ClinVar Miner

Submissions for variant NM_003098.3(SNTA1):c.566C>T (p.Ser189Leu)

gnomAD frequency: 0.00020  dbSNP: rs144860423
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000251711 SCV000318682 likely benign Cardiovascular phenotype 2022-03-28 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587989 SCV000698166 likely benign not provided 2016-04-26 criteria provided, single submitter clinical testing Variant summary: The c.566C>T in SNTA1 gene is a missense change that alters a highly conserved nucleotide and 3/4 in silico tools predict deleterious outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.02%, predominantly in individuals of European descent (0.03%). These frequencies exceed the maximal expected allele frequency for a pathogenic variant in SNTA1 gene (0.001%). The variant of interest has not, to our knowledge, been reported in affected individuals in published reports or cited by a reputable database/diagnostic center. Taking together, the variant was classified as Likely Benign.
Illumina Laboratory Services, Illumina RCV000624991 SCV001303915 uncertain significance Long QT syndrome 12 2018-03-30 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV001213908 SCV001385564 uncertain significance Long QT syndrome 2023-12-24 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 189 of the SNTA1 protein (p.Ser189Leu). This variant is present in population databases (rs144860423, gnomAD 0.04%). This missense change has been observed in individual(s) with atrial fibrillation, arrhythmogenic right ventricular cardiomyopathy, sudden infant death syndrome, and sudden cardiac arrest (PMID: 28074886, 28837624, 30847666, 30975432). ClinVar contains an entry for this variant (Variation ID: 263623). 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 SNTA1 protein function with a negative predictive value of 80%. 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 RCV000587989 SCV001771674 uncertain significance not provided 2021-01-04 criteria provided, single submitter clinical testing Variant has been reported in the literature in patients with lone atrial fibrillation, unspecified arrhythmia, ARVC, and/or sudden cardiac death, most of whom also harbored additional cardiac variants thought to contribute to disease (Husser et al., 2017; Proost et al., 2017, van Lint et al., 2019); Reported in ClinVar but additional evidence is not available (ClinVar Variant ID #263623; Landrum et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30847666, 28837624, 28341588)

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.