Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000610865 | SCV000712644 | uncertain significance | not specified | 2016-11-23 | criteria provided, single submitter | clinical testing | The p.Val290Met variant in POLD1 has not been previously reported in individuals with colorectal cancer but has been identified in 1/4142 of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSN P rs748657880). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Val290Met variant is uncertain. |
Invitae | RCV000645823 | SCV000767578 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2022-09-16 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 290 of the POLD1 protein (p.Val290Met). This variant is present in population databases (rs748657880, gnomAD 0.009%). 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: 505437). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POLD1 protein function. 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 |
RCV001568631 | SCV001792537 | uncertain significance | not provided | 2019-11-26 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect Has not been previously published as pathogenic or benign to our knowledge Observed in 0.0025% (5/201364) alleles in large population cohorts (Lek 2016) |