	uncertain significance	SCN10A-related disorder	2024-03-12	no assertion criteria provided	clinical testing	The SCN10A c.1534C>G variant is predicted to result in the amino acid substitution p.Arg512Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.