ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.1844C>G (p.Ser615Trp)

dbSNP: rs779160677
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues RCV001801295 SCV002047504 likely pathogenic Familial hypokalemia-hypomagnesemia 2021-07-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002541347 SCV003443529 likely pathogenic not provided 2022-04-26 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 615 of the SLC12A3 protein (p.Ser615Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SLC12A3-related conditions (PMID: 12112667). ClinVar contains an entry for this variant (Variation ID: 1330263). 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. This variant disrupts the p.Ser615 amino acid residue in SLC12A3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11168953, 20552229, 22728489, 27303630, 30596175). 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.

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