RET codon-based MEN2 classification (MEN2A / MEN2B / FMTC)

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

ID	`BIO-RET-MEN2-CLASSIFICATION`
Type	Biomarker
Aliases	ATA RET risk-level stratificationFMTC vs MEN2AMEN2A vs MEN2BRET MEN2 subtype classificationКласифікація MEN2 за кодоном RET (MEN2A / MEN2B / FMTC)
Status	reviewed 2026-05-18 \| pending_clinical_signoff
Diseases	None declared
Sources	`SRC-ENDOCRINE-SOCIETY-MEN-2023` `SRC-NCCN-THYROID-2025`

Biomarker Facts

Biomarker type	composite_score
Mutation details	{"functional_impact": "activating (constitutive kinase signaling)", "gene": "RET", "gene_hugo_id": "HGNC:9967", "variant_type": "missense (specific codon assignment predicts phenotype)"}
Related biomarkers	`BIO-RET-GERMLINE` `BIO-RET-M918T`

Notes

Composite codon-phenotype classification for MEN2 (germline RET- activating pathogenic variants). ATA 2015 / NCCN 2025 stratify carriers into three syndromic subtypes and four codon-based risk tiers driving prophylactic-thyroidectomy timing. Syndromic subtypes: • MEN2A (~75% of MEN2): MTC + pheochromocytoma (~50%) + primary hyperparathyroidism (~25%); occasional cutaneous lichen amyloidosis or Hirschsprung disease. Codons mostly cysteine-rich extracellular domain (609, 611, 618, 620, 630, 634). • MEN2B (~5%): MTC (earliest onset, most aggressive) + pheo (~50%) + marfanoid habitus + mucosal neuromas (tongue, lips, GI) + medullated corneal nerves. Codon M918T (95%) or A883F (rare). • FMTC (~20%): MTC only, no pheo / no HPT. Codons 768, 790, 791, 804, 891 (lower-risk codons) — increasingly considered MEN2A variant with low-penetrance pheo. ATA RET risk tiers driving prophylactic-thyroidectomy timing: • Highest risk (ATA HST): M918T → thyroidectomy by age 1 (before metastatic MTC). • High risk (ATA H): C634, A883F → by age 5. • Moderate risk (ATA MOD): 609, 611, 618, 620, 630, 768, 790, 791, 804, 891 → individualized; consider 5-10 years (basal calcitonin + neck US trigger). Surveilla...

Used By

No reverse references found in the YAML corpus.