Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001051999 | SCV001216184 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2019-04-14 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with POLD1-related conditions. 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 229 of the POLD1 protein (p.Gln229His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. |
Prevention |
RCV003393814 | SCV004118745 | uncertain significance | POLD1-related condition | 2022-08-24 | criteria provided, single submitter | clinical testing | The POLD1 c.687G>C variant is predicted to result in the amino acid substitution p.Gln229His. 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. In ClinVar this variant has been interpreted as uncertain (https://ncbi.nlm.nih.gov/clinvar/variation/848278/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Gene |
RCV003442175 | SCV004170259 | uncertain significance | not provided | 2023-04-03 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31034466) |