Gene

TSC1

TSC complex subunit 1

Explore in graph →CI-GENE-00037230HGNC:12362 ENSG00000165699 NCBI 7248 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (9)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–9 of 9 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
KRAS G12D + TSC1 Loss-of-functionKRAS TSC11
Sirolimus	Lung Adenocarcinoma	Predictive	D	Supports Sensitivity Response

Cohorts

Alteration frequency by cohort (136)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved136 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Colorectal Cancer (MSK, Cancer Discovery 2022) coadread_mskresistance_2022	Colorectal Adenocarcinoma	Ssm

Literature

Linked publications (4)

25 per page, newest first.

pubmedPublishedShowing 1–4 of 4 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Genome sequencing identifies a basis for everolimus sensitivity.
· Science · 2012 · PMID 22923433 · validated civic_curation pubmed
Ultra deep sequencing detects a low rate of mosaic mutations in tuberous sclerosis complex.
· Hum Genet · 2010 · PMID 20165957 · validated civic_curation pubmed
TSC1 loss synergizes with KRAS activation in lung cancer development in the mouse and confers rapamycin sensitivity.
· Oncogene · 2010 · PMID 19966866 · validated civic_curation pubmed
Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with Tuberous Sclerosis Complex.
· Hum Mutat · 2011 · PMID 21309039 · validated civic_curation pubmed

TSC1 Frameshift Truncation1
Everolimus	Invasive Bladder Urothelial CarcinomaALIAS	Predictive	C	Supports Sensitivity Response	3	accepted	EID320 A patient with metastatic bladder cancer that responded well to the mTOR inhibitor everolimus was shown to harbor a TSC1 frameshift truncation mutation (c.1907_1908del, p.Glu636fs) and a nonsense NF2 … (full text at CIViC) PMID 22923433 · Iyer et al., 2012 · Open in CIViC	civic

TSC1 Frameshift Truncation1

Everolimus

Invasive Bladder Urothelial CarcinomaALIAS

Predictive

Supports Sensitivity Response

accepted

EID320

A patient with metastatic bladder cancer that responded well to the mTOR inhibitor everolimus was shown to harbor a TSC1 frameshift truncation mutation (c.1907_1908del, p.Glu636fs) and a nonsense NF2 … (full text at CIViC)

PMID 22923433 · Iyer et al., 2012 · Open in CIViC

civic

TSC1 Loss-of-function4
Everolimus	Tuberous SclerosisUNRESOLVED	Predictive	A	Supports Sensitivity Response	5	submitted	EID7280 In phase 3 trial patients with subependymal giant cell astrocytomas related to tuberous sclerosis complex (TSC) were randomly assigned to everolimus or placebo. Tumor response was observed 35% in ever… (full text at CIViC) PMID 23158522 · Franz et al., 2013 · Open in CIViC	civic
〃	Bladder Carcinoma	Predictive	B	Supports Sensitivity Response	3	accepted	EID155 Tumors (n=14) expressing TSC1 mutations (5/14) show notably more sensitivity to everolimus than their wild-type counterparts (9/14). A dramatic response was observed in a patient with combination of L… (full text at CIViC) PMID 22923433 · Iyer et al., 2012 · Open in CIViC	civic
MTOR Inhibitor	Renal Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	3	submitted	EID5837 In a retrospective study of 79 RCC patients treated with diverse rapalogs (mTOR inhibitors) inactivating TSC1 and TSC2-mutations and activating MTOR-mutations were significantly more common in respons… (full text at CIViC) PMID 26831717 · Kwiatkowski et al., 2016 · Open in CIViC	civic
〃	Renal Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Sensitivity Response	2	submitted	EID6053 In 5 patients with renal cell carcinoma who achieved durable disease control with mTOR inhibitors (median duration, 28 months), Custom target capture and ultradeep sequencing was used to identify alt… (full text at CIViC) PMID 24622468 · Voss et al., 2014 · Open in CIViC	civic

TSC1 Loss-of-function4

Everolimus

Tuberous SclerosisUNRESOLVED

Predictive

Supports Sensitivity Response

submitted

EID7280

In phase 3 trial patients with subependymal giant cell astrocytomas related to tuberous sclerosis complex (TSC) were randomly assigned to everolimus or placebo. Tumor response was observed 35% in ever… (full text at CIViC)

PMID 23158522 · Franz et al., 2013 · Open in CIViC

civic

〃

Bladder Carcinoma

Predictive

Supports Sensitivity Response

accepted

EID155

Tumors (n=14) expressing TSC1 mutations (5/14) show notably more sensitivity to everolimus than their wild-type counterparts (9/14). A dramatic response was observed in a patient with combination of L… (full text at CIViC)

PMID 22923433 · Iyer et al., 2012 · Open in CIViC

civic

MTOR Inhibitor

Renal Cell CarcinomaCURATED_BROADER

Predictive

Supports Sensitivity Response

submitted

EID5837

In a retrospective study of 79 RCC patients treated with diverse rapalogs (mTOR inhibitors) inactivating TSC1 and TSC2-mutations and activating MTOR-mutations were significantly more common in respons… (full text at CIViC)

PMID 26831717 · Kwiatkowski et al., 2016 · Open in CIViC

civic

〃

Renal Cell CarcinomaCURATED_BROADER

Predictive

Supports Sensitivity Response

submitted

EID6053

In 5 patients with renal cell carcinoma who achieved durable disease control with mTOR inhibitors (median duration, 28 months), Custom target capture and ultradeep sequencing was used to identify alt… (full text at CIViC)

PMID 24622468 · Voss et al., 2014 · Open in CIViC

civic

TSC1 mutation + TSC2 mutationTSC1 TSC21
Everolimus	Tuberous SclerosisUNRESOLVED	Predictive	A	Supports Sensitivity Response	4	submitted	EID11269 In this double-blind, placebo-controlled, phase 3 trial, 117 patients with tuberous sclerosis complex (TSC) and at least one lesion with a diameter of 1 cm or greater, and either serial growth of a su… (full text at CIViC) PMID 23158522 · Franz et al., 2013 · Open in CIViC	civic

TSC1 mutation + TSC2 mutationTSC1 TSC21

Everolimus

Tuberous SclerosisUNRESOLVED

Predictive

Supports Sensitivity Response

submitted

EID11269

In this double-blind, placebo-controlled, phase 3 trial, 117 patients with tuberous sclerosis complex (TSC) and at least one lesion with a diameter of 1 cm or greater, and either serial growth of a su… (full text at CIViC)

PMID 23158522 · Franz et al., 2013 · Open in CIViC

civic

TSC1 R1062W2
(predisposing)	Tuberous SclerosisUNRESOLVED	Predisposing	C	Supports Uncertain Significance	2	accepted	EID1768 Deep sequencing of TSC1 and TSC2 was performed on blood from a group of 38 sporadic Tuberous Sclerosis patients who had been previously studied with no mutation identified in TSC1 or TSC2. Five patien… (full text at CIViC) PMID 20165957 · Qin et al., 2010 · Open in CIViC	civic
〃	Tuberous SclerosisUNRESOLVED	Predisposing	D	Supports Uncertain Significance	3	accepted	EID1921 The authors used a transfection based immunoblot assay to assess the impact of TSC1 (and TSC2) variants. Numerous variants were tested independently across 4 replicates and the mean and s.e.m. were pl… (full text at CIViC) PMID 21309039 · Hoogeveen-Westerveld et al., 2011 · Open in CIViC	civic

TSC1 R1062W2

(predisposing)

Tuberous SclerosisUNRESOLVED

Predisposing

Supports Uncertain Significance

accepted

EID1768

Deep sequencing of TSC1 and TSC2 was performed on blood from a group of 38 sporadic Tuberous Sclerosis patients who had been previously studied with no mutation identified in TSC1 or TSC2. Five patien… (full text at CIViC)

PMID 20165957 · Qin et al., 2010 · Open in CIViC

civic

〃

Tuberous SclerosisUNRESOLVED

Predisposing

Supports Uncertain Significance

accepted

EID1921

The authors used a transfection based immunoblot assay to assess the impact of TSC1 (and TSC2) variants. Numerous variants were tested independently across 4 replicates and the mean and s.e.m. were pl… (full text at CIViC)

PMID 21309039 · Hoogeveen-Westerveld et al., 2011 · Open in CIViC

civic