Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002320832 | SCV002608526 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-05 | criteria provided, single submitter | clinical testing | The p.A377V variant (also known as c.1130C>T), located in coding exon 13 of the CDC73 gene, results from a C to T substitution at nucleotide position 1130. The alanine at codon 377 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. 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. |
Labcorp Genetics |
RCV003607446 | SCV004475737 | uncertain significance | Parathyroid carcinoma | 2023-05-07 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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. 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 not expected to disrupt CDC73 protein function. ClinVar contains an entry for this variant (Variation ID: 1728200). This variant has not been reported in the literature in individuals affected with CDC73-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 377 of the CDC73 protein (p.Ala377Val). |