ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.539C>A (p.Thr180Lys)

gnomAD frequency: 0.00003  dbSNP: rs146158333
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 RCV000803323 SCV000943187 pathogenic not provided 2024-11-14 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 180 of the SLC12A3 protein (p.Thr180Lys). This variant is present in population databases (rs146158333, gnomAD 0.4%). This missense change has been observed in individual(s) with Gitelman syndrome (PMID: 10616841, 21628937, 21757836, 26041598). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 648571). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC12A3 protein function. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV001115368 SCV002055285 likely pathogenic Familial hypokalemia-hypomagnesemia 2021-07-15 criteria provided, single submitter clinical testing
3billion, Medical Genetics RCV001115368 SCV002521201 likely pathogenic Familial hypokalemia-hypomagnesemia 2022-05-22 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.025%). Missense changes are a common disease-causing mechanism. Same nucleotide change resulting in same amino acid change has been previously reported to be associated with SLC12A3 related disorder (ClinVar ID: VCV000648571 / PMID: 10616841). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 26041598) and to co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated family (PMID:10616841). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Fulgent Genetics, Fulgent Genetics RCV001115368 SCV005639176 pathogenic Familial hypokalemia-hypomagnesemia 2024-06-19 criteria provided, single submitter clinical testing
Natera, Inc. RCV001115368 SCV002089329 pathogenic Familial hypokalemia-hypomagnesemia 2021-02-23 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.