Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000506025 | SCV000601870 | uncertain significance | not specified | 2017-07-05 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002527342 | SCV003315201 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln399*) in the POLD1 gene. Missense variants that disrupt the 3'-5' exonuclease (proof-reading) activity of the POLD1 protein are associated with an increased risk for colonic adenomatous polyps and colon cancer (PMID: 23263490, 23447401). However, loss-of-function variants that result in an absent or severely disrupted POLD1 protein, and missense variants outside the exonuclease domain, are unlikely to be associated with polyposis or colon cancer. 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: 439248). 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. |