Variant · Snv

NRAS Q61R

CI-VAR-00003573Explore in graph →NP_002515.1:p.Gln61ArgNM_002524.4:c.182A>GClinVar 13900 CIViC 96 rs11554290

Curated evidence

Evidence by cancer (16 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 1–16 of 16 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
Cutaneous Melanoma1
NRAS Q61R	Vemurafenib	Predictive	D	Supports Resistance	—	submitted	EID3830 In an in vitro study of single-cell clones derived from a cutaneous melanoma patient expressing a BRAF V600E mutation (a known sensitizing mutation to vemurafenib) and NRAS Q61R co-mutations, NRAS Q61… (full text at CIViC) PMID 23948972 · Romano et al., 2013 · Open in CIViC	civic
Lung Non-Small Cell Carcinoma1
NRAS Q61R	Selumetinib + TrametinibSubstitutes	Predictive	D	Supports Sensitivity Response	2	submitted	EID3019 Of the 4,562 patients with lung cancers, 30 showed NRAS mutations, which corresponded to 9 different amino acid substitutions. Cell lines were developed for 6 of these mutations and 5/6 were sensitivi…

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
13900	Pathogenic	criteria provided, multiple submitters, no conflicts	2	Thyroid cancer, nonmedullary, 2; Epidermal nevus; Non-small cell lung carcinoma; Large congenital melanocytic nevus; Neurocutaneous melanocytosis; Linear nevus sebaceous syndrome; Noonan syndrome 6; Neoplasm; Vascular malformation; Nodal T-follicular helper cell lymphoma; Diffuse midline glioma, H3 K27M-mutant; Colorectal cancer; Embryonal rhabdomyosarcoma; Melanoma; Germinoma; Follicular thyroid carcinoma; NRAS-related disorder

Malignant Colorectal Neoplasm5
NRAS Q61R	Cetuximab	Predictive	C	Supports Resistance	2	accepted	EID2184 Five patients participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had tumors which harbored NRAS Q61R and were wildtype for KRAS, BRAF and P… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
NRAS Q61R	Cetuximab	Predictive	D	Supports Resistance	—	submitted	EID3828 In 28 out of 40 (70%) metastatic colorectal cancer tumors implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/mTor inhibitor BEZ235 resulted in disease stabiliza… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC	civic
NRAS Q61R	Dactolisib	Predictive	C	Supports Sensitivity Response	—	rejected	EID2188 NRAS mutations have also been observed in melanoma and biliary tract, bladder, cervix, liver, lung, myeloid leukemia, ovarian, pancreatic, and thyroid cancer. PMID 17384584 · Schubbert et al., 2007 · Open in CIViC	civic
NRAS Q61R	Dactolisib	Predictive	D	Supports Sensitivity Response	—	submitted	EID2186 In 28 out of 40 (70%) metastatic colorectal cancer tumors implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/mTor inhibitor BEZ235 resulted in disease stabiliza… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC	civic
NRAS Q61R	Selumetinib	Predictive	C	Supports Sensitivity Response	—	rejected	EID2185 NRAS mutations have also been observed in melanoma and biliary tract, bladder, cervix, liver, lung, myeloid leukemia, ovarian, pancreatic, and thyroid cancer. PMID 17384584 · Schubbert et al., 2007 · Open in CIViC	civic

Malignant Colorectal Neoplasm5

NRAS Q61R

Cetuximab

Predictive

Supports Resistance

accepted

EID2184

Five patients participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had tumors which harbored NRAS Q61R and were wildtype for KRAS, BRAF and P… (full text at CIViC)

PMID 20619739 · De Roock et al., 2010 · Open in CIViC

civic

NRAS Q61R

Cetuximab

Predictive

Supports Resistance

—

submitted

EID3828

In 28 out of 40 (70%) metastatic colorectal cancer tumors implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/mTor inhibitor BEZ235 resulted in disease stabiliza… (full text at CIViC)

PMID 22392911 · Migliardi et al., 2012 · Open in CIViC

civic

NRAS Q61R

Dactolisib

Predictive

Supports Sensitivity Response

—

rejected

EID2188

NRAS mutations have also been observed in melanoma and biliary tract, bladder, cervix, liver, lung, myeloid leukemia, ovarian, pancreatic, and thyroid cancer.

PMID 17384584 · Schubbert et al., 2007 · Open in CIViC

civic

NRAS Q61R

Dactolisib

Predictive

Supports Sensitivity Response

—

submitted

EID2186

PMID 22392911 · Migliardi et al., 2012 · Open in CIViC

civic

NRAS Q61R

Selumetinib

Predictive

Supports Sensitivity Response

—

rejected

EID2185

NRAS mutations have also been observed in melanoma and biliary tract, bladder, cervix, liver, lung, myeloid leukemia, ovarian, pancreatic, and thyroid cancer.

PMID 17384584 · Schubbert et al., 2007 · Open in CIViC

civic

Malignant Neoplasm1
NRAS Q61R	Vemurafenib	Predictive	D	Supports Resistance	3	submitted	EID12438 Several BRAF mutant cell lines were treated with vemurafenib, A375 (BRAF V600E) was used as a positive control. The SK-MEL-2 cell line (NRAS Q61R) was not inhibited. PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic

Malignant Neoplasm1

NRAS Q61R

Vemurafenib

Predictive

Supports Resistance

submitted

EID12438

Several BRAF mutant cell lines were treated with vemurafenib, A375 (BRAF V600E) was used as a positive control. The SK-MEL-2 cell line (NRAS Q61R) was not inhibited.

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic

Melanoma5
NRAS Q61R	Belvarafenib	Predictive	C	Supports Resistance	2	submitted	EID13219 A patient with cutaneous melanoma harboring NRAS Q61R received belvarafenib monotherapy after two prior lines of systemic therapy and had progressive disease as the best RECIST response. The patient r… (full text at CIViC) PMID 38470950 · Kim et al., 2024 · Open in CIViC	civic
NRAS Q61R	Belvarafenib	Predictive	C	Supports Sensitivity Response	2	accepted	EID13220 A patient with melanoma harboring NRAS Q61R received belvarafenib monotherapy after one prior line of systemic therapy and achieved stable disease as the best RECIST response. At the October 2023 data… (full text at CIViC) PMID 38470950 · Kim et al., 2024 · Open in CIViC	civic
NRAS Q61R	Pan-RAF/MEK Molecular Glue NST-628	Predictive	D	Supports Sensitivity Response	4	submitted	EID13155 In NRAS Q61R-mutant SK-MEL-2 melanoma cells, NST-628 showed potent antiproliferative activity, increased apoptosis, and durably suppressed MAPK-pathway signaling. In an intracranial SK-MEL-2-luc xenog… (full text at CIViC) PMID 38588399 · Ryan et al., 2024 · Open in CIViC	civic
NRAS Q61R	Temozolomide	Predictive	C	Supports Sensitivity Response	2	accepted	EID23 In a melanoma patient with Q61R mutation, treatment with temozolomide resulted in overall survival of 16 months. PMID 21576590 · Soon et al., 2011 · Open in CIViC	civic
NRAS Q61R	Vemurafenib	Predictive	C	Supports Resistance	—	submitted	EID3829 In a retrospective study of 44 malignant melanoma patients, NRAS Q61R was associated with acquired resistance to vemurafenib monotherapy in three patients with disease progressive tumors harboring NRA… (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC	civic

Melanoma5

NRAS Q61R

Belvarafenib

Predictive

Supports Resistance

submitted

EID13219

A patient with cutaneous melanoma harboring NRAS Q61R received belvarafenib monotherapy after two prior lines of systemic therapy and had progressive disease as the best RECIST response. The patient r… (full text at CIViC)

PMID 38470950 · Kim et al., 2024 · Open in CIViC

civic

NRAS Q61R

Belvarafenib

Predictive

Supports Sensitivity Response

accepted

EID13220

A patient with melanoma harboring NRAS Q61R received belvarafenib monotherapy after one prior line of systemic therapy and achieved stable disease as the best RECIST response. At the October 2023 data… (full text at CIViC)

PMID 38470950 · Kim et al., 2024 · Open in CIViC

civic

NRAS Q61R

Pan-RAF/MEK Molecular Glue NST-628

Predictive

Supports Sensitivity Response

submitted

EID13155

In NRAS Q61R-mutant SK-MEL-2 melanoma cells, NST-628 showed potent antiproliferative activity, increased apoptosis, and durably suppressed MAPK-pathway signaling. In an intracranial SK-MEL-2-luc xenog… (full text at CIViC)

PMID 38588399 · Ryan et al., 2024 · Open in CIViC

civic

NRAS Q61R

Temozolomide

Predictive

Supports Sensitivity Response

accepted

EID23

In a melanoma patient with Q61R mutation, treatment with temozolomide resulted in overall survival of 16 months.

PMID 21576590 · Soon et al., 2011 · Open in CIViC

civic

NRAS Q61R

Vemurafenib

Predictive

Supports Resistance

—

submitted

EID3829

In a retrospective study of 44 malignant melanoma patients, NRAS Q61R was associated with acquired resistance to vemurafenib monotherapy in three patients with disease progressive tumors harboring NRA… (full text at CIViC)

PMID 24265155 · Shi et al., 2014 · Open in CIViC

civic

Thyroid Gland Carcinoma1
NRAS Q61R	Vemurafenib	Predictive	D	Supports Resistance	—	submitted	EID3831 In an in vitro study, a HTH7 cell line expressing NRAS Q61R demonstrated reduced sensitivity to vemurafenib treatment, compared to BRAF V600E expressing cells (8505C, SWI1736, BHT101 and BCPAP). Sensi… (full text at CIViC) PMID 19880792 · Salerno et al., 2010 · Open in CIViC	civic

Thyroid Gland Carcinoma1

NRAS Q61R

Vemurafenib

Predictive

Supports Resistance

—

submitted

EID3831

In an in vitro study, a HTH7 cell line expressing NRAS Q61R demonstrated reduced sensitivity to vemurafenib treatment, compared to BRAF V600E expressing cells (8505C, SWI1736, BHT101 and BCPAP). Sensi… (full text at CIViC)

PMID 19880792 · Salerno et al., 2010 · Open in CIViC

civic

Unmapped disease2unmapped disease
NRAS Q61R	(functional)	Functional	D	Supports Gain Of Function	5	submitted	EID12978 NRAS p.Gln61Arg (NM_002524.5:c.182A>G) causes decreased GTPase activity, and impaired nucleotide exchange. PMID 25252692 · Burd et al., 2014 · Open in CIViC	civic
NRAS Q61R	(functional)	Functional	D	Supports Gain Of Function	5	submitted	EID12979 NRAS p.Gln61Arg (NM_002524.5:c.182A>G) causes increased pERK/ERK ratio, and increased BRAF binding affinity. PMID 35672316 · Murphy et al., 2022 · Open in CIViC	civic

Unmapped disease2unmapped disease

NRAS Q61R

(functional)

Functional

Supports Gain Of Function

submitted

EID12978

NRAS p.Gln61Arg (NM_002524.5:c.182A>G) causes decreased GTPase activity, and impaired nucleotide exchange.

PMID 25252692 · Burd et al., 2014 · Open in CIViC

civic

NRAS Q61R

(functional)

Functional

Supports Gain Of Function

submitted

EID12979

NRAS p.Gln61Arg (NM_002524.5:c.182A>G) causes increased pERK/ERK ratio, and increased BRAF binding affinity.

PMID 35672316 · Murphy et al., 2022 · Open in CIViC

civic