ClinVar Miner

Submissions for variant NM_001127898.4(CLCN5):c.1A>G (p.Met1Val)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002472296 SCV002769432 uncertain significance Dent disease type 1 2021-05-06 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. The following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Dent disease (MIM#300009), hypophosphatemic rickets (MIM#300554), nephrolithiasis type I (MIM#310468) and low molecular weight proteinuria with hypercalciuria and nephrocalcinosis (MIM#308990). (I) 0109 - This gene is associated with X-linked recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity, with intra- and inter-familial phenotypic variability previously reported (PMID: 28580211, OMIM). (I) 0207 - Variant is predicted to result in a loss of the canonical translation initiation codon (ATG) however, CLCN5 has alternative 5’UTR exons which results in multiple transcripts and isoforms with alternative start sites (PMID: 25001568). (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 0705 - No other start-loss variants have previous evidence for pathogenicity. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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