Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000645869 | SCV000767624 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2017-08-06 | criteria provided, single submitter | clinical testing | 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with POLD1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with proline at codon 382 of the POLD1 protein (p.Ser382Pro). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and proline. |
| Ambry Genetics | RCV003162929 | SCV003857576 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-17 | criteria provided, single submitter | clinical testing | The p.S382P variant (also known as c.1144T>C), located in coding exon 9 of the POLD1 gene, results from a T to C substitution at nucleotide position 1144. The serine at codon 382 is replaced by proline, 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. |