TSC1 loss-of-function mutation (hamartin)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-TSC1 |
|---|---|
| Type | Biomarker |
| Aliases | TSC1 mutationМутація втрати функції TSC1 (гамартин) |
| Status | reviewed 2026-05-04 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-MILES-MCCORMACK-2011 SRC-NCCN-KIDNEY-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"exon": "multiple", "functional_impact": "loss-of-function", "gene": "TSC1", "variant_type": "loss-of-function (frameshift, nonsense, splice, large deletion)"} |
| Measurement | MethodGermline NGS panel (blood/saliva) for TSC diagnosis; tumor NGS for somatic TSC1/TSC2 in LAM/renal AML. TSC1 mutations less common than TSC2 in sporadic LAM (~10% vs ~80%). |
| Actionability lookup | {"gene": "TSC1", "variant": "loss_of_function"} |
| Related biomarkers | None declared |
Notes
TSC1 (hamartin) forms a heterodimeric complex with TSC2 (tuberin) that acts as a GTPase activating protein (GAP) for Rheb, maintaining mTORC1 in an inactive state. Loss of either TSC1 or TSC2 → constitutive mTORC1 activation → protein synthesis, cell growth, proliferation. Clinical manifestations of TSC1 loss: (1) Tuberous Sclerosis Complex (TSC) — germline TSC1 (~30%) or TSC2 (~70%): cortical tubers, SEGA, renal AML, cardiac rhabdomyomas, LAM (females), skin lesions. TSC1 germline associated with milder phenotype than TSC2. (2) LAM — predominantly somatic TSC2 (>80%) or rarely TSC1 in sporadic LAM. TSC-associated LAM has germline TSC mutation. (3) Renal angiomyolipoma (sporadic) — somatic TSC1/TSC2 in ~50%. mTOR inhibitors (everolimus, sirolimus) are approved for multiple TSC/LAM manifestations: - Sirolimus: LAM (MILES 2011; FDA 2015) - Everolimus: SEGA (EXIST-1), renal AML (EXIST-2), TSC-related seizures (EXIST-3); renal cell carcinoma (SRC-BOLERO2 — different indication via PIK3/AKT/mTOR pathway). Note: the BIO entity covers TSC1 specifically; TSC2 mutations are clinically similar but a separate gene — both treated with mTOR inhibitors.
Used By
Actionability
BMA-TSC1-LAM- Sirolimus (rapamycin), an mTORC1 inhibitor, is FDA-approved (May 2015) and EMA-approved (...BMA-TSC1-TSC-RENAL-AML- Everolimus (mTOR inhibitor) is FDA-approved (2012) for renal angiomyolipoma (AML) associa...
Diseases
DIS-LAM- Lymphangioleiomyomatosis (LAM)
Indications
IND-LAM-1L-SIROLIMUS- IND-LAM-1L-SIROLIMUS