ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.3521A>G (p.Tyr1174Cys)

gnomAD frequency: 0.00001  dbSNP: rs1167279918
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000691060 SCV000818799 uncertain significance Brugada syndrome 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1174 of the SCN10A protein (p.Tyr1174Cys). This variant is not present in population databases (gnomAD no frequency). 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: 570243). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SCN10A protein function. 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.
GeneDx RCV003226968 SCV003923779 uncertain significance not provided 2022-11-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV003303127 SCV004000486 uncertain significance Cardiovascular phenotype 2023-03-16 criteria provided, single submitter clinical testing The p.Y1174C variant (also known as c.3521A>G), located in coding exon 20 of the SCN10A gene, results from an A to G substitution at nucleotide position 3521. The tyrosine at codon 1174 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GenomeConnect - Invitae Patient Insights Network RCV001535722 SCV001749816 not provided Episodic pain syndrome, familial, 2 no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 11-24-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.