ClinVar Miner

Submissions for variant NM_001127898.4(CLCN5):c.1025A>G (p.Tyr342Cys)

dbSNP: rs273585644
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002514143 SCV003444661 likely pathogenic not provided 2023-10-06 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 272 of the CLCN5 protein (p.Tyr272Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Dent disease (PMID: 16822791, 24081861, 31328266, 31674016). This variant is also known as c.1025A>G (p.Y342C). ClinVar contains an entry for this variant (Variation ID: 40985). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects CLCN5 function (PMID: 21305656). This variant disrupts the p.Tyr272 amino acid residue in CLCN5. Other variant(s) that disrupt this residue have been observed in individuals with CLCN5-related conditions (PMID: 24081861), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneReviews RCV000033877 SCV000057785 not provided Dent disease type 1 no assertion provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.