ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.2599G>A (p.Gly867Ser)

gnomAD frequency: 0.00003  dbSNP: rs370301695
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001756536 SCV001985414 uncertain significance not provided 2021-04-26 criteria provided, single submitter clinical testing Observed in a patient with Gitelman syndrome in published literature (Fava et al., 2007); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 17654016)
Labcorp Genetics (formerly Invitae), Labcorp RCV001756536 SCV002307547 likely pathogenic not provided 2024-05-14 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 876 of the SLC12A3 protein (p.Gly876Ser). This variant is present in population databases (rs370301695, gnomAD 0.01%). This missense change has been observed in individuals with Gitelman syndrome (PMID: 17654016; Invitae). ClinVar contains an entry for this variant (Variation ID: 1303037). 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 80%. 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 RCV002243457 SCV002513822 likely pathogenic Familial hypokalemia-hypomagnesemia 2022-04-27 criteria provided, single submitter clinical testing ACMG criteria used:PM1 PM2 PM3 PP5

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