ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.472C>T (p.Arg158Trp)

gnomAD frequency: 0.00001  dbSNP: rs1041531529
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000993006 SCV001145679 uncertain significance not provided 2019-06-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000993006 SCV002248285 likely pathogenic not provided 2023-02-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 158 of the SLC12A3 protein (p.Arg158Trp). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with Gitelman syndrome (PMID: 31285285). ClinVar contains an entry for this variant (Variation ID: 805471). 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.Arg158 amino acid residue in SLC12A3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12112667, 21415153, 25852896, 30413979). 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.
Natera, Inc. RCV001832310 SCV002089326 uncertain significance Familial hypokalemia-hypomagnesemia 2021-03-13 no assertion criteria provided clinical testing

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