Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000645827 | SCV000767582 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2022-02-23 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 537081). 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 glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 631 of the POLD1 protein (p.Gly631Ser). |
| Ambry Genetics | RCV002406415 | SCV002722506 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-19 | criteria provided, single submitter | clinical testing | The p.G631S variant (also known as c.1891G>A), located in coding exon 14 of the POLD1 gene, results from a G to A substitution at nucleotide position 1891. The glycine at codon 631 is replaced by serine, an amino acid with similar 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. |