Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV002251387 | SCV001273709 | likely benign | Familial juvenile hyperuricemic nephropathy type 1 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
| Labcorp Genetics |
RCV002556280 | SCV003023061 | uncertain significance | not provided | 2023-08-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 375 of the UMOD protein (p.Arg375Trp). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt UMOD protein function. ClinVar contains an entry for this variant (Variation ID: 884578). This variant has not been reported in the literature in individuals affected with UMOD-related conditions. This variant is present in population databases (rs373609971, gnomAD 0.005%). |
| Fulgent Genetics, |
RCV002251387 | SCV005638488 | uncertain significance | Familial juvenile hyperuricemic nephropathy type 1 | 2023-12-28 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004538338 | SCV004725317 | uncertain significance | UMOD-related disorder | 2024-01-12 | no assertion criteria provided | clinical testing | The UMOD c.1123C>T variant is predicted to result in the amino acid substitution p.Arg375Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0050% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |