Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000686677 | SCV000814205 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2018-06-06 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with POLD1-related disease. This sequence change replaces arginine with leucine at codon 1086 of the POLD1 protein (p.Arg1086Leu). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). 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: "Benign"; 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 | RCV002325362 | SCV002611021 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-16 | criteria provided, single submitter | clinical testing | The p.R1086L variant (also known as c.3257G>T), located in coding exon 26 of the POLD1 gene, results from a G to T substitution at nucleotide position 3257. The arginine at codon 1086 is replaced by leucine, 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. |