Variant · Snv

KRAS G12D

CI-VAR-00001606Explore in graph →NP_004976.2:p.Gly12AspNM_004985.4:c.35G>AClinVar 12582 CIViC 79 rs121913529

Curated evidence

Evidence by cancer (81 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 81 evidence items across 8 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
Hairy Cell Leukemia1
KRAS G12D	Vemurafenib	Predictive	C	Supports Resistance	2	accepted	EID1580 One patient enrolled in a clinical study to evaluate vemurafenib treatment of BRAF V600E mutant hairy-cell leukemia developed resistance to vemurafenib retreatment. 300-gene targeted sequencing of the… (full text at CIViC) PMID 26352686 · Tiacci et al., 2015 · Open in CIViC	civic
Lung Adenocarcinoma4
KRAS G12D	Dabrafenib	Predictive	C	Supports Resistance	2	accepted	EID91 A 63 year old patient was diagnosed with lung adenocarcinoma and received several treatment regimens over approximately three years, including carboplatin/paclitaxel, erlotinib, pemetrexed/bevacizumab… (full text at CIViC) PMID 23524406 ·

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
12582	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts	2	Carcinoma of pancreas; Epidermal nevus; Nevus sebaceous; Linear nevus sebaceous syndrome; Juvenile myelomonocytic leukemia; Non-small cell lung carcinoma; Ovarian neoplasm; Acute myeloid leukemia; RASopathy; Cerebral arteriovenous malformation; Vascular Tumors Including Pyogenic Granuloma; Primary low grade serous adenocarcinoma of ovary; Encephalocraniocutaneous lipomatosis; Capillary malformation-arteriovenous malformation 1; Gastric cancer; Congenital Pulmonary Airway Malformations; Atypical endometrial hyperplasia; Endometrial hyperplasia without atypia; Neoplasm; Cardiovascular phenotype; Adenocarcinoma of the large intestine; Ovarian mucinous adenocarcinoma; Precursor B-cell acute lymphoblastic leukemia; Diffuse midline glioma, H3 K27M-mutant; Colorectal cancer; Medulloblastoma non-WNT/non-SHH; Glioma; RAS-ASSOCIATED AUTOIMMUNE LEUKOPROLIFERATIVE DISORDER 2, SOMATIC; Embryonal rhabdomyosarcoma; Papillary thyroid carcinoma; Alveolar rhabdomyosarcoma; Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype; KRAS-related disorder

Lung Non-Small Cell Carcinoma3
KRAS G12D	Erlotinib	Predictive	C	Supports Resistance	—	submitted	EID3955 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
KRAS G12D	KRAS G12D Inhibitor HRS-4642	Predictive	B	Supports Sensitivity Response	3	submitted	EID12137 Zhou, C., et al. developed a novel KRAS G12D inhibitor, HRS-4642, and found that in preclincial experiments, HRS-4642 effectively reduced tumor growth compared to controls. After preclinical success, … (full text at CIViC) PMID 38942026 · Zhou et al., 2024 · Open in CIViC	civic
KRAS G12D	Setidegrasib	Predictive	B	Supports Sensitivity Response	3	submitted	EID12937 A phase 1 dose‑escalation and dose‑expansion study in patients with previously treated advanced KRAS p.G12D mutant NSCLC (NCT05382559; n = 203 overall; n = 45 NSCLC treated at the recommended phase 2 … (full text at CIViC) PMID 41879829 · Park et al., 2026 · Open in CIViC	civic

Malignant Colorectal Neoplasm27
KRAS G12D	(prognostic)	Prognostic	B	Supports Better Outcome	3	accepted	EID1215 In 119 metastatic colorectal cancer patients treated with cetuximab-based first-line chemotherapy, KRAS G12D mutations (N=44) were associated with longer overall patient survival when compared to othe… (full text at CIViC) PMID 22948721 · Modest et al., 2012 · Open in CIViC	civic
KRAS G12D	(diagnostic)	Diagnostic	B	Supports Positive	4	submitted	EID8031 Jens Neumann et al analyzed 1018 cases of metastatic colorectal cancer. They focused on KRAS mutation of codons 12 and 13. Direct genomic sequencing was applied to detect the KRAS mutation. After the … (full text at CIViC) PMID 19679400 · Neumann et al., 2009 · Open in CIViC	civic
KRAS G12D	Bevacizumab + Binimetinib + HydroxychloroquineCombination	Predictive	C	Supports Sensitivity Response	2	submitted	EID10797 Case report of a 41-year-old female with T4N2M1 sigmoid adenocarcinoma with KRAS G12D mutation. After progression on FOLFOX, XELOX plus bevacizumab and capecitabine plus bevacizumab. After progression… (full text at CIViC) PMID 32999660 · Orlov et al., 2020 · Open in CIViC	civic
KRAS G12D	Cetuximab	Predictive	B	Supports Resistance	3	accepted	EID2207 This was a retrospective study of 691 cetuximab treated patients with metastatic colorectal cancer. Of those, 76 patients harbored KRAS G12D, were BRAF, NRAS and PIK3CA wt, and had individual response… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
KRAS G12D	Cetuximab	Predictive	B	Supports Resistance	—	submitted	EID3938 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 G12D	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3933 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 G12D	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3934 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 G12D	Cetuximab	Predictive	C	Supports Resistance	—	rejected	EID3935 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 G12D	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3936 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 G12D	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3937 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 G12D	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3940 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 G12D	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3941 In a retrospective study of 32 metastatic colorectal cancer patients, patients with KRAS G12D (n=2) mutation treated with cetuximab were reported to be non-responders. None of the 10 partial responder… (full text at CIViC) PMID 18669866 · Perrone et al., 2009 · Open in CIViC	civic
KRAS G12D	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3942 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 G12D	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3943 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 G12D	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3944 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 G12D	Cetuximab	Predictive	C	Supports Resistance	—	submitted	EID3945 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 G12D	Dactolisib + SelumetinibCombination	Predictive	D	Supports Sensitivity Response	3	accepted	EID2218 In 28 out of 40 (70%) metastatic colorectal cancer tumors harboring KRAS, NRAS, BRAF 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 G12D	Panitumumab	Predictive	C	Supports Resistance	3	accepted	EID2193 One patient participating in a large retrospective study of EGFR monoclonal antibodies in metastatic, treatment refractory colorectal cancer had a tumor which harbored KRAS G12D, was wildtype for NRAS… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
KRAS G12D	Panitumumab	Predictive	C	Supports Resistance	—	accepted	EID2236 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 G12D	Panitumumab	Predictive	C	Supports Resistance	—	submitted	EID2237 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 16953233 · Oliveira et al., 2007 · Open in CIViC	civic
KRAS G12D	Panitumumab	Predictive	C	Supports Resistance	—	submitted	EID2238 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 2547513 · Bos, 1989 · Open in CIViC	civic
KRAS G12D	Panitumumab	Predictive	C	Supports Resistance	—	submitted	EID2239 KRAS mutations have been reported in 30-50% of colorectal carcinomas. PMID 8462792 · Benhattar et al., 1993 · Open in CIViC	civic
KRAS G12D	Cetuximab + PanitumumabSubstitutes	Predictive	C	Supports Resistance	2	accepted	EID6316 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 … (full text at CIViC) PMID 19223544 · Sartore-Bianchi et al., 2009 · Open in CIViC	civic
KRAS G12D	Regorafenib Anhydrous	Predictive	C	Supports Resistance	—	submitted	EID3947 In a stage IIA (T3N0M0) sigmoid colorectal cancer patient with multiple lung metastases harboring KRAS G12D mutation, a partial response to regorafenib monotherapy was reported. The patient was treate… (full text at CIViC) PMID 26870193 · Kawasaki et al., 2016 · Open in CIViC	civic
KRAS G12D	Regorafenib Anhydrous	Predictive	D	Supports Resistance	1	accepted	EID3946 In an in vitro study, a human colon adenocarcinoma SW48 cell line expressing KRAS G12D mutation demonstrated resistance to regorafenib treatment (IC50: 195.01nM vs. 114.28 nM P<0.01) compared to SW48 … (full text at CIViC) PMID 26161928 · Camaj et al., 2015 · Open in CIViC	civic
KRAS G12D	Sunitinib	Predictive	D	Supports Resistance	—	submitted	EID3948 In an in vitro study, colorectal cancer SW48 cell line expressing KRAS G12D mutation demonstrated reduced sensitivity to sunitinib treatment (IC50: 4.9uM 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
KRAS G12D	Therapeutic Tumor Infiltrating Lymphocytes	Predictive	C	Supports Sensitivity Response	3	accepted	EID1898 A patient with metastatic colorectal cancer was enrolled in a phase 2 clinical trial (NCT01174121). 24 cultures of tumor-infiltrating lymphocytes were expanded from 3 lung metastasis resections. After… (full text at CIViC) PMID 27959684 · Tran et al., 2016 · Open in CIViC	civic