Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000684882 | SCV000812343 | uncertain significance | Parathyroid carcinoma | 2024-12-03 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 128 of the CDC73 protein (p.Ala128Thr). This variant is present in population databases (rs756584058, gnomAD 0.0009%). 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: 565343). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CDC73 protein function with a negative predictive value of 80%. 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 | RCV002352106 | SCV002619826 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-15 | criteria provided, single submitter | clinical testing | The p.A128T variant (also known as c.382G>A), located in coding exon 5 of the CDC73 gene, results from a G to A substitution at nucleotide position 382. The alanine at codon 128 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |