ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.514T>C (p.Trp172Arg)

gnomAD frequency: 0.00001  dbSNP: rs757792232
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001702309 SCV002245987 pathogenic not provided 2021-12-03 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt SLC12A3 protein function. ClinVar contains an entry for this variant (Variation ID: 1285185). This missense change has been observed in individuals with Gitelman syndrome (PMID: 12112667). This variant is present in population databases (rs757792232, gnomAD 0.0009%). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 172 of the SLC12A3 protein (p.Trp172Arg).
European Hospital Georges Pompidou Genetics Department, Assistance Publique - Hôpitaux de Paris AP-HP RCV002243433 SCV002513869 likely pathogenic Familial hypokalemia-hypomagnesemia 2022-04-27 criteria provided, single submitter clinical testing ACMG criteria used:PS4, PM1, PM2, PM3, PP5
GeneDx RCV001702309 SCV003842447 pathogenic not provided 2023-03-15 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25841442, 14596636, Portioli2021[review], 22009145, 34426522, 31672324, 12112667)
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001702309 SCV001929519 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001702309 SCV001958463 pathogenic not provided no assertion criteria provided clinical testing

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.