ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.1046C>T (p.Pro349Leu)

gnomAD frequency: 0.00001  dbSNP: rs121909383
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000820759 SCV000961486 pathogenic not provided 2024-12-29 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 349 of the SLC12A3 protein (p.Pro349Leu). This variant is present in population databases (rs121909383, gnomAD 0.007%). This missense change has been observed in individuals with Gitelman's syndrome (PMID: 8528245, 8900229, 21415153). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 8592). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SLC12A3 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000009123 SCV002811075 pathogenic Familial hypokalemia-hypomagnesemia 2024-01-05 criteria provided, single submitter clinical testing
OMIM RCV000009123 SCV000029340 pathogenic Familial hypokalemia-hypomagnesemia 1996-01-01 no assertion criteria provided literature only
Natera, Inc. RCV000009123 SCV002089340 likely pathogenic Familial hypokalemia-hypomagnesemia 2021-03-18 no assertion criteria provided clinical testing

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