Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000563151 | SCV000674311 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-07 | criteria provided, single submitter | clinical testing | The p.V462M variant (also known as c.1384G>A), located in coding exon 11 of the POLD1 gene, results from a G to A substitution at nucleotide position 1384. This variant impacts the first base pair of coding exon 11. The valine at codon 462 is replaced by methionine, an amino acid with highly similar properties. 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. |
| Invitae | RCV000801809 | SCV000941605 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-05-05 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with POLD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 462 of the POLD1 protein (p.Val462Met). ClinVar contains an entry for this variant (Variation ID: 486084). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. |