ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.3026G>A (p.Arg1009Gln)

gnomAD frequency: 0.00004  dbSNP: rs370175770
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000729474 SCV000857141 pathogenic not provided 2017-09-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000729474 SCV001590625 pathogenic not provided 2024-01-07 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1018 of the SLC12A3 protein (p.Arg1018Gln). This variant is present in population databases (rs370175770, gnomAD 0.008%). This missense change has been observed in individual(s) with Gitelman syndrome (PMID: 17511264, 21415153, 22009145, 23328711). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 594235). 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%. This variant disrupts the p.Arg1018 amino acid residue in SLC12A3. Other variant(s) that disrupt this residue have been observed in individuals with SLC12A3-related conditions (PMID: 23328711), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV001807339 SCV002055360 pathogenic Familial hypokalemia-hypomagnesemia 2021-07-15 criteria provided, single submitter clinical testing
Natera, Inc. RCV001807339 SCV002089382 pathogenic Familial hypokalemia-hypomagnesemia 2021-06-29 no assertion criteria provided clinical testing

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