ClinVar Miner

Submissions for variant NM_001127898.4(CLCN5):c.310C>T (p.Arg104Ter)

dbSNP: rs797044808
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences 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, NCGM 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 (formerly Invitae), Labcorp 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.
GeneReviews RCV000192273 SCV000243781 not provided Dent disease type 1 no assertion provided literature only

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