ClinVar Miner

Submissions for variant NM_001127898.4(CLCN5):c.1249C>T (p.Arg417Ter)

dbSNP: rs797044810
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000381538 SCV000329297 pathogenic not provided 2021-11-30 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 9328929, 24081861, 25907713, 31674016, 25525159, 32683654, 15814539)
Laboratory of Cyto-molecular Genetics, Department of Anatomy, All India Institute of Medical Sciences (AIIMS), New Delhi RCV000192276 SCV002102785 pathogenic Dent disease type 1 2022-03-07 criteria provided, single submitter clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000192276 SCV002768448 pathogenic Dent disease type 1 2020-10-15 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0109 - This gene is known to be associated with X-linked recessive disease. (N) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (exon 11 of 15). (P) 0253 - Variant is hemizygous. (N) 0301 - Variant is absent from gnomAD. (P) 0701 - Comparable variants have very strong previous evidence for pathogenicity. Other variants predicted to cause NMD have been reported as pathogenic (ClinVar; Decipher). (P) 0802 - Moderate previous evidence of pathogenicity in unrelated individuals. The variant has been previously reported in patients with Dent disease (PMID: 24081861, ClinVar, LOVD). (P) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign
Invitae RCV000381538 SCV004299558 pathogenic not provided 2023-06-15 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 207996). This premature translational stop signal has been observed in individual(s) with Dent disease (PMID: 31672324, 31674016). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg347*) 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).
GeneReviews RCV000192276 SCV000243784 not provided Dent disease type 1 no assertion provided literature only

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