Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000609517 | SCV000731496 | uncertain significance | not specified | 2017-04-05 | criteria provided, single submitter | clinical testing | The p.Arg1008His variant in POLD1 has not been previously reported in individual s with colorectal cancer. Data from large population studies is insufficient to assess the frequency of this variant. Computational prediction tools and conserv ation analysis do not provide strong support for or against an impact to the pro tein. In summary, the clinical significance of the p.Arg1008His variant is uncer tain. |
| Invitae | RCV000645838 | SCV000767593 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-08-27 | criteria provided, single submitter | clinical testing | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POLD1 protein function. ClinVar contains an entry for this variant (Variation ID: 517284). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1008 of the POLD1 protein (p.Arg1008His). |