Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001986920 | SCV002277695 | uncertain significance | Parathyroid carcinoma | 2020-11-26 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CDC73-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tryptophan with cysteine at codon 492 of the CDC73 protein (p.Trp492Cys). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and cysteine. |
| Ambry Genetics | RCV003303595 | SCV004003933 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-31 | criteria provided, single submitter | clinical testing | The p.W492C variant (also known as c.1476G>C), located in coding exon 16 of the CDC73 gene, results from a G to C substitution at nucleotide position 1476. The tryptophan at codon 492 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |