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 51–65 of 65 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
Malignant Neoplasm2
KRAS G12C	ARS-853 + Epidermal Growth Factor Receptor Tyrosine Kinase InhibitorCombination	Predictive	D	Supports Sensitivity Response	3	accepted	EID1173 Preclinical study to investigate mechanisms of KRAS G12C activity and inhibition with ARS-853, a covalent (irreversible) inhibitor which binds KRAS G12C in the GDP-bound state to prevent activation. R… (full text at CIViC) PMID 26739882 · Patricelli et al., 2016 · Open in CIViC	civic
KRAS G12C	Sotorasib	Predictive	B	Supports Sensitivity Response	5	submitted	EID8068 In preclinical analyses, treatment with AMG 510 led to the regression of KRASG12C tumours and improved the anti-tumour efficacy of chemotherapy and targeted agents. In immune-competent mice, treatment… (full text at CIViC) PMID ·

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 Pancreatic Neoplasm1
KRAS G12C	Sotorasib	Predictive	B	Supports Sensitivity Response	3	submitted	EID11680 In this phase 1/2 trial the safety and efficacy of sotorasib was assessed in patients with KRAS G12C mutated metastatic pancreatic cancer who had previously received at least one line of systemic ther… (full text at CIViC) PMID 36546651 · Strickler et al., 2023 · Open in CIViC	civic

Malignant Pancreatic Neoplasm1

KRAS G12C

Sotorasib

Predictive

Supports Sensitivity Response

submitted

EID11680

In this phase 1/2 trial the safety and efficacy of sotorasib was assessed in patients with KRAS G12C mutated metastatic pancreatic cancer who had previously received at least one line of systemic ther… (full text at CIViC)

PMID 36546651 · Strickler et al., 2023 · Open in CIViC

civic

Multiple Myeloma6
KRAS G12C	Melphalan	Predictive	B	Supports Resistance	2	rejected	EID2258 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 G12C	Melphalan	Predictive	B	Supports Resistance	—	submitted	EID2259 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 G12C	Melphalan	Predictive	B	Supports Resistance	—	submitted	EID2260 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 G12C	Melphalan	Predictive	D	Supports Resistance	2	accepted	EID2261 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 G12C	Melphalan	Predictive	D	Supports Resistance	—	accepted	EID2262 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 G12C	Melphalan	Predictive	D	Supports Resistance	2	accepted	EID2263 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

Multiple Myeloma6

KRAS G12C

Melphalan

Predictive

Supports Resistance

rejected

EID2258

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 G12C

Melphalan

Predictive

Supports Resistance

—

submitted

EID2259

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 G12C

Melphalan

Predictive

Supports Resistance

—

submitted

EID2260

PMID 15339850 · Rasmussen et al., 2005 · Open in CIViC

civic

KRAS G12C

Melphalan

Predictive

Supports Resistance

accepted

EID2261

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 G12C

Melphalan

Predictive

Supports Resistance

—

accepted

EID2262

PMID 12483530 · Rowley et al., 2002 · Open in CIViC

civic

KRAS G12C

Melphalan

Predictive

Supports Resistance

accepted

EID2263

PMID 16497971 · Hoang et al., 2006 · Open in CIViC

civic

Pancreatic Ductal Adenocarcinoma2
ERBB2 V777L AND KRAS G12C	ARS-1620 + NeratinibCombination	Predictive	D	Supports Sensitivity Response	3	submitted	EID11572 When tested in MIAPaCa2 (PDAC cell line and KRAS G12C) cells, Neratinib and ARS-1620 strongly inhibit AKT and MAPK phosphorylation (Figure 6F). Also, MIAPaCa2 cell line with the variant in exposure to… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC	civic
KRAS G12C AND ERBB2 V842I	ARS-1620 + NeratinibCombination	Predictive	D	Supports Sensitivity Response	3	submitted	EID11573 When tested in MIAPaCa2 (PDAC cell line and KRAS G12C) cells, Neratinib and ARS-1620 strongly inhibit AKT and MAPK phosphorylation (Figure 6F). Also, MIAPaCa2 cell line with the variant in exposure to… (full text at CIViC) PMID 31046123 · Li et al., 2020 · Open in CIViC	civic

Pancreatic Ductal Adenocarcinoma2

ERBB2 V777L AND KRAS G12C

ARS-1620 + NeratinibCombination

Predictive

Supports Sensitivity Response

submitted

EID11572

When tested in MIAPaCa2 (PDAC cell line and KRAS G12C) cells, Neratinib and ARS-1620 strongly inhibit AKT and MAPK phosphorylation (Figure 6F). Also, MIAPaCa2 cell line with the variant in exposure to… (full text at CIViC)

PMID 31046123 · Li et al., 2020 · Open in CIViC

civic

KRAS G12C AND ERBB2 V842I

ARS-1620 + NeratinibCombination

Predictive

Supports Sensitivity Response

submitted

EID11573

PMID 31046123 · Li et al., 2020 · Open in CIViC

civic

Skin Squamous Cell Carcinoma1
KRAS G12C	Vemurafenib	Predictive	C	Supports Resistance	—	submitted	EID3982 In a retrospective study of 23 patients with BRAF V600 mutation (a known vemurafenib sensitizing mutation) that developed cutaneous squamous-cell carcinoma upon treatment with vemurafenib monotherapy,… (full text at CIViC) PMID 22256804 · Su et al., 2012 · Open in CIViC	civic

Skin Squamous Cell Carcinoma1

KRAS G12C

Vemurafenib

Predictive

Supports Resistance

—

submitted

EID3982

In a retrospective study of 23 patients with BRAF V600 mutation (a known vemurafenib sensitizing mutation) that developed cutaneous squamous-cell carcinoma upon treatment with vemurafenib monotherapy,… (full text at CIViC)

PMID 22256804 · Su et al., 2012 · Open in CIViC

civic

Solid Neoplasm1
KRAS G12C	Adagrasib	Predictive	D	Supports Sensitivity Response	3	accepted	EID7572 In cell lines, MRTX849 inhibits growth and viability of cells harboring KRAS G12C mutations, but not in cells with other mutant forms or of wild-type KRAS. In animal models, MRTX849 demonstrates anti… (full text at CIViC) Open in CIViC	civic

Solid Neoplasm1

KRAS G12C

Adagrasib

Predictive

Supports Sensitivity Response

accepted

EID7572

In cell lines, MRTX849 inhibits growth and viability of cells harboring KRAS G12C mutations, but not in cells with other mutant forms or of wild-type KRAS. In animal models, MRTX849 demonstrates anti… (full text at CIViC)

Open in CIViC

civic

Solid Tumors, Advanced2unmapped disease
KRAS G12C	Sotorasib	Predictive	B	Supports Sensitivity Response	3	submitted	EID10110 Based on a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation, sotorasib (a small molecule that selectively and irreversibly targets KRAS p.G12C) show… (full text at CIViC) PMID 32955176 · Hong et al., 2020 · Open in CIViC	civic
KRAS G12C OR KRAS G12D OR KRAS G13D OR RET M918T OR KRAS G12A OR KRAS G12V OR KRAS G12R OR KRAS Amplification OR KRAS G12S OR KRAS G13R OR KRAS G12P	Sorafenib	Predictive	B	Supports Sensitivity Response	3	submitted	EID12700 In the randomized discontinuation Phase II MOST-Plus trial of advanced/metastatic solid tumors with sorafenib-targeted somatic alterations (NCT02029001; n = 35 randomized; KRAS G12A/C/D/P/R/S/V n = 29… (full text at CIViC) PMID 37444551 · Trédan et al., 2023 · Open in CIViC	civic

Solid Tumors, Advanced2unmapped disease

KRAS G12C

Sotorasib

Predictive

Supports Sensitivity Response

submitted

EID10110

Based on a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation, sotorasib (a small molecule that selectively and irreversibly targets KRAS p.G12C) show… (full text at CIViC)

PMID 32955176 · Hong et al., 2020 · Open in CIViC

civic

KRAS G12C OR KRAS G12D OR KRAS G13D OR RET M918T OR KRAS G12A OR KRAS G12V OR KRAS G12R OR KRAS Amplification OR KRAS G12S OR KRAS G13R OR KRAS G12P

Sorafenib

Predictive

Supports Sensitivity Response

submitted

EID12700

In the randomized discontinuation Phase II MOST-Plus trial of advanced/metastatic solid tumors with sorafenib-targeted somatic alterations (NCT02029001; n = 35 randomized; KRAS G12A/C/D/P/R/S/V n = 29… (full text at CIViC)

PMID 37444551 · Trédan et al., 2023 · Open in CIViC

civic