Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001011176 | SCV001171467 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-05 | criteria provided, single submitter | clinical testing | The p.R454S variant (also known as c.1360C>A), located in coding exon 10 of the POLD1 gene, results from a C to A substitution at nucleotide position 1360. The arginine at codon 454 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
| Invitae | RCV001365088 | SCV001561323 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2021-08-31 | 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 (ExAC no frequency). This sequence change replaces arginine with serine at codon 454 of the POLD1 protein (p.Arg454Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. ClinVar contains an entry for this variant (Variation ID: 819005). 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. 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"). |