ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.1388G>A (p.Gly463Glu)

gnomAD frequency: 0.00001  dbSNP: rs1375515522
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001980278 SCV002271087 likely pathogenic not provided 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 463 of the SLC12A3 protein (p.Gly463Glu). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with SLC12A3-related conditions (PMID: 12112667). ClinVar contains an entry for this variant (Variation ID: 1488711). 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.Gly463 amino acid residue in SLC12A3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27582097, 31672324). 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.
European Hospital Georges Pompidou Genetics Department, Assistance Publique - Hôpitaux de Paris AP-HP RCV002243499 SCV002513805 likely pathogenic Familial hypokalemia-hypomagnesemia 2022-04-27 criteria provided, single submitter clinical testing ACMG criteria used:PM1, PM2 PM5, PP3, PP5
Fulgent Genetics, Fulgent Genetics RCV002243499 SCV002797163 likely pathogenic Familial hypokalemia-hypomagnesemia 2022-03-05 criteria provided, single submitter clinical testing

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