ClinVar Miner

Submissions for variant NM_000338.3(SLC12A1):c.760C>G (p.Pro254Ala)

dbSNP: rs367562995
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001121892 SCV001280547 uncertain significance Bartter disease type 1 2017-09-06 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.
Fulgent Genetics, Fulgent Genetics RCV001121892 SCV002776760 uncertain significance Bartter disease type 1 2022-02-17 criteria provided, single submitter clinical testing
Invitae RCV002558206 SCV003442863 uncertain significance not provided 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 254 of the SLC12A1 protein (p.Pro254Ala). This variant is present in population databases (rs367562995, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SLC12A1-related conditions. This variant is also known as P250A. ClinVar contains an entry for this variant (Variation ID: 888525). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change does not substantially affect SLC12A1 function (PMID: 21157372, 21209010). 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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