ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.1189G>A (p.Val397Met)

gnomAD frequency: 0.00006  dbSNP: rs387907472
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
Fulgent Genetics, Fulgent Genetics RCV002504952 SCV002814489 uncertain significance Familial hypokalemia-hypomagnesemia 2022-04-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000054600 SCV003519453 uncertain significance not provided 2022-07-09 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 397 of the SLC12A3 protein (p.Val397Met). This variant is present in population databases (rs387907472, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SLC12A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 64413). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002515739 SCV003612683 likely benign Inborn genetic diseases 2022-07-05 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Martin Pollak Laboratory, Beth Israel Deaconess Medical Center RCV000054600 SCV000077290 unknown not provided no assertion criteria provided not provided Converted during submission to Uncertain significance.

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.