Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV004595115 | SCV005087209 | uncertain significance | Familial juvenile hyperuricemic nephropathy type 1 | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0104 - Dominant negative is a known mechanism of disease in this gene and is associated with UMOD-related tubulointerstitial kidney disease, familial juvenile hyperuricemic nephropathy 1 (MIM#162000), glomerulocystic kidney disease with hyperuricemia and isosthenuria (MIM#609886) and medullary cystic kidney disease 2 (MIM#603860). Missense variants have been shown to impair wildtype protein localization (PMID: 28990932; PMID: 22117067). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 21868615). (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to threonine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (1 heterozygote, 0 homozygotes). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated zona pellucida domain (NCBI, PDB). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 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) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |