ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.644T>C (p.Leu215Pro)

gnomAD frequency: 0.00003  dbSNP: rs780594361
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001206570 SCV001377883 pathogenic not provided 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 215 of the SLC12A3 protein (p.Leu215Pro). This variant is present in population databases (rs780594361, gnomAD 0.003%). This missense change has been observed in individuals with Gitelman syndrome (PMID: 9734597, 17329572, 21051746, 26121437). ClinVar contains an entry for this variant (Variation ID: 937539). 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%. Experimental studies have shown that this missense change affects SLC12A3 function (PMID: 12039972, 15102966). For these reasons, this variant has been classified as Pathogenic.
European Hospital Georges Pompidou Genetics Department, Assistance Publique - Hôpitaux de Paris AP-HP RCV001828656 SCV002513794 pathogenic Familial hypokalemia-hypomagnesemia 2022-04-27 criteria provided, single submitter clinical testing ACMG criteria used:PS3, PS4, PM2, PM3, PP3, PP5
Fulgent Genetics, Fulgent Genetics RCV001828656 SCV002810913 pathogenic Familial hypokalemia-hypomagnesemia 2024-02-26 criteria provided, single submitter clinical testing
Natera, Inc. RCV001828656 SCV002089334 pathogenic Familial hypokalemia-hypomagnesemia 2021-01-27 no assertion criteria provided clinical testing

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