Variant · Snv

KRAS G12S

CI-VAR-00001618Explore in graph →NP_004976.2:p.Gly12SerNM_004985.4:c.34G>AClinVar 12584 CIViC 913 rs121913530

Curated evidence

Evidence by cancer (37 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 1–37 of 37 evidence items across 7 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 Non-Small Cell Carcinoma6
KRAS G12S	Erlotinib	Predictive	C	Supports Resistance	—	submitted	EID4013 In a retrospective study of 274 stage IIIB or IV non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (25/55) treated with erlotinib plus chemotherapy were associated with decreas… (full text at CIViC) PMID 16043828 · Eberhard et al., 2005 · Open in CIViC	civic
KRAS G12S	Erlotinib	Predictive	C	Supports Resistance	—	submitted	EID4017 In a prospective study of 522 European non-small cell lung cancer patients, patients with a KRAS exon 2 mutation (42/307) treated with erlotinib as a second-, third-line or more treatment were associa… (full text at CIViC) PMID 22982650 · Cadranel et al., 2012 · Open in CIViC	civic

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
12584	Pathogenic	criteria provided, multiple submitters, no conflicts	2	Gastric cancer; Non-small cell lung carcinoma; Juvenile myelomonocytic leukemia; Ovarian neoplasm; RASopathy; Vascular malformation; Neoplasm; Cardiofaciocutaneous syndrome 2; Rhabdomyosarcoma; Neuroblastoma; KRAS-related disorder	germline/somatic	13	May 12, 2025

Lung Squamous Cell Carcinoma1
KRAS G12S	Dasatinib	Predictive	D	Supports Resistance	—	submitted	EID4020 In an in vitro study, the A549 cell line, which harbors the KRAS G12S mutation, was found to have insensitivity to dasatinib treatment (IC50: 7.4 uM). In in vivo experiments, KRAS G12S expressing A549… (full text at CIViC) PMID 22328973 · Hammerman et al., 2011 · Open in CIViC	civic

Lung Squamous Cell Carcinoma1

KRAS G12S

Dasatinib

Predictive

Supports Resistance

—

submitted

EID4020

In an in vitro study, the A549 cell line, which harbors the KRAS G12S mutation, was found to have insensitivity to dasatinib treatment (IC50: 7.4 uM). In in vivo experiments, KRAS G12S expressing A549… (full text at CIViC)

PMID 22328973 · Hammerman et al., 2011 · Open in CIViC

Malignant Colorectal Neoplasm21
KRAS G12S	(diagnostic)	Diagnostic	B	Supports Positive	3	submitted	EID7168 G12S were associated with worse overall survival (2 to 3 fold increased risk for long term death) compared with patients with wtKRAS and were independent prognostic factors of worse OS of patients (Fi… (full text at CIViC) PMID 26038887 · Margonis et al., 2015 · Open in CIViC	civic
KRAS G12S	Cetuximab	Predictive	B	Supports Resistance	—	submitted	EID4005 In a retrospective study of 23 EGFR-expressing metastatic colorectal cancer patients, patients with KRAS codon G12 or G13 mutations (n=6) treated with cetuximab were associated with decreased partial … (full text at CIViC) PMID 17363584 · Benvenuti et al., 2007 · Open in CIViC	civic
KRAS G12S	Cetuximab	Predictive	B	Supports Resistance	3	accepted	EID4006 This was a retrospective study of 691 cetuximab treated patients with metastatic, chemotherapy refractory colorectal cancer. Of those, 16 patients harbored KRAS G12S, were BRAF, NRAS and PIK3CA wt, an… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
KRAS G12S	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID4000 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 G12S	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID4001 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 G12S	Cetuximab	Predictive	C	Supports Resistance	—	rejected	EID4002 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 G12S	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID4003 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 G12S	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID4004 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 G12S	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID4007 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 G12S	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID4008 In a retrospective study of 32 metastatic colorectal cancer patients, a patient with KRAS G12S mutation treated with cetuximab was reported to be a non-responder, whereas none of the 10 partial respon… (full text at CIViC) PMID 18669866 · Perrone et al., 2009 · Open in CIViC	civic
KRAS G12S	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID4009 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 G12S	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID4010 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 G12S	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID4011 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 G12S	Cetuximab + PanitumumabSubstitutes	Predictive	C	Supports Resistance	2	accepted	EID6314 In this study, a large cohort of metastatic colorectal cancer patients were treated with anti-epidermal growth factor receptor monoclonal antibodies (cetuximab or panitumumab). KRAS PIK3CA and PTEN we… (full text at CIViC) PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC	civic
KRAS G12S	Panitumumab	Predictive	C	Supports Resistance	—	accepted	EID2269 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 G12S	Panitumumab	Predictive	C	Supports Resistance	—	rejected	EID2270 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 16953233 · Oliveira et al., 2007 · Open in CIViC	civic
KRAS G12S	Panitumumab	Predictive	C	Supports Resistance	—	rejected	EID2271 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 2547513 · Bos, 1989 · Open in CIViC	civic
KRAS G12S	Panitumumab	Predictive	C	Supports Resistance	—	rejected	EID2272 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 8462792 · Benhattar et al., 1993 · Open in CIViC	civic
KRAS G12S	Cetuximab + PanitumumabSubstitutes	Predictive	C	Does Not Support Resistance	1	rejected	EID6324 In this study, a large cohort of metastatic colorectal cancer patients were treated with anti-epidermal growth factor receptor monoclonal antibodies (cetuximab or panitumumab). KRAS G12S was the only … (full text at CIViC) PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC	civic
KRAS G12S	Regorafenib Anhydrous	Predictive	D	Supports Resistance	2	accepted	EID4012 In an in vitro study, a human colon adenocarcinoma SW48 cell line expressing KRAS G12S mutation demonstrated resistance to regorafenib treatment (IC50: 264.23 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 G12S	Sunitinib	Predictive	D	Supports Resistance	—	submitted	EID4014 In an in vitro study, colorectal cancer SW48 cell line expressing KRAS G12S mutation demonstrated reduced sensitivity to sunitinib treatment (IC50: 6.7uM 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

Multiple Myeloma6
KRAS G12S	Melphalan	Predictive	B	Supports Resistance	2	rejected	EID2274 In a study of patients receiving melphalan-based therapy, those with KRAS codon 12 mutations were less likely to have a positive response than those with wildtype KRAS (26.9% vs. 58.3%, P=0.015). PMID 19284554 · Greco et al., 2009 · Open in CIViC	civic
KRAS G12S	Melphalan	Predictive	B	Supports Resistance	—	submitted	EID2275 Activating mutations in KRAS or NRAS were observed more frequently in multiple myeloma patients than in patients with monoclonal gammopathy of uncertain significance (MGUS) (31% vs. 5% ). Another stu… (full text at CIViC) PMID 11524732 · Bezieau et al., 2001 · Open in CIViC	civic
KRAS G12S	Melphalan	Predictive	B	Supports Resistance	—	submitted	EID2276 Activating mutations in KRAS or NRAS were observed more frequently in multiple myeloma patients than in patients with monoclonal gammopathy of uncertain significance (MGUS) (31% vs. 5% ). Another stu… (full text at CIViC) PMID 15339850 · Rasmussen et al., 2005 · Open in CIViC	civic
KRAS G12S	Melphalan	Predictive	D	Supports Resistance	2	accepted	EID2277 In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in compariso… (full text at CIViC) PMID 11050000 · Rowley et al., 2000 · Open in CIViC	civic
KRAS G12S	Melphalan	Predictive	D	Supports Resistance	2	accepted	EID2278 In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in compariso… (full text at CIViC) PMID 12483530 · Rowley et al., 2002 · Open in CIViC	civic
KRAS G12S	Melphalan	Predictive	D	Supports Resistance	2	accepted	EID2279 In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less sensitive to the apoptosis-inducing effects of dexamethasone, doxorubicin, and melphalan in compariso… (full text at CIViC) PMID 16497971 · Hoang et al., 2006 · Open in CIViC	civic