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Gene TSC1
Variant inact mut
Impact List unknown
Protein Effect loss of function
Gene Variant Descriptions TSC1 inact mut indicates that this variant results in a loss of function of the Tsc1 protein. However, the specific amino acid change has not been identified.
Associated Drug Resistance
Category Variants Paths

TSC1 mutant TSC1 inact mut

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No Variant Reference Transcript is Available.
No transcript is Available.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
TSC1 inact mut renal cell carcinoma predicted - sensitive Everolimus Clinical Study - Cohort Actionable In a retrospective analysis, 28% (12/43) of metastatic renal cell carcinoma patients who responded to rapalogs, Afinitor (everolimus) or Torisel (temsirolimus), harbored inactivating TSC1, TSC2 mutations and/or activating MTOR mutations, compared to 11% (4/36) in patients who did not respond to therapy (PMID: 26831717). 26831717
TSC1 inact mut Advanced Solid Tumor no benefit Everolimus Phase II Actionable In a Phase II trial, Afinitor (everolimus) treatment resulted in limited activity with an objective response rate of 7% (2/30, 2 partial responses), stable disease in an additional 40% (12/30), a clinical benefit rate of 13% (4/30), a median progression-free survival of 2.3 months, and a median overall survival of 7.3 months in patients with advanced solid tumors harboring inactivating TSC1 or TSC2 mutations or activating MTOR mutations (PMID: 33727259; NCT02201212). 33727259
TSC1 inact mut renal cell carcinoma predicted - sensitive Temsirolimus Clinical Study - Cohort Actionable In a retrospective analysis, 28% (12/43) of metastatic renal cell carcinoma patients who responded to rapalogs, Afinitor (everolimus) or Torisel (temsirolimus), harbored inactivating TSC1, TSC2 mutations and/or activating MTOR mutations, compared to 11% (4/36) in patients who did not respond to therapy (PMID: 26831717). 26831717
TSC1 inact mut transitional cell carcinoma no benefit Sapanisertib Phase II Actionable In a Phase II trial, treatment with Sapanisertib (MLN0128) in metastatic urothelial carcinoma patients with either a TSC1 or TSC2 activating mutation (n=13) did not result in an objective response and led to a median overall survival of 3.4 months, and the trial was terminated early due to limited clinical activity and poor drug tolerability (Journal of Clinical Oncology 39, no. 6_suppl (February 20, 2021) 431-431; NCT03047213). detail...
TSC1 inact mut islet cell tumor not applicable N/A Guideline Risk Factor Germline inactivating mutations in TSC1 result in tuberous sclerosis complex (TSC), which is associated with increased risk of developing pancreatic neuroendocrine tumors (NCCN.org). detail...
TSC1 inact mut clear cell renal cell carcinoma not applicable N/A Guideline Risk Factor Germline inactivating mutations in TSC1 result in tuberous sclerosis complex (TSC), which is associated with increased risk of developing clear cell renal cell carcinoma (NCCN.org). detail...
TSC1 inact mut perivascular epithelioid cell tumor predicted - sensitive Nab-rapamycin Phase II Actionable In a Phase II trial (AMPECT), Fyarro (nab-rapamycin) treatment in patients with perivascular epithelioid cell tumors (PEComas) resulted in partial response in 20% (1/5) of patients with TSC1 mutations, 89% (8/9) of patients with TSC2 mutations, and 9% (1/11) of patients without a TSC1 or TSC2 mutation (PMID: 34637337; NCT02494570). 34637337
TSC1 inact mut Advanced Solid Tumor predicted - sensitive Nab-rapamycin Clinical Study Actionable In a clinical study, Fyarro (nab-rapamycin) treatment in patients with advanced solid tumors harboring mutations in TSC1 or TSC2 led to a partial response in 4 patients, stable disease in 2 patients, and progressive disease in 1 patient of 7 enrolled patients (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 3111-3111; NCT03817515). detail...
TSC1 inact mut castration-resistant prostate carcinoma predicted - sensitive CC-115 + Enzalutamide Phase I Actionable In a Phase Ib trial, Xtandi (enzalutamide) plus CC-115 was safe and led to a PSA reduction >= 50% (PSA50) in 80% (32/40) and >=90% (PSA90) in 58% (23/40) of metastatic castration-resistant prostate cancer patients at 12 weeks, and patients with PIK3CA activating mutations or PTEN or TSC1/2 loss of function (n=16) achieved a PSA50, PSA90, and median radiographic progression-free survival of 94%, 63%, and 19.6 mo vs 67%, 47%, and 22.1 mo in PI3K pathway wild-type patients (n=15) (PMID: 37980367; NCT02833883). 37980367