Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Fulgent Genetics, |
RCV002480886 | SCV002793646 | likely pathogenic | Dent disease type 1; Hypophosphatemic rickets, X-linked recessive; X-linked recessive nephrolithiasis with renal failure; Proteinuria, low molecular weight, with hypercalciuria and nephrocalcinosis | 2021-12-28 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003558785 | SCV004299557 | likely pathogenic | not provided | 2023-04-06 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this missense change affects CLCN5 function (PMID: 19657328, 22083641, 23566014). 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. ClinVar contains an entry for this variant (Variation ID: 988249). This missense change has been observed in individual(s) with Dent disease (PMID: 15086899, 15895257, 25907713). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 221 of the CLCN5 protein (p.Cys221Arg). |
| Sydney Genome Diagnostics, |
RCV001328283 | SCV001449233 | likely pathogenic | Nephrotic syndrome | 2019-05-28 | no assertion criteria provided | clinical testing | This individual is hemizygous for the c.661T>C variant in the CLCN5 gene, which results in the amino acid substitution of cysteine to arginine at residue 221, p.(Cys221Arg). This variant has been reported in an individual with Dent'ss disease (Hoopes et al Kidney Int. 2004 May;65(5):1615-20). Functional studies showed that this variant interferred with channel function and abolished trafficking to the plasma membrane (Ludwig et al Hum Genet. 2005 Jul;117(2-3):228-37). The variant has not been reported in any population databases (i.e. gnomAD, ExAC, ESP or dbSNP). In silico analysis of pathogenicity (through Alamut Visual v2.8.1) using PolyPhen2, SIFT and MutationTaster all suggest that this variant is likely to be pathogenic. However, this analysis alone cannot be used to confirm pathogenicity. This variant is considered to be likely pathogenic according to the ACMG guidelines (Evidence used: PS3, PM2, PP3, PP5). |