ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.2470T>A (p.Ser824Thr)

gnomAD frequency: 0.00038  dbSNP: rs146845953
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000516874 SCV000615288 uncertain significance not specified 2017-05-09 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001115549 SCV001273532 uncertain significance Familial hypokalemia-hypomagnesemia 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx RCV000782230 SCV001819753 uncertain significance not provided 2024-05-02 criteria provided, single submitter clinical testing Reported in the heterozygous state in an individual with Gitelman syndrome, but a second SLC12A3 variant was not identified in this individual (PMID: 22009145); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25841442, 34604727, 22009145)
Genome-Nilou Lab RCV001115549 SCV002055365 uncertain significance Familial hypokalemia-hypomagnesemia 2021-07-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000782230 SCV003293820 uncertain significance not provided 2022-08-19 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 833 of the SLC12A3 protein (p.Ser833Thr). This variant is present in population databases (rs146845953, gnomAD 0.07%). This missense change has been observed in individual(s) with clinical features of Gitelman syndrome (PMID: 22009145). ClinVar contains an entry for this variant (Variation ID: 448393). 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 not expected to disrupt SLC12A3 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Gharavi Laboratory, Columbia University RCV000782230 SCV000920719 uncertain significance not provided 2018-09-16 no assertion criteria provided research
Natera, Inc. RCV001115549 SCV002089372 uncertain significance Familial hypokalemia-hypomagnesemia 2020-01-14 no assertion criteria provided clinical testing

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