TSC1 germline pathogenic variants drive Tuberous Sclerosis Complex (TSC) — an mTOR-pathwa...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-TSC1-GERMLINE-TUBEROUS-SCLEROSIS |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-05-18 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-RCC |
| Sources | SRC-NCCN-CNS-2025 |
Actionability Facts
| Biomarker | BIO-TSC1-GERMLINE |
|---|---|
| Variant | TSC1 germline pathogenic (hamartin loss-of-function) |
| Disease | DIS-RCC |
| ESCAT tier | IIA |
| Recommended combinations | everolimus 10 mg PO daily — TSC-associated SEGA (not amenable to resection) or renal AML ≥3 cm, sirolimus — LAM (off-label TSC variant) with FEV1 decline, multidisciplinary surveillance per TSC Consensus Conference 2012/2021 |
| Evidence summary | TSC1 germline pathogenic variants drive Tuberous Sclerosis Complex (TSC) — an mTOR-pathway hyperactivation syndrome with multi-organ tumor predisposition: subependymal giant cell astrocytoma (SEGA), renal angiomyolipomas (AML), lymphangioleiomyomatosis (LAM, females), cardiac rhabdomyomas, and cortical tubers. Confirmed-carrier surveillance protocol (per Tuberous Sclerosis Complex Consensus Conference / NCCN CNS): brain MRI q1-3y through age 25 for SEGA, renal MRI/US q1-3y from diagnosis (lifelong) for AML, pulmonary function tests + HRCT chest q5-10y in adult females for LAM, baseline echocardiogram + ECG, dermatology and ophthalmology exam annually. mTOR inhibitors (everolimus, sirolimus) are active across SEGA, growing renal AMLs (≥3 cm), and LAM — these are surveillance-triggered interventions, not prophylactic. ESCAT IIA (predisposition with established surveillance + targeted therapy on progression). |
Notes
STUB — Wave A+B germline expansion. Linked Indication: none (no TSC-specific Indication entity exists yet; surveillance triggered via RF / Algorithm layer). Two-Clinical-Co-Lead signoff queued. mTOR inhibitor activity is well-established (EXIST-1/2/3 trials) — TSC1 and TSC2 are functionally equivalent for treatment indication; TSC2 carriers tend to have more severe phenotype but the same surveillance/treatment protocol applies.
Used By
No reverse references found in the YAML corpus.