Confirmed germline pathogenic / likely-pathogenic variant in the RET proto-oncogene — MEN...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-MEN2-CONFIRMED-CARRIER`
Type	Red flag
Status	reviewed 2026-05-18 \| pending_clinical_signoff
Diseases	`DIS-MTC` `DIS-PHEOCHROMOCYTOMA`
Sources	`SRC-ATA-THYROID-2015` `SRC-NCCN-BCELL-2025` `SRC-NCCN-THYROID-2025`

Red Flag Origin

Definition	Confirmed germline pathogenic / likely-pathogenic variant in the RET proto-oncogene — MEN2A or MEN2B by mutation class. Patient has had germline RET testing returned positive; the pedigree-suspicion question is settled. No current personal cancer diagnosis in the carrier being assessed (current cancer diagnosis routes to treatment-track plan with RET-class status recorded). Mandates prophylactic thyroidectomy timed by RET class (HST e.g. M918T → infancy; high-risk e.g. C634 → age ≤5; moderate-risk → age 5-10) plus lifelong pheochromocytoma + parathyroid surveillance. Prevention-persona RedFlag (§20, v0.2-B confirmed-carrier surveillance pathway — distinct from RF-MEN2-FAMILY-HISTORY-SUSPICION which fires before testing).
Clinical direction	investigate
Category	other

Trigger Logic

{
  "any_of": [
    {
      "finding": "germline_ret_pathogenic_variant_confirmed",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

v0.2-B confirmed-carrier surveillance pathway — MEN2. Fires on documented germline RET pathogenic variant positivity in an asymptomatic individual. Engine routes to PreventionPlan recommending: (a) IND-MEN2-CARRIER-SURVEILLANCE (standard) — ATA-class-driven prophylactic thyroidectomy timing + calcitonin q6mo + plasma / urine metanephrines q1y from age 8-16 (RET-class-dependent) + PTH/Ca q1y in MEN2A class. (b) IND-MEN2-CARRIER-INTENSIFIED (aggressive) — earlier thyroidectomy + bilateral adrenalectomy discussion if bilateral pheochromocytoma emerges + cortical-sparing surgery option to preserve glucocorticoid function. STUB pending two-Clinical-Co-Lead signoff per CHARTER §6.1 dev-mode exemption. Lifetime tumor risk in confirmed RET carriers (Wells et al. ATA 2015): - MTC: near-100% penetrance; age of onset by RET class (MEN2B M918T infancy-toddlerhood; classic MEN2A C634 childhood-adolescence; moderate-risk RET adulthood) - Pheochromocytoma: ~50% in MEN2A and MEN2B; preferentially bilateral / adrenal medullary; emerges after MTC (age 30s-40s) - Primary hyperparathyroidism: ~20-30% in MEN2A only (absent in MEN2B); multi-glandular hyperplasia - Mucosal neuromas + marfanoid + corneal...

Used By

Algorithms

ALGO-MEN2-CARRIER-PROPHYLACTIC-THYROIDECTOMY-TIMING - ALGO-MEN2-CARRIER-PROPHYLACTIC-THYROIDECTOMY-TIMING

Indications

IND-MEN2-CARRIER-INTENSIFIED - IND-MEN2-CARRIER-INTENSIFIED
IND-MEN2-CARRIER-SURVEILLANCE - IND-MEN2-CARRIER-SURVEILLANCE

Red flag

RF-MEN2-FAMILY-HISTORY-SUSPICION - Family pedigree suggestive of Multiple Endocrine Neoplasia type 2 (MEN2A or MEN2B, RET-dr...