Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000645968 | SCV000767723 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2019-11-23 | criteria provided, single submitter | clinical testing | This variant is an out-of-frame deletion of the genomic region encompassing exons 4-10 of the POLD1 gene. This is expected to create a premature translational stop signal and result in an absent or disrupted protein product. Deletion of exons 4-10 has not been reported in the literature in individuals with POLD1-related disease. Missense variants that disrupt the 3'-5' exonuclease (proof-reading) activity of the POLD1 protein, while not abolishing its polymerase enzyme activity, are associated with an increased risk for colonic adenomatous polyps and colon cancer (PMID: 23263490, 23447401). Loss-of-function truncating variants, which result in an absent or severely disrupted POLD1 protein, are therefore unlikely to be associated with disease. Without further clinical and genetic evidence, however, this variant has been classified as a Variant of Uncertain Significance. |