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NM_005228.5(EGFR):c.2573T>G (p.Leu858Arg)

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Interpretation:
drug response​

Review status:
reviewed by expert panel
Submissions:
8 (Most recent: Jun 18, 2018)
Last evaluated:
Mar 21, 2018
Accession:
VCV000016609.2
Variation ID:
16609
Description:
single nucleotide variant
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NM_005228.5(EGFR):c.2573T>G (p.Leu858Arg)

Allele ID
31648
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
7p11.2
Genomic location
7: 55191822 (GRCh38) GRCh38 UCSC
7: 55259515 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000007.14:g.55191822T>G
NC_000007.13:g.55259515T>G
LRG_304t1:c.2573T>G LRG_304p1:p.Leu858Arg
... more HGVS
Protein change
L858R
Other names
-
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
PharmGKB Clinical Annotation: 981420042
PharmGKB Clinical Annotation: 981475838
PharmGKB Clinical Annotation: 981475880
UniProtKB: P00533#VAR_019298
OMIM: 131550.0002
dbSNP: rs121434568
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
drug response 1 reviewed by expert panel Oct 27, 2015 RCV000211235.1
drug response 1 reviewed by expert panel Mar 21, 2018 RCV000211323.1
drug response 1 reviewed by expert panel Apr 7, 2016 RCV000211410.1
drug response 1 no assertion criteria provided May 19, 2005 RCV000018083.89
drug response 1 no assertion criteria provided May 19, 2005 RCV000018084.63
drug response 1 no assertion criteria provided Oct 28, 2006 RCV000150629.1
Likely pathogenic 1 no assertion criteria provided May 31, 2016 RCV000418019.1
Pathogenic 1 no assertion criteria provided Jul 14, 2015 RCV000435684.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
EGFR - - GRCh38
GRCh37
245 318

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
drug response
Drug-variant association: Efficacy
(Oct 27, 2015)
reviewed by expert panel
Method: curation
carboplatin, docetaxel, erlotinib, gemcitabine, and paclitaxel response - Efficacy
Drug used for Carcinoma, Non-Small-Cell Lung
Allele origin: germline
PharmGKB
Accession: SCV000268171.3
Submitted: (Jun 18, 2018)
Comment:
Drug is not necessarily used to treat response condition
Evidence details
Publications
PubMed (2)
Other databases
https://www.pharmgkb.org/clini...
Comment:
PharmGKB Level of Evidence 2A: Annotation for a variant-drug combination that qualifies for level 2B where the variant is within a VIP (Very Important Pharmacogene) ... (more)
drug response
Drug-variant association: Efficacy
(Mar 21, 2018)
reviewed by expert panel
Method: curation
gefitinib response - Efficacy
Drug used for Carcinoma, Non-Small-Cell Lung
Allele origin: germline
PharmGKB
Accession: SCV000268169.3
Submitted: (Jun 18, 2018)
Comment:
Drug is not necessarily used to treat response condition
Evidence details
Publications
PubMed (24)
Other databases
https://www.pharmgkb.org/clini...
Comment:
PharmGKB Level of Evidence 1B: Annotation for a variant-drug combination where the preponderance of evidence shows an association. The association must be replicated in more ... (more)
drug response
Drug-variant association: Efficacy
(Apr 07, 2016)
reviewed by expert panel
Method: curation
erlotinib response - Efficacy
Drug used for Carcinoma, Non-Small-Cell Lung
Allele origin: germline
PharmGKB
Accession: SCV000268170.3
Submitted: (Jun 18, 2018)
Comment:
Drug is not necessarily used to treat response condition
Evidence details
Publications
PubMed (12)
Other databases
https://www.pharmgkb.org/clini...
Comment:
PharmGKB Level of Evidence 1B: Annotation for a variant-drug combination where the preponderance of evidence shows an association. The association must be replicated in more ... (more)
drug response
Responsive
(Oct 28, 2006)
no assertion criteria provided
Method: clinical testing
Tyrosine kinase inhibitor response
Allele origin: somatic
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine
Accession: SCV000197954.1
Submitted: (Jan 26, 2015)
Evidence details
Publications
PubMed (2)
Pathogenic
(Jul 14, 2015)
no assertion criteria provided
Method: literature only
Non-small cell lung cancer
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504239.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (22)
Other databases
http://docm.genome.wustl.edu/v...
Likely pathogenic
(May 31, 2016)
no assertion criteria provided
Method: literature only
Lung adenocarcinoma
(Somatic mutation)
Allele origin: somatic
Database of Curated Mutations (DoCM)
Accession: SCV000504240.1
Submitted: (Jul 18, 2016)
Evidence details
Publications
PubMed (1)
Other databases
http://docm.genome.wustl.edu/v...
drug response
(May 19, 2005)
no assertion criteria provided
Method: literature only
NONSMALL CELL LUNG CANCER, RESPONSE TO TYROSINE KINASE INHIBITOR IN, SOMATIC
Allele origin: somatic
OMIM
Accession: SCV000038362.4
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (4)
drug response
(May 19, 2005)
no assertion criteria provided
Method: literature only
ADENOCARCINOMA OF LUNG, RESPONSE TO TYROSINE KINASE INHIBITOR IN, SOMATIC
Allele origin: somatic
OMIM
Accession: SCV000038363.4
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (4)

Citations for this variant

Title Author Journal Year Link
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity. Chang MT Nature biotechnology 2016 PMID: 26619011
Comparison of clinical outcomes of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations after tyrosine kinase inhibitors treatment: a meta-analysis. Sheng M European journal of clinical pharmacology 2016 PMID: 26490356
Prospective enterprise-level molecular genotyping of a cohort of cancer patients. MacConaill LE The Journal of molecular diagnostics : JMD 2014 PMID: 25157968
Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. Shi Y The Lancet. Oncology 2013 PMID: 23948351
Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. Sequist LV Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2013 PMID: 23816960
MEK inhibitors reverse resistance in epidermal growth factor receptor mutation lung cancer cells with acquired resistance to gefitinib. Huang MH Molecular oncology 2013 PMID: 23102728
Impact of systematic EGFR and KRAS mutation evaluation on progression-free survival and overall survival in patients with advanced non-small-cell lung cancer treated by erlotinib in a French prospective cohort (ERMETIC project--part 2). Cadranel J Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2012 PMID: 22982650
Efficacy of EGFR tyrosine kinase inhibitors for non-adenocarcinoma NSCLC patients with EGFR mutation. Cho SH Cancer chemotherapy and pharmacology 2012 PMID: 22760226
Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. Ramalingam SS Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2012 PMID: 22753918
Plasma epidermal growth factor receptor mutation analysis and possible clinical applications in pulmonary adenocarcinoma patients treated with erlotinib. Chen YM Oncology letters 2012 PMID: 22740981
Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Yang JC The Lancet. Oncology 2012 PMID: 22452895
First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. Han JY Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2012 PMID: 22370314
Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Rosell R The Lancet. Oncology 2012 PMID: 22285168
Pretreatment epidermal growth factor receptor (EGFR) T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non-small-cell lung cancer. Su KY Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2012 PMID: 22215752
Epidermal growth factor receptor mutation status in circulating free DNA in serum: from IPASS, a phase III study of gefitinib or carboplatin/paclitaxel in non-small cell lung cancer. Goto K Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2012 PMID: 21900837
Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non-small-cell lung cancer. Brugger W Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2011 PMID: 21969500
Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Zhou C The Lancet. Oncology 2011 PMID: 21783417
Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). Fukuoka M Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2011 PMID: 21670455
Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. Maemondo M The New England journal of medicine 2010 PMID: 20573926
Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non-small-cell lung cancer. Sequist LV Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2010 PMID: 20479403
Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial. Douillard JY Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2010 PMID: 20038723
Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Mitsudomi T The Lancet. Oncology 2010 PMID: 20022809
Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. Mitsudomi T The FEBS journal 2010 PMID: 19922469
In silico identification of significant detrimental missense mutations of EGFR and their effect with 4-anilinoquinazoline-based drugs. Rajasekaran R Applied biochemistry and biotechnology 2010 PMID: 19455431
Screening for epidermal growth factor receptor mutations in lung cancer. Rosell R The New England journal of medicine 2009 PMID: 19692684
Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. Mok TS The New England journal of medicine 2009 PMID: 19692680
Prognostic implication of EGFR, KRAS, and TP53 gene mutations in a large cohort of Japanese patients with surgically treated lung adenocarcinoma. Kosaka T Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2009 PMID: 19096302
Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib. Miller VA Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2008 PMID: 18349398
Prognostic and therapeutic implications of EGFR and KRAS mutations in resected lung adenocarcinoma. Marks JL Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2008 PMID: 18303429
Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in mainland China. Wu YL Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2007 PMID: 17473659
Intron 1 CA dinucleotide repeat polymorphism and mutations of epidermal growth factor receptor and gefitinib responsiveness in non-small-cell lung cancer. Han SW Pharmacogenetics and genomics 2007 PMID: 17429313
Predictive factors associated with prolonged survival in patients with advanced non-small-cell lung cancer (NSCLC) treated with gefitinib. Satouchi M British journal of cancer 2007 PMID: 17387341
Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib. Hirsch FR Annals of oncology : official journal of the European Society for Medical Oncology 2007 PMID: 17317677
Response to treatment and survival of patients with non-small cell lung cancer undergoing somatic EGFR mutation testing. Sequist LV The oncologist 2007 PMID: 17285735
The impact of epidermal growth factor receptor gene status on gefitinib-treated Japanese patients with non-small-cell lung cancer. Ichihara S International journal of cancer 2007 PMID: 17192902
Gefitinib for non-small-cell lung cancer patients with epidermal growth factor receptor gene mutations screened by peptide nucleic acid-locked nucleic acid PCR clamp. Sutani A British journal of cancer 2006 PMID: 17106442
Novel heteroduplex method using small cytology specimens with a remarkably high success rate for analysing EGFR gene mutations with a significant correlation to gefitinib efficacy in non-small-cell lung cancer. Oshita F British journal of cancer 2006 PMID: 17047654
Clinical predictors versus epidermal growth factor receptor mutation in gefitinib-treated non-small-cell lung cancer patients. Han SW Lung cancer (Amsterdam, Netherlands) 2006 PMID: 16956694
Evaluation of the epidermal growth factor receptor gene mutation and copy number in non-small cell lung cancer with gefitinib therapy. Endo K Oncology reports 2006 PMID: 16865253
Epidermal growth factor-independent transformation of Ba/F3 cells with cancer-derived epidermal growth factor receptor mutants induces gefitinib-sensitive cell cycle progression. Jiang J Cancer research 2005 PMID: 16204070
Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials. Bell DW Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2005 PMID: 16204011
Clinicopathologic significance of the mutations of the epidermal growth factor receptor gene in patients with non-small cell lung cancer. Tomizawa Y Clinical cancer research : an official journal of the American Association for Cancer Research 2005 PMID: 16203769
Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas. Taron M Clinical cancer research : an official journal of the American Association for Cancer Research 2005 PMID: 16115929
Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. Eberhard DA Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2005 PMID: 16043828
EGFR mutation and response of lung cancer to gefitinib. Toyooka S The New England journal of medicine 2005 PMID: 15901872
Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small cell lung cancer. Chou TY Clinical cancer research : an official journal of the American Association for Cancer Research 2005 PMID: 15897572
EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Pao W Proceedings of the National Academy of Sciences of the United States of America 2004 PMID: 15329413
EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Paez JG Science (New York, N.Y.) 2004 PMID: 15118125
Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. Lynch TJ The New England journal of medicine 2004 PMID: 15118073
http://docm.genome.wustl.edu/variants/ENST00000275493:c.2573T>G - - - -
https://www.pharmgkb.org/clinicalAnnotation/981420042 - - - -
https://www.pharmgkb.org/clinicalAnnotation/981475838 - - - -
https://www.pharmgkb.org/clinicalAnnotation/981475880 - - - -

Record last updated Aug 16, 2019