This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 61 of the NRAS protein (p.Gln61Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NRAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 375874). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NRAS protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Uncertain significance
- Review status:
- criteria provided, single submitter
- Submissions:
- 20
- First in ClinVar:
- Mar 8, 2017
- Most recent Submission:
- Feb 7, 2023
- Last evaluated:
- Mar 12, 2022
- Accession:
- VCV000375874.3
- Variation ID:
- 375874
- Description:
- single nucleotide variant
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NM_002524.5(NRAS):c.182A>T (p.Gln61Leu)
- Allele ID
- 362753
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 1p13.2
- Genomic location
- 1: 114713908 (GRCh38) GRCh38 UCSC
- 1: 115256529 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_002524.5:c.182A>T MANE Select NP_002515.1:p.Gln61Leu missense NC_000001.11:g.114713908T>A NC_000001.10:g.115256529T>A NG_007572.1:g.7987A>T LRG_92:g.7987A>T - Protein change
- Q61L
- Other names
- -
- Canonical SPDI
- NC_000001.11:114713907:T:A
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- ClinGen: CA16602361
- dbSNP: rs11554290
- VarSome
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Uncertain significance | 1 | criteria provided, single submitter | Mar 12, 2022 | RCV002524687.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000423898.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000424084.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000426122.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000418396.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000418220.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000433349.1 | |
| Pathogenic | 1 | no assertion criteria provided | Oct 2, 2014 | RCV000435412.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000422640.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000435905.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000429082.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000438738.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000428055.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000441171.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000433761.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000431333.1 | |
| Pathogenic | 1 | no assertion criteria provided | Mar 10, 2016 | RCV000436539.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000444188.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000444754.1 | |
| Likely pathogenic | 1 | no assertion criteria provided | May 31, 2016 | RCV000444899.1 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Uncertain significance
(Mar 12, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
RASopathy
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV003296678.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 61 of the NRAS protein (p.Gln61Leu). … (more)
This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 61 of the NRAS protein (p.Gln61Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NRAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 375874). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NRAS protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
|
|
|
Pathogenic
(Mar 10, 2016)
|
no assertion criteria provided
Method: literature only
|
Melanoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503592.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Multiple myeloma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503597.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Neoplasm of the large intestine
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503593.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Ovarian serous cystadenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503594.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Pathogenic
(Oct 02, 2014)
|
no assertion criteria provided
Method: literature only
|
Non-small cell lung carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503595.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Malignant neoplasm of body of uterus
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503596.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Transitional cell carcinoma of the bladder
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503598.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
B-cell chronic lymphocytic leukemia
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503603.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Acute myeloid leukemia
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503599.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Thyroid tumor
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503600.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
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Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Neoplasm of brain
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503601.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
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|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Hepatocellular carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503602.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Gastric adenocarcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503604.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Glioblastoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503605.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Adrenal cortex carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503610.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Malignant melanoma of skin
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503609.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
None
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503606.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Nasopharyngeal neoplasm
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503607.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(May 31, 2016)
|
no assertion criteria provided
Method: literature only
|
Renal cell carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Database of Curated Mutations (DoCM)
Accession: SCV000503608.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
Functional evidence
Help| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity. | Chang MT | Nature biotechnology | 2016 | PMID: 26619011 |
| Prospective enterprise-level molecular genotyping of a cohort of cancer patients. | MacConaill LE | The Journal of molecular diagnostics : JMD | 2014 | PMID: 25157968 |
| Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. | Morris EJ | Cancer discovery | 2013 | PMID: 23614898 |
| Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma. | Trunzer K | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2013 | PMID: 23569304 |
| Inhibition of Wee1, AKT, and CDK4 underlies the efficacy of the HSP90 inhibitor XL888 in an in vivo model of NRAS-mutant melanoma. | Haarberg HE | Molecular cancer therapeutics | 2013 | PMID: 23538902 |
| Characteristics of lung cancers harboring NRAS mutations. | Ohashi K | Clinical cancer research : an official journal of the American Association for Cancer Research | 2013 | PMID: 23515407 |
| MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. | Ascierto PA | The Lancet. Oncology | 2013 | PMID: 23414587 |
| First-in-human, phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of RO5126766, a first-in-class dual MEK/RAF inhibitor in patients with solid tumors. | Martinez-Garcia M | Clinical cancer research : an official journal of the American Association for Cancer Research | 2012 | PMID: 22761467 |
| NRAS-mutant melanoma: response to chemotherapy. | Soon CW | Archives of dermatology | 2011 | PMID: 21576590 |
| Differential sensitivity of melanoma cell lines with BRAFV600E mutation to the specific Raf inhibitor PLX4032. | Søndergaard JN | Journal of translational medicine | 2010 | PMID: 20406486 |
| RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. | Poulikakos PI | Nature | 2010 | PMID: 20179705 |
| PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells. | Halaban R | Pigment cell & melanoma research | 2010 | PMID: 20149136 |
| RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. | Hatzivassiliou G | Nature | 2010 | PMID: 20130576 |
| Somatic mutations affect key pathways in lung adenocarcinoma. | Ding L | Nature | 2008 | PMID: 18948947 |
| Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers. | Adjei AA | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2008 | PMID: 18390968 |
| Distinct sets of genetic alterations in melanoma. | Curtin JA | The New England journal of medicine | 2005 | PMID: 16291983 |
| BRAF and RAS mutations in human lung cancer and melanoma. | Brose MS | Cancer research | 2002 | PMID: 12460918 |
| Ras mutations in human melanoma: a marker of malignant progression. | Ball NJ | The Journal of investigative dermatology | 1994 | PMID: 8120410 |
| N-ras mutations in human cutaneous melanoma from sun-exposed body sites. | van 't Veer LJ | Molecular and cellular biology | 1989 | PMID: 2674680 |
| http://docm.genome.wustl.edu/variants/ENST00000369535:c.182A>T | - | - | - | - |
Text-mined citations for rs11554290...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Apr 15, 2023