Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000482915 | SCV000573357 | uncertain significance | not provided | 2017-02-24 | criteria provided, single submitter | clinical testing | The Y183C variant in the UMOD gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Y183C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Y183C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret Y183C as a variant of uncertain significance |
| Victorian Clinical Genetics Services, |
RCV002272254 | SCV002557490 | likely pathogenic | Familial juvenile hyperuricemic nephropathy type 1 | 2022-09-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0104 - Dominant negative is a known mechanism of disease in this gene and is associated with tubulointerstitial kidney disease (MIM#162000) (GeneReviews, PMID: 22117067). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Intra-familial variability has been reported (PMID: 21868615). (I) 0200 - Variant is predicted to result in a missense amino acid change from tyrosine to cysteine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. It has been reported in at least two families with autosomal dominant tubulointerstitial kidney disease (PMID: 34519781). (SP) 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 |
| Fulgent Genetics, |
RCV002272254 | SCV002793903 | uncertain significance | Familial juvenile hyperuricemic nephropathy type 1 | 2022-05-19 | criteria provided, single submitter | clinical testing |