Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000645855 | SCV000767610 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2022-07-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 744 of the POLD1 protein (p.Gly744Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 537102). 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: "Probably Damaging"; 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 | RCV002424479 | SCV002730921 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-16 | criteria provided, single submitter | clinical testing | The p.G744D variant (also known as c.2231G>A), located in coding exon 17 of the POLD1 gene, results from a G to A substitution at nucleotide position 2231. The glycine at codon 744 is replaced by aspartic acid, 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. |
Gene |
RCV003320717 | SCV004025654 | uncertain significance | not provided | 2023-08-21 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Prevention |
RCV003953158 | SCV004779486 | uncertain significance | POLD1-related condition | 2024-02-21 | criteria provided, single submitter | clinical testing | The POLD1 c.2231G>A variant is predicted to result in the amino acid substitution p.Gly744Asp. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |