Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001049759 | SCV001213828 | uncertain significance | Parathyroid carcinoma | 2019-11-17 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. 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 proline with leucine at codon 339 of the CDC73 protein (p.Pro339Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. |
| Ambry Genetics | RCV002339252 | SCV002641288 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-23 | criteria provided, single submitter | clinical testing | The p.P339L variant (also known as c.1016C>T), located in coding exon 11 of the CDC73 gene, results from a C to T substitution at nucleotide position 1016. The proline at codon 339 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |