Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001938033 | SCV002183914 | uncertain significance | not provided | 2021-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with valine at codon 201 of the SLC12A3 protein (p.Gly201Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with Gitelman syndrome (PMID: 21415153, 31672324; Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). |
| European Hospital Georges Pompidou Genetics Department, |
RCV002243481 | SCV002513792 | likely pathogenic | Familial hypokalemia-hypomagnesemia | 2022-04-27 | criteria provided, single submitter | clinical testing | ACMG criteria used:PM1, PM2, PP3, PP5 |