ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.1196G>T (p.Arg399Leu)

dbSNP: rs13306668
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
GeneDx RCV000439274 SCV000520859 likely pathogenic not provided 2023-01-24 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23328711, 18391953)
Fulgent Genetics, Fulgent Genetics RCV000762973 SCV000893415 likely pathogenic Familial hypokalemia-hypomagnesemia 2021-12-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000439274 SCV001399564 pathogenic not provided 2024-03-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 399 of the SLC12A3 protein (p.Arg399Leu). This variant is present in population databases (rs13306668, gnomAD 0.01%). This missense change has been observed in individuals with Gitelman syndrome (PMID: 18391953, 23328711). ClinVar contains an entry for this variant (Variation ID: 381528). 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 with a positive predictive value of 95%. This variant disrupts the p.Arg399 amino acid residue in SLC12A3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11168953, 17414160, 18391953, 25165177, 26121437). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV000762973 SCV002089347 likely pathogenic Familial hypokalemia-hypomagnesemia 2020-11-24 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.