ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.2186G>T (p.Gly729Val)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV001288429 SCV001475520 pathogenic not provided 2019-10-24 criteria provided, single submitter clinical testing The frequency of this variant in the general population is consistent with pathogenicity. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic.
Invitae RCV001288429 SCV001577607 likely pathogenic not provided 2020-07-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 729 of the SLC12A3 protein (p.Gly729Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs373901523, ExAC 0.03%). This variant has been observed in individual(s) with Gitelman syndrome (PMID: 17654016, 11168953, 31672324). 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 variant disrupts the p.Gly729 amino acid residue in SLC12A3. Other variant(s) that disrupt this residue have been observed in individuals with SLC12A3-related conditions (PMID: 21415153), which suggests that this may be a clinically significant amino acid residue. 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.

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