Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000645794 | SCV000767549 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2022-12-14 | 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. 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 POLD1 protein function. ClinVar contains an entry for this variant (Variation ID: 537053). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. This variant is present in population databases (rs754416243, gnomAD 0.03%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 963 of the POLD1 protein (p.Ala963Val). |
| Ambry Genetics | RCV002440318 | SCV002749620 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-27 | criteria provided, single submitter | clinical testing | The p.A963V variant (also known as c.2888C>T), located in coding exon 22 of the POLD1 gene, results from a C to T substitution at nucleotide position 2888. The alanine at codon 963 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. 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. |