RET C634R is the most common MEN2A germline variant. In advanced / metastatic MEN2A-drive...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-RET-C634R-MTC |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-MTC |
| Sources | SRC-CIVIC SRC-NCCN-CNS-2025 |
Actionability Facts
| Biomarker | BIO-RET |
|---|---|
| Variant | C634R (germline — MEN2A) |
| Disease | DIS-MTC |
| ESCAT tier | IB |
| Recommended combinations | selpercatinib monotherapy, pralsetinib monotherapy |
| Contraindicated monotherapy | cabozantinib / vandetanib (selective-TKI preferred in selective-TKI era) |
| Evidence summary | RET C634R is the most common MEN2A germline variant. In advanced / metastatic MEN2A-driven MTC, selpercatinib and pralsetinib have activity comparable to M918T disease (LIBRETTO-001 RET-mutant MTC cohort). FDA labels for selpercatinib/pralsetinib in RET-mutant MTC encompass germline / extracellular-domain variants. C634R also drives prophylactic-thyroidectomy timing in MEN2A kindred. |
Notes
ESCAT IB (slightly lower than M918T because LIBRETTO-531 1L superiority data are most robust in M918T-enriched cohorts; C634 is treated identically by FDA label and clinical practice). OncoKB Level 1. Mandatory pheochromocytoma + hyperparathyroidism screening (MEN2A syndrome). Source-gap: SRC-NCCN-THYROID-2025 placeholder; SRC-LIBRETTO001-DRILON-2020 not yet ingested.
Used By
No reverse references found in the YAML corpus.