Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000805692 | SCV000945658 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2022-12-26 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 650529). 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 glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1105 of the POLD1 protein (p.Glu1105Val). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV002325564 | SCV002606178 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-03 | criteria provided, single submitter | clinical testing | The p.E1105V variant (also known as c.3314A>T), located in coding exon 26 of the POLD1 gene, results from an A to T substitution at nucleotide position 3314. The glutamic acid at codon 1105 is replaced by valine, an amino acid with dissimilar 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. |