ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.482G>A (p.Trp161Ter)

gnomAD frequency: 0.00006  dbSNP: rs201190064
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001208463 SCV001379853 pathogenic not provided 2024-12-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp161*) in the SLC12A3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC12A3 are known to be pathogenic (PMID: 20848653, 22009145, 25841442). This variant is present in population databases (rs201190064, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with Gitelman syndrome (PMID: 19349556). ClinVar contains an entry for this variant (Variation ID: 939124). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001208463 SCV001787406 pathogenic not provided 2023-05-31 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 19349556)
Genome-Nilou Lab RCV001807392 SCV002055323 pathogenic Familial hypokalemia-hypomagnesemia 2021-07-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001807392 SCV002811099 pathogenic Familial hypokalemia-hypomagnesemia 2024-01-15 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001807392 SCV005203802 pathogenic Familial hypokalemia-hypomagnesemia 2024-07-02 criteria provided, single submitter clinical testing Variant summary: SLC12A3 c.482G>A (p.Trp161X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 1.2e-05 in 249686 control chromosomes, predominantly at a frequency of 2.7e-05 within the Non-Finnish European subpopulation in the gnomAD database. c.482G>A has been reported in the literature in at-least one individual affected with Gitelman Syndrome (example, Roser_2009). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 19349556). ClinVar contains an entry for this variant (Variation ID: 939124). Based on the evidence outlined above, the variant was classified as pathogenic.

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