ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.2850_2851del (p.Arg950fs)

dbSNP: rs746623621
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 RCV001053105 SCV001217348 pathogenic not provided 2024-01-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg959Serfs*11) in the SLC12A3 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 72 amino acid(s) of the SLC12A3 protein. This variant is present in population databases (rs746623621, gnomAD 0.05%). This premature translational stop signal has been observed in individual(s) with Gitelman disease (PMID: 14750096, 27529443, 30138938, 30596175). 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: 849196). This variant disrupts a region of the SLC12A3 protein in which other variant(s) (p.Arg1018*) have been determined to be pathogenic (PMID: 12911530, 26770037, 29942493). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
3billion RCV001832488 SCV002573385 pathogenic Familial hypokalemia-hypomagnesemia 2022-09-01 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: 0.004%). It is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with SLC12A3 -related disorder (ClinVar ID: VCV000849196/ PMID: 14750096). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Fulgent Genetics, Fulgent Genetics RCV001832488 SCV002811701 pathogenic Familial hypokalemia-hypomagnesemia 2022-03-03 criteria provided, single submitter clinical testing
OMIM RCV001832488 SCV000029345 pathogenic Familial hypokalemia-hypomagnesemia 2006-09-26 no assertion criteria provided literature only
Natera, Inc. RCV001832488 SCV002089379 pathogenic Familial hypokalemia-hypomagnesemia 2020-12-03 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.