ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.1925+1G>A

gnomAD frequency: 0.00002  dbSNP: rs1401379546
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
Baylor Genetics RCV001329193 SCV001520561 pathogenic Familial hypokalemia-hypomagnesemia 2020-04-03 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing [PMID 18391953, 25525159]
Labcorp Genetics (formerly Invitae), Labcorp RCV001863199 SCV002307153 likely pathogenic not provided 2024-02-22 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 15 of the SLC12A3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC12A3 are known to be pathogenic (PMID: 20848653, 22009145, 25841442). This variant is present in population databases (no rsID available, gnomAD 0.008%). Disruption of this splice site has been observed in individual(s) with Gitelman syndrome (PMID: 18391953). ClinVar contains an entry for this variant (Variation ID: 1028204). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Daryl Scott Lab, Baylor College of Medicine RCV001329193 SCV002515378 pathogenic Familial hypokalemia-hypomagnesemia 2022-02-01 criteria provided, single submitter clinical testing
GeneDx RCV001863199 SCV004167651 likely pathogenic not provided 2023-04-17 criteria provided, single submitter clinical testing Identified in patients (phase unknown) with a second variant in the SLC12A3 gene in published literature (Ji et al., 2008); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 18391953)

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.