Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002048740 | SCV002310963 | uncertain significance | Parathyroid carcinoma | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 441 of the CDC73 protein (p.Arg441His). This variant is present in population databases (rs778432682, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CDC73-related conditions. ClinVar contains an entry for this variant (Variation ID: 1522712). 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 expected to disrupt CDC73 protein function. 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. |
| Ambry Genetics | RCV004044786 | SCV005028761 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-29 | criteria provided, single submitter | clinical testing | The p.R441H variant (also known as c.1322G>A), located in coding exon 15 of the CDC73 gene, results from a G to A substitution at nucleotide position 1322. The arginine at codon 441 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |