Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000473753 | SCV000547620 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-08-10 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 408068). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with POLD1-related conditions. This variant is present in population databases (rs553279670, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 155 of the POLD1 protein (p.Gly155Ala). 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. |
Gene |
RCV001568519 | SCV001792403 | uncertain significance | not provided | 2021-06-29 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 27535533) |
Center for Genomic Medicine, |
RCV002268076 | SCV002551876 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002339152 | SCV002640296 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-09 | criteria provided, single submitter | clinical testing | The p.G155A variant (also known as c.464G>C) is located in coding exon 4 of the POLD1 gene. The glycine at codon 155 is replaced by alanine, an amino acid with similar properties. This change occurs in the first base pair of coding exon 4. 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. |