Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001050734 | SCV001214855 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2022-07-29 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 847231). 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 disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 affected with POLD1-related conditions. This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 691 of the POLD1 protein (p.Leu691Val). This variant is not present in population databases (gnomAD no frequency). |
| Ambry Genetics | RCV002416383 | SCV002729776 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-10 | criteria provided, single submitter | clinical testing | The p.L691V variant (also known as c.2071C>G), located in coding exon 16 of the POLD1 gene, results from a C to G substitution at nucleotide position 2071. The leucine at codon 691 is replaced by valine, an amino acid with highly 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. |