POLE germline pathogenic variant (proofreading domain)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-POLE-GERMLINE |
|---|---|
| Type | Biomarker |
| Aliases | POLE germline pathogenic variantPOLE germline патогенний варіант (proofreading-домен) |
| Status | reviewed 2026-05-18 | pending_clinical_signoff |
| Diseases | DIS-CRC |
| Sources | SRC-NCCN-GENETIC-FAMILIAL-CRC-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"functional_impact": "loss_of_function", "gene": "POLE", "gene_hugo_id": "HGNC:9177", "variant_type": "missense_or_truncating"} |
| Related biomarkers | BIO-POLE-HYPERMUTATOR |
Notes
POLE germline (exonuclease / proofreading-domain variants) — drives Polymerase-Proofreading-Associated Polyposis (PPAP). Autosomal dominant; oligopolyposis (often <100 adenomas) + early-onset CRC + endometrial cancer; reported brain tumors. Tumors are typically ultramutated (TMB > 100 mut/Mb) and may respond to immune-checkpoint inhibitors. Surveillance: colonoscopy q1-2y from late teens; consider endometrial surveillance. STUB pending two-Co-Lead signoff.
Used By
Actionability
BMA-POLE-GERMLINE-POLYMERASE-PROOFREADING- POLE germline pathogenic variants in the exonuclease (proofreading) domain cause polymera...