ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.1706C>T (p.Ala569Val)

gnomAD frequency: 0.00008  dbSNP: rs79351185
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center RCV000490395 SCV000267499 uncertain significance Familial hypokalemia-hypomagnesemia 2016-03-18 criteria provided, single submitter reference population
Illumina Laboratory Services, Illumina RCV000490395 SCV001273428 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 RCV001753636 SCV001985410 uncertain significance not provided 2019-11-07 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 20981092, 18362449, 10616841, 16966826, 15069170, 26041598, 15198479, 30596175, 32884933, 33348466)
Genome-Nilou Lab RCV000490395 SCV002055364 uncertain significance Familial hypokalemia-hypomagnesemia 2021-07-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000490395 SCV002787803 uncertain significance Familial hypokalemia-hypomagnesemia 2022-05-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001753636 SCV003281508 uncertain significance not provided 2022-03-21 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 569 of the SLC12A3 protein (p.Ala569Val). This variant is present in population databases (rs79351185, gnomAD 0.06%). This missense change has been observed in individuals with Gitelman syndrome (PMID: 20810575, 26041598, 26770037). ClinVar contains an entry for this variant (Variation ID: 225468). 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.

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