ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.626G>C (p.Arg209Pro)

dbSNP: rs758035631
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002020283 SCV002290843 likely pathogenic not provided 2023-11-10 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 209 of the SLC12A3 protein (p.Arg209Pro). This variant is present in population databases (rs758035631, gnomAD 0.0009%). This missense change has been observed in individual(s) with Gitelman syndrome (PMID: 30596175). ClinVar contains an entry for this variant (Variation ID: 1505020). 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.Arg209 amino acid residue in SLC12A3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11168953, 21415153, 23328711; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Fulgent Genetics, Fulgent Genetics RCV002498026 SCV002809115 likely pathogenic Familial hypokalemia-hypomagnesemia 2021-10-14 criteria provided, single submitter clinical testing

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