Variant · Snv

KRAS G12C

CI-VAR-00001604Explore in graph →NP_004976.2:p.Gly12CysNM_004985.4:c.34G>TClinVar 12578 CIViC 78 rs121913530

Curated evidence

Evidence by cancer (65 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–50 of 65 evidence items across 6 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Lung Adenocarcinoma1
KRAS G12C	Crizotinib	Predictive	C	Supports Resistance	—	submitted	EID3983 In two lung adenocarcinoma patients with EML4-ALK rearrangement (known to be sensitizing to crizotinib) and KRAS G12C co-mutation, progressive disease in response to 2nd-line crizotinib monotherapy wa… (full text at CIViC) PMID 26712101 · Ulivi et al., 2016 · Open in CIViC	civic
Lung Non-Small Cell Carcinoma22
KRAS G12C	(prognostic)	Prognostic	B	Supports Poor Outcome	3	accepted	EID1217 In a study of 48 NSCLC patients, those with G12C or G12V mutant KRAS were associated with decreased progression free survival (1.84 months) compared with other KRAS mutants or with wild-type KRAS (3.3… (full text at CIViC) PMID 22247021 ·

ClinVar

Clinical significance (1)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
12578	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2	Lung carcinoma; Non-small cell lung carcinoma; Endometrial carcinoma; Lung adenocarcinoma; Gallbladder cancer; RASopathy; Lung cancer; Neoplasm; Adenocarcinoma of the large intestine; Embryonal rhabdomyosarcoma; Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype; Ovarian mucinous adenocarcinoma; Noonan syndrome	germline/somatic

Malignant Colorectal Neoplasm23
KRAS G12C	Adagrasib + CetuximabCombination	Predictive	A	Supports Sensitivity Response	4	accepted	EID12063 The efficacy of adagrasib + cetuximab combination therapy was tested in 94 patients harbouring colorectal cancers with KRAS G12C mutations. ORR was used as the primary end-point for the study. The ORR… (full text at CIViC) PMID 38587856 · Yaeger et al., 2024 · Open in CIViC	civic
KRAS G12C	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3962 In a retrospective study of 30 metastatic colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation (n=13) treated with cetuximab and standard chemotherapy were associated with an absen… (full text at CIViC) PMID 16618717 · Lièvre et al., 2006 · Open in CIViC	civic
KRAS G12C	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3963 In a retrospective study of 113 metastatic irinotecan-refractory colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation treated with cetuximab plus irinotecan (34/83) were associated… (full text at CIViC) PMID 17998284 · De Roock et al., 2008 · Open in CIViC	civic
KRAS G12C	Cetuximab	Predictive	C	Supports Resistance	—	rejected	EID3964 In a retrospective study of 168 metastatic colorectal cancer patients, patients with a KRAS exon 2 mutation (32/92) treated with cetuximab as salvage therapy (second-line therapy or higher) in combina… (full text at CIViC) PMID 19603024 · Souglakos et al., 2009 · Open in CIViC	civic
KRAS G12C	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3965 In a retrospective study of 59 metastatic, chemotherapy-refractory, colorectal cancer patients, patients with a KRAS exon 2 mutation (n=22) treated with cetuximab and standard chemotherapy were assoc… (full text at CIViC) PMID 17375050 · Di Fiore et al., 2007 · Open in CIViC	civic
KRAS G12C	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3966 In a retrospective study of 89 metastatic irinotecan-refractory colorectal cancer patients, patients with a KRAS codon 12 or 13 mutation (n=24) treated with cetuximab plus chemotherapy were associated… (full text at CIViC) PMID 18202412 · Lièvre et al., 2008 · Open in CIViC	civic
KRAS G12C	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3968 In a retrospective study of 572 advanced colorectal cancer patients, patients treated with cetuximab and best supportive care with a KRAS exon 2 mutation (81/164) were associated with reduced response… (full text at CIViC) PMID 18946061 · Karapetis et al., 2008 · Open in CIViC	civic
KRAS G12C	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3969 In a phase 3 clinical study of 1,198 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFIRI were associated with reduced overal… (full text at CIViC) PMID 21502544 · Van Cutsem et al., 2011 · Open in CIViC	civic
KRAS G12C	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3970 In a phase 2 clinical study of 344 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFOX-4 (n=52) were associated with reduced … (full text at CIViC) PMID 19114683 · Bokemeyer et al., 2009 · Open in CIViC	civic
KRAS G12C	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3971 In a retrospective study of 95 metastatic colorectal cancer patients, patients harboring KRAS activating mutation (n=33) and treated with cetuximab plus standard chemotherapy were reportedly non-respo… (full text at CIViC) PMID 20010090 · Yen et al., 2010 · Open in CIViC	civic
KRAS G12C	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3972 In a phase 3 clinical study (NCT00154102) of 1198 metastatic colorectal cancer patients, patients harboring KRAS codon 12 or 13 mutations and treated with cetuximab plus FOLFIRI (n=105) were associate… (full text at CIViC) PMID 19339720 · Van Cutsem et al., 2009 · Open in CIViC	civic
KRAS G12C	Cetuximab + ChemotherapyCombination	Predictive	B	Supports Resistance	3	accepted	EID3967 This was a retrospective study of 691 cetuximab treated patients with metastatic, chemotherapy refractory colorectal cancer. Of those, 16 patients harbored KRAS G12C, were BRAF, NRAS and PIK3CA wt, an… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
KRAS G12C	Dactolisib + SelumetinibCombination	Predictive	D	Supports Sensitivity Response	2	accepted	EID2212 In 28 out of 40 (70%) metastatic colorectal cancer tumors harboring BRAF, KRAS, NRAS or PIK3CA mutations and implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC	civic
KRAS G12C	Erlotinib + GefitinibSubstitutes	Predictive	B	Supports Resistance	3	accepted	EID1216 In a study of 448 metastatic colorectal cancer patients treated with EGFR-TKIs and tested for EGFR and KRAS mutations, 69 tested positive for KRAS mutations. In 38 EGFR wildtype patients treated with … (full text at CIViC) PMID 23313110 · Fiala et al., 2013 · Open in CIViC	civic
KRAS G12C	Palbociclib	Predictive	D	Supports Sensitivity Response	—	submitted	EID3975 In an in vitro study, SW837 cell line expressing KRAS G12C mutation were associated with sensitivity to palbociclib treatment as compared to cells treated with DMSO control. Sensitivity was determine… (full text at CIViC) PMID 27167191 · Lee et al., 2016 · Open in CIViC	civic
KRAS G12C	Panitumumab	Predictive	C	Supports Resistance	3	accepted	EID2253 In a retrospective study of 427 metastatic colorectal patients, KRAS mutations were observed in 43% of the tumor samples. Patients with mutations in codon 12 or 13 of KRAS were associated with reduced… (full text at CIViC) PMID 18316791 · Amado et al., 2008 · Open in CIViC	civic
KRAS G12C	Panitumumab	Predictive	C	Supports Resistance	—	submitted	EID2254 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 16953233 · Oliveira et al., 2007 · Open in CIViC	civic
KRAS G12C	Panitumumab	Predictive	C	Supports Resistance	—	submitted	EID2255 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 2547513 · Bos, 1989 · Open in CIViC	civic
KRAS G12C	Panitumumab	Predictive	C	Supports Resistance	—	submitted	EID2256 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 8462792 · Benhattar et al., 1993 · Open in CIViC	civic
KRAS G12C	Regorafenib Anhydrous	Predictive	D	Supports Resistance	2	accepted	EID3973 In an in vitro study, a human colon adenocarcinoma SW48 cell line expressing KRAS G12C mutation demonstrated resistance to regorafenib treatment (IC50: 386.22 nM vs. 114.28 nM, P<0.01) compared to SW4… (full text at CIViC) PMID 26161928 · Camaj et al., 2015 · Open in CIViC	civic
KRAS G12C	Cetuximab + SotorasibCombination	Predictive	D	Supports Sensitivity Response	3	submitted	EID13300 Seven KRAS G12C mutant colorectal cancer cell (CRC) lines and two KRAS G12C mutant non-small lung cancer (NSLC) lines were treated with the KRAS G12C inhibitor AMG510 (sotorasib). After 24 hours, all … (full text at CIViC) PMID 32430388 · Amodio et al., 2020 · Open in CIViC	civic
KRAS G12C	Panitumumab + SotorasibCombination	Predictive	A	Supports Sensitivity Response	4	accepted	EID12264 In this phase 3 trial, patients with chemorefractory metastatic colorectal cancer harbouring KRAS G12C mutations were assigned to one of three groups. The first group received 960 mg of sotorasib (KRA… (full text at CIViC) PMID 37870968 · Fakih et al., 2023 · Open in CIViC	civic
KRAS G12C	Sunitinib	Predictive	D	Supports Resistance	—	submitted	EID3974 In an in vitro study, colorectal cancer SW48 cell line expressing KRAS G12C mutation demonstrated reduced sensitivity to sunitinib treatment (IC50: 7.2uM vs. 2.6uM, P<0.05) compared to SW48 cells expr… (full text at CIViC) PMID 23455880 · Modest et al., 2013 · Open in CIViC	civic

Malignant Lung Neoplasm2
KRAS G12C	(diagnostic)	Diagnostic	B	Supports Positive	2	accepted	EID227 KRAS G12C occur more frequently in women than men. PMID 23014527 · Dogan et al., 2012 · Open in CIViC	civic
KRAS G12C	Gefitinib	Predictive	B	Supports Resistance	2	accepted	EID2257 In recurrent lung cancer patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib, patients with KRAS mutations had a lower frequency of partial response (PR) and… (full text at CIViC) PMID 17409929 · Endoh et al., 2006 · Open in CIViC	civic