ClinVar Miner

Submissions for variant NM_001127898.4(CLCN5):c.925C>T (p.Arg309Cys)

gnomAD frequency: 0.00006  dbSNP: rs782056386
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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 RCV000365075 SCV000482538 benign Dent disease type 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV001861353 SCV002226862 uncertain significance not provided 2022-10-07 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 239 of the CLCN5 protein (p.Arg239Cys). This variant is present in population databases (rs782056386, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of CLCN5-related conditions (PMID: 30773290). This variant is also known as c.925C>T (p.Arg309Cys). ClinVar contains an entry for this variant (Variation ID: 368477). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
Yale Center for Mendelian Genomics, Yale University RCV000365075 SCV002106619 likely pathogenic Dent disease type 1 2019-02-14 no assertion criteria provided literature only

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