ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.488C>T (p.Thr163Met)

gnomAD frequency: 0.00001  dbSNP: rs267607050
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001221896 SCV001393965 pathogenic not provided 2023-10-18 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 163 of the SLC12A3 protein (p.Thr163Met). This variant is present in population databases (rs267607050, gnomAD 0.04%). This missense change has been observed in individuals with Gitelman syndrome (PMID: 12112667, 21051746, 26260218, 30596175). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 242798). 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. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001221896 SCV001762016 pathogenic not provided 2021-06-17 criteria provided, single submitter clinical testing
Athena Diagnostics RCV001221896 SCV001879515 pathogenic not provided 2021-05-14 criteria provided, single submitter clinical testing The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant appears to segregate with disease in at least one family, however, the available information does not rule out segregation due to chance. 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.
Genome-Nilou Lab RCV001807148 SCV002055325 pathogenic Familial hypokalemia-hypomagnesemia 2021-07-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001807148 SCV002800679 pathogenic Familial hypokalemia-hypomagnesemia 2021-12-24 criteria provided, single submitter clinical testing
GeneDx RCV001221896 SCV005078664 pathogenic not provided 2024-05-13 criteria provided, single submitter clinical testing Identified as a common variant with an allele frequency of 3.2% in a cohort of 310 Chinese patients diagnosed with Gitelman syndrome (Jiang et al., 2022); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 12112667, 30596175, 35591852, 34389731, 17472852, 25841442, 34604727, 36806220, 19033254, 22679066, 28469853, 21256383, 12686679, 31398183, 17000984, 36158002, 15687331, 34860177, 21051746, 26260218)
Juno Genomics, Hangzhou Juno Genomics, Inc RCV001807148 SCV005417099 pathogenic Familial hypokalemia-hypomagnesemia criteria provided, single submitter clinical testing PM2_Supporting+PP3_Moderate+PM3_VeryStrong+PP1_Strong+PP4
Natera, Inc. RCV001807148 SCV002089327 pathogenic Familial hypokalemia-hypomagnesemia 2021-07-02 no assertion criteria provided clinical testing

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