Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Fulgent Genetics, |
RCV000762974 | SCV000893417 | pathogenic | Familial hypokalemia-hypomagnesemia | 2022-03-09 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000681801 | SCV001202771 | pathogenic | not provided | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 731 of the SLC12A3 protein (p.Gly731Arg). This variant is present in population databases (rs752101663, gnomAD 0.004%). This missense change has been observed in individual(s) with Gitelman syndrome (PMID: 8900229, 12112667, 21415153, 25422309). 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: 562347). 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: 27582097). For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000762974 | SCV002055348 | pathogenic | Familial hypokalemia-hypomagnesemia | 2021-07-15 | criteria provided, single submitter | clinical testing | |
European Hospital Georges Pompidou Genetics Department, |
RCV000762974 | SCV002513815 | pathogenic | Familial hypokalemia-hypomagnesemia | 2022-04-27 | criteria provided, single submitter | clinical testing | ACMG criteria used:PS3, PS4, PM1, PM2, PM3, PP3, PP5 |
Division Of Personalized Genomic Medicine, |
RCV000762974 | SCV004190151 | likely pathogenic | Familial hypokalemia-hypomagnesemia | 2020-04-13 | criteria provided, single submitter | clinical testing | The c.2191G>A variant in the SLC12A3 gene is a heterozygous missense variant, which results in the substitution of the highly conserved glycine residue at the 731 position to arginine (p.Gly731Arg). This variant localizes to coding exon 18 of the SLC12A3 gene (26 exons total; NM_000339.3). This variant is predicted to be deleterious and damaging to protein structure and/or function based on in silico analyses (PROVEAN and SIFT). This variant has been observed in the Genome Aggregation Database (gnomAD) at a very low frequency (allele frequency = 0.00002837, no homozygotes), indicating it is not a common benign variant in the populations represented in this database. This variant has been reported in multiple individuals with Gitelman syndrome either in the homozygous state or with another SLC12A3 variant (PMIDs: 17699451, 21415153, 30596175, 25422309). |
Gharavi Laboratory, |
RCV000681801 | SCV000809268 | likely pathogenic | not provided | 2018-09-16 | no assertion criteria provided | research | |
Natera, |
RCV000762974 | SCV002089371 | pathogenic | Familial hypokalemia-hypomagnesemia | 2020-09-30 | no assertion criteria provided | clinical testing |