ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.457G>A (p.Val153Met)

gnomAD frequency: 0.00004  dbSNP: rs779074538
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000626664 SCV000747366 uncertain significance Muscle weakness; Hypokalemia; Hypermagnesemia; Myalgia 2017-01-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001860477 SCV002273792 likely pathogenic not provided 2023-11-28 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 153 of the SLC12A3 protein (p.Val153Met). This variant is present in population databases (rs779074538, gnomAD 0.01%). This missense change has been observed in individuals with Gitelman syndrome (PMID: 17654016, 31672324). This variant is also known as c.463G>A, p.Val153Met. ClinVar contains an entry for this variant (Variation ID: 523358). 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%. 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.
MGZ Medical Genetics Center RCV002289914 SCV002580466 uncertain significance Familial hypokalemia-hypomagnesemia 2021-10-25 criteria provided, single submitter clinical testing

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