Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Prevention |
RCV003417691 | SCV004112947 | pathogenic | CLCN5-related disorder | 2022-12-07 | criteria provided, single submitter | clinical testing | The CLCN5 c.100C>T variant is predicted to result in premature protein termination (p.Arg34*). This variant has been reported to have occurred de novo or be inherited from a mother with nephrolithiasis in two hemizygous patients with Dent disease (Hoopes et al. 1998. PubMed ID: 9734595; Wen et al. 2018. PubMed ID: 30581818). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in CLCN5 are expected to be pathogenic. This variant is interpreted as pathogenic. |
Neuberg Centre For Genomic Medicine, |
RCV004546452 | SCV005042922 | likely pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | criteria provided, single submitter | clinical testing | The stop gained c.310C>Tp.Arg104Ter variant in CLCN5 gene has reported in hemizygous state in an individual affected with CLCN5 related disorders Wen M, et. al., 2018. The c.310C>T variant is novel not in any individuals in gnomAD Exomes and 1000Genomes. This variant has been reported to the ClinVar database. The nucleotide change c.310C>T in CLCN5 is predicted asconserved by GERP++ and PhyloP across 100 vertebrates. Loss of function variants have been previously reported to be diseasecausing. For these reasons, this variant has been classified as Likely Pathogenic. | |
Labcorp Genetics |
RCV005089965 | SCV005842266 | pathogenic | not provided | 2025-01-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg34*) in the CLCN5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLCN5 are known to be pathogenic (PMID: 22876375, 25907713). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with X-linked nephrolithiasis (PMID: 9734595). ClinVar contains an entry for this variant (Variation ID: 207994). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000192273 | SCV000243781 | not provided | Dent disease type 1 | no assertion provided | literature only |