Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000545910 | SCV000646475 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2022-06-08 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 454 of the POLD1 protein (p.Arg454Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 469191). 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759930 | SCV000889643 | uncertain significance | not provided | 2018-06-05 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002384179 | SCV002699995 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-02 | criteria provided, single submitter | clinical testing | The p.R454C variant (also known as c.1360C>T), located in coding exon 10 of the POLD1 gene, results from a C to T substitution at nucleotide position 1360. The arginine at codon 454 is replaced by cysteine, an amino acid with highly 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. |