Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001071596 | SCV001236906 | uncertain significance | Parathyroid carcinoma | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 379 of the CDC73 protein (p.Asp379Asn). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with benign parathyroid lesion and/or hyperparathyroidism-jaw tumor syndrome (PMID: 16487440, 32590342). ClinVar contains an entry for this variant (Variation ID: 864409). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 | RCV002320358 | SCV002607032 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-28 | criteria provided, single submitter | clinical testing | The p.D379N variant (also known as c.1135G>A), located in coding exon 13 of the CDC73 gene, results from a G to A substitution at nucleotide position 1135. The aspartic acid at codon 379 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been identified in an individual with hyperparathyroidism-jaw tumor syndrome (Bradley KJ et al. Clin Endocrinol (Oxf) 2006 Mar;64(3):299-306). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003462623 | SCV004215578 | uncertain significance | Hyperparathyroidism 1 | 2023-08-26 | criteria provided, single submitter | clinical testing |