ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.1489A>T (p.Lys497Ter)

gnomAD frequency: 0.00002  dbSNP: rs746818109
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001056876 SCV001221341 pathogenic not provided 2023-11-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys497*) 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 (rs746818109, gnomAD 0.004%). This premature translational stop signal has been observed in individuals with Gitelman syndrome (PMID: 11168953). ClinVar contains an entry for this variant (Variation ID: 852297). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001276375 SCV005395697 pathogenic Familial hypokalemia-hypomagnesemia 2024-09-05 criteria provided, single submitter clinical testing Variant summary: SLC12A3 c.1489A>T (p.Lys497X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.7e-05 in 230414 control chromosomes (gnomAD). c.1489A>T has been reported in the literature in at least an individual affected with Gitelman Syndrome (Palazzo_2022). The following publication has been ascertained in the context of this evaluation (PMID: 35628451). ClinVar contains an entry for this variant (Variation ID: 852297). Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc. RCV001276375 SCV001462610 pathogenic Familial hypokalemia-hypomagnesemia 2020-09-16 no assertion criteria provided clinical testing

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