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Gene TSC1
Variant L180P
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions TSC1 L180P does not lie within any known functional domains of the Tsc1 protein (UniProt.org). L180P confers a loss of function on the Tsc1 protein as indicated by decreased Tsc1 protein expression and loss of mTOR pathway inhibition in cell culture (PMID: 18830229).
Associated Drug Resistance
Category Variants Paths

TSC1 mutant TSC1 inact mut TSC1 L180P

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Transcript NM_000368.5
gDNA chr9:g.132921943A>G
cDNA c.539T>C
Protein p.L180P
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_017015097 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
XM_017015097.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406606.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406596.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406598.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001162426.2 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406603.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406597.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
XM_005272211 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_000368.5 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406602.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
XM_017015096 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
XM_005272211.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_000368 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
XM_017015096.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
XM_017015098 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406592.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406594.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
XM_006717271 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406595.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406609.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406601.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406599.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406607.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
XM_011518979 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001162426.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406600.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
XM_006717271.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
XM_017015098.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001162426 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
XM_011518979.3 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
XM_011518979.2 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_000368.4 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406604.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406605.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406593.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38
NM_001406608.1 chr9:g.132921943A>G c.539T>C p.L180P RefSeq GRCh38/hg38

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  • 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

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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
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 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 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 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 mutant renal cell carcinoma conflicting Everolimus Clinical Study - Cohort Actionable In a retrospective analysis, TSC1, TSC2, or MTOR mutation status was not associated with progression-free survival in renal cell carcinoma patients treated with Afinitor (everolimus) (PMID: 30327302). 30327302
TSC1 mutant renal cell carcinoma conflicting Everolimus Case Reports/Case Series Actionable In a clinical study, treatment with Afinitor (everolimus) or Torisel (temsirolimus) resulted in more partial responses (odds ratio = 0.08, p=0.030) in patients with renal cell carcinoma harboring mTOR pathway mutations, including MTOR (n=8), TSC1 (n=1), and TSC2 (n=2), than those without mutations (n=76) (PMID: 31335987). 31335987
TSC1 mutant subependymal giant cell astrocytoma predicted - sensitive Everolimus Phase III Actionable In a Phase III trial (EXIST-1), Afinitor (everolimus) treatment resulted in a 50% or more tumor reduction in 35% (27/78) of adult and pediatric patients diagnosed with tuberous sclerosis complex and had subependymal giant cell astrocytoma, compared to 0% (0/39) in the placebo group, 85% (99/117) of the patients harbored mutations in TSC1 and/or TSC2 (PMID: 23158522; NCT00789828). 23158522
TSC1 mutant renal cell carcinoma predicted - sensitive Temsirolimus Case Reports/Case Series Actionable In a clinical study, treatment with Afinitor (everolimus) or Torisel (temsirolimus) resulted in more partial responses (odds ratio = 0.08, p=0.030) in patients with renal cell carcinoma harboring mTOR pathway mutations, including MTOR (n=8), TSC1 (n=1), and TSC2 (n=2), than those without mutations (n=76) (PMID: 31335987). 31335987
TSC1 mutant bladder carcinoma sensitive Everolimus Phase II Actionable A retrospective study of a Phase II trial correlated increased sensitivity to the mTOR inhibitor Afinitor (everolimus) with TSC1 mutations in bladder cancer patients (PMID: 22923433). 22923433
TSC1 mutant hepatocellular carcinoma decreased response Sorafenib Clinical Study - Cohort Actionable In a clinical case study, Nexavar (sorafenib) treatment of patients with hepatocellular carcinoma harboring Mtor pathway mutations in PIK3CA, PTEN, TSC2, or TSC1 (n=12), resulted in a lower disease control rate (8.3% vs. 40.2%), shorter progression-free survival (1.9 months vs. 5.3 months) and shorter overall survival (10.4 months vs. 17.9 months) compared to patients without mutations in this pathway (n=67) (PMID: 30373752; NCT01775072). 30373752
TSC1 mutant lung non-small cell carcinoma no benefit Vistusertib Case Reports/Case Series Actionable In a Phase II trial (NLMT), Vistusertib (AZD2014) treatment did not result in a confirmed response (0/5) or durable clinical benefit (0/5) in patients with non-small cell lung cancer harboring TSC1 or TSC2 mutations, thus the cohort was closed due to futility (PMID: 32669708, NCT02664935). 32669708