PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance.
ClinVar Genomic variation as it relates to human health
NM_005228.5(EGFR):c.2573T>G (p.Leu858Arg)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Drug response
Mar 2021 by
PharmGKB
Somatic
Clinical impact
Help
The aggregate somatic clinical impact for this variant for one or more tumor types, using the AMP/ASCO/CAP terminology. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(2)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate somatic clinical impact for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_005228.5(EGFR):c.2573T>G (p.Leu858Arg)
Variation ID: 16609 Accession: VCV000016609.17
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 7p11.2 7: 55191822 (GRCh38) [ NCBI UCSC ] 7: 55259515 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jan 30, 2015 Apr 20, 2024 Mar 24, 2021 Somatic - Clinical impact Feb 20, 2024 Feb 20, 2024 Feb 23, 2018 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_005228.5:c.2573T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005219.2:p.Leu858Arg missense NM_001346897.2:c.2438T>G NP_001333826.1:p.Leu813Arg missense NM_001346898.2:c.2573T>G NP_001333827.1:p.Leu858Arg missense NM_001346899.2:c.2438T>G NP_001333828.1:p.Leu813Arg missense NM_001346900.2:c.2414T>G NP_001333829.1:p.Leu805Arg missense NM_001346941.2:c.1772T>G NP_001333870.1:p.Leu591Arg missense NC_000007.14:g.55191822T>G NC_000007.13:g.55259515T>G NG_007726.3:g.177791T>G LRG_304:g.177791T>G LRG_304t1:c.2573T>G P00533:p.Leu858Arg - Protein change
- L858R, L591R, L805R, L813R
- Other names
- -
- Canonical SPDI
- NC_000007.14:55191821:T:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| EGFR | No evidence available | No evidence available |
GRCh38 GRCh37 |
2680 | 3034 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| drug response (1) |
no assertion criteria provided
|
May 19, 2005 | RCV000018084.71 | |
| drug response (1) |
no assertion criteria provided
|
May 19, 2005 | RCV000018083.97 | |
| drug response (1) |
no assertion criteria provided
|
Oct 28, 2006 | RCV000150629.12 | |
| drug response (1) |
reviewed by expert panel
|
Mar 24, 2021 | RCV000211323.12 | |
| Pathogenic (3) |
criteria provided, single submitter
|
Jun 6, 2022 | RCV000418019.12 | |
| Pathogenic (1) |
no assertion criteria provided
|
Jul 14, 2015 | RCV000435684.12 | |
| Pathogenic (1) |
criteria provided, single submitter
|
May 28, 2019 | RCV000987885.9 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
drug response
Drug-variant association: Efficacy
(Mar 24, 2021)
|
reviewed by expert panel
Method: curation
|
gefitinib response - Efficacy
Drug used for
Carcinoma, Non-Small-Cell Lung
Affected status: yes
Allele origin:
germline
|
PharmGKB
Accession: SCV000268169.4
First in ClinVar: May 22, 2016 Last updated: Dec 12, 2021
Comment:
Drug is not necessarily used to treat response condition
|
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
|
|
|
Pathogenic
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Lung cancer
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001137371.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
|
|
Pathogenic
(Jun 06, 2022)
|
criteria provided, single submitter
Method: research
|
Lung adenocarcinoma
Affected status: yes
Allele origin:
somatic
|
Liquid Biopsy and Cancer Interception Group, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research
Accession: SCV003806315.1
First in ClinVar: Mar 04, 2023 Last updated: Mar 04, 2023 |
Number of individuals with the variant: 1
|
|
|
drug response
(Oct 28, 2006)
|
no assertion criteria provided
Method: clinical testing
|
Tyrosine kinase inhibitor response
Affected status: not provided
Allele origin:
somatic
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000197954.1
First in ClinVar: Jan 30, 2015 Last updated: Jan 30, 2015 |
Number of individuals with the variant: 236
|
|
|
drug response
(May 19, 2005)
|
no assertion criteria provided
Method: literature only
|
NONSMALL CELL LUNG CANCER, RESPONSE TO TYROSINE KINASE INHIBITOR IN, SOMATIC
Affected status: not provided
Allele origin:
somatic
|
OMIM
Accession: SCV000038362.4
First in ClinVar: Apr 04, 2013 Last updated: Jan 28, 2018 |
Comment on evidence:
In tumors from 2 patients with nonsmall cell lung cancer (211980), Lynch et al. (2004) identified a 2573T-G transversion in the EGFR gene, resulting in … (more)
In tumors from 2 patients with nonsmall cell lung cancer (211980), Lynch et al. (2004) identified a 2573T-G transversion in the EGFR gene, resulting in a leu858-to-arg (L858R) substitution. In 3 lung adenocarcinomas and 3 NSCLC tumors, Paez et al. (2004) identified the L858R mutation in heterozygous state. Pao et al. (2004) identified the L858R mutation in lung cancers from 'never smokers,' which were associated with sensitivity to 2 tyrosine kinase inhibitors. The tumors were most often adenocarcinomas. They identified this mutation as being adjacent to the highly conserved DGF motif in the activation loop of the kinase. Toyooka et al. (2005) identified 2 EGFR mutations, T790M (131550.0006) and L858R, in resected tumor specimens taken from 2 women with nonsmall cell lung cancer before treatment with chemotherapy or radiation. Both patients later had recurrent disease and eventually died, suggesting that tumors with both these mutations are very aggressive. One patient was treated with gefitinib and had progression. (less)
|
|
|
drug response
(May 19, 2005)
|
no assertion criteria provided
Method: literature only
|
ADENOCARCINOMA OF LUNG, RESPONSE TO TYROSINE KINASE INHIBITOR IN, SOMATIC
Affected status: not provided
Allele origin:
somatic
|
OMIM
Accession: SCV000038363.4
First in ClinVar: Apr 04, 2013 Last updated: Jan 28, 2018 |
Comment on evidence:
In tumors from 2 patients with nonsmall cell lung cancer (211980), Lynch et al. (2004) identified a 2573T-G transversion in the EGFR gene, resulting in … (more)
In tumors from 2 patients with nonsmall cell lung cancer (211980), Lynch et al. (2004) identified a 2573T-G transversion in the EGFR gene, resulting in a leu858-to-arg (L858R) substitution. In 3 lung adenocarcinomas and 3 NSCLC tumors, Paez et al. (2004) identified the L858R mutation in heterozygous state. Pao et al. (2004) identified the L858R mutation in lung cancers from 'never smokers,' which were associated with sensitivity to 2 tyrosine kinase inhibitors. The tumors were most often adenocarcinomas. They identified this mutation as being adjacent to the highly conserved DGF motif in the activation loop of the kinase. Toyooka et al. (2005) identified 2 EGFR mutations, T790M (131550.0006) and L858R, in resected tumor specimens taken from 2 women with nonsmall cell lung cancer before treatment with chemotherapy or radiation. Both patients later had recurrent disease and eventually died, suggesting that tumors with both these mutations are very aggressive. One patient was treated with gefitinib and had progression. (less)
|
|
|
Pathogenic
(Jul 14, 2015)
|
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: SCV000504239.1
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: SCV000504240.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
|
Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Adenocarcinoma of lung
Affected status: yes
Allele origin:
somatic
|
Key Laboratory of Carcinogenesis and Cancer Invasion, Central South University
Accession: SCV004042724.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
|
Comment:
Comment:
L858R is among the most common sensitizing EGFR mutations in NSCLC, and is assessed via DNA mutational analysis including Sanger sequencing and next generation sequencing methods. Tyrosine kinase inhibitor erlotinib is associated with improved progression free survival over chemotherapy in EGFR L858R patients (civic.EID:885).
Comment:
L858R is among the most common sensitizing EGFR mutations in NSCLC, and is assessed via DNA mutational analysis, including Sanger sequencing and next generation sequencing methods. Tyrosine kinase inhibitor afatinib is FDA approved as a first line systemic therapy in NSCLC with sensitizing EGFR mutation (civic.EID:2997).
Germline Functional Evidence
| 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. |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance.
Comment:
L858R is among the most common sensitizing EGFR mutations in NSCLC, and is assessed via DNA mutational analysis including Sanger sequencing and next generation sequencing methods. Tyrosine kinase inhibitor erlotinib is associated with improved progression free survival over chemotherapy in EGFR L858R patients (civic.EID:885).
Comment:
L858R is among the most common sensitizing EGFR mutations in NSCLC, and is assessed via DNA mutational analysis, including Sanger sequencing and next generation sequencing methods. Tyrosine kinase inhibitor afatinib is FDA approved as a first line systemic therapy in NSCLC with sensitizing EGFR mutation (civic.EID:2997).
Citations for germline classification of 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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/variant/PA166157527 | - | - | - | - |
| click to load more click to collapse | ||||
Conditions - Somatic
| Tumor type
Help
The tumor type for this variant-condition (RCV) record in ClinVar. |
Clinical impact (# of submissions)
Help
The aggregate somatic clinical impact for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate somatic clinical impact is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status. |
Oncogenicity
Help
The aggregate oncogenicity classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate oncogenicity classification is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the tumor type. |
Variation/condition record
Help
The most recent date that a submitter evaluated this variant for the tumor type. |
|---|---|---|---|---|
|
Tier I (Strong)
- therapeutic
- sensitivity/response
(2)
|
Feb 23, 2018 | RCV000435684.12 |
Submissions - Somatic
|
Clinical impact
Help
The submitted somatic clinical impact for each SCV record. (Last evaluated) |
Review Status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Tumor type
Help
The tumor type for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the somatic clinical impact, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|---|
|
Tier I (Strong)
- Therapeutic
-
sensitivity/response - Erlotinib (Feb 23, 2018)
|
criteria provided, single submitter
Method: curation
|
Non-small cell lung carcinoma
Affected status: unknown
Allele origin:
somatic
|
CIViC knowledgebase, Washington University School of Medicine
Accession: SCV004565358.1
First In ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
L858R is among the most common sensitizing EGFR mutations in NSCLC, and is assessed via DNA mutational analysis including Sanger sequencing and next generation sequencing … (more)
L858R is among the most common sensitizing EGFR mutations in NSCLC, and is assessed via DNA mutational analysis including Sanger sequencing and next generation sequencing methods. Tyrosine kinase inhibitor erlotinib is associated with improved progression free survival over chemotherapy in EGFR L858R patients (civic.EID:885). (less)
|
|
|
Tier I (Strong)
- Therapeutic
-
sensitivity/response - Afatinib (Feb 22, 2018)
|
criteria provided, single submitter
Method: curation
|
Non-small cell lung carcinoma
Affected status: unknown
Allele origin:
somatic
|
CIViC knowledgebase, Washington University School of Medicine
Accession: SCV004565359.1
First In ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
L858R is among the most common sensitizing EGFR mutations in NSCLC, and is assessed via DNA mutational analysis, including Sanger sequencing and next generation sequencing … (more)
L858R is among the most common sensitizing EGFR mutations in NSCLC, and is assessed via DNA mutational analysis, including Sanger sequencing and next generation sequencing methods. Tyrosine kinase inhibitor afatinib is FDA approved as a first line systemic therapy in NSCLC with sensitizing EGFR mutation (civic.EID:2997). (less)
|
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance.
Comment:
L858R is among the most common sensitizing EGFR mutations in NSCLC, and is assessed via DNA mutational analysis including Sanger sequencing and next generation sequencing methods. Tyrosine kinase inhibitor erlotinib is associated with improved progression free survival over chemotherapy in EGFR L858R patients (civic.EID:885).
Comment:
L858R is among the most common sensitizing EGFR mutations in NSCLC, and is assessed via DNA mutational analysis, including Sanger sequencing and next generation sequencing methods. Tyrosine kinase inhibitor afatinib is FDA approved as a first line systemic therapy in NSCLC with sensitizing EGFR mutation (civic.EID:2997).
Citations for somatic classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| EGFR Fusions as Novel Therapeutic Targets in Lung Cancer. | Konduri K | Cancer discovery | 2016 | PMID: 27102076 |
| Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT). | De Grève J | PloS one | 2016 | PMID: 27032107 |
| In vitro modeling to determine mutation specificity of EGFR tyrosine kinase inhibitors against clinically relevant EGFR mutants in non-small-cell lung cancer. | Hirano T | Oncotarget | 2015 | PMID: 26515464 |
| U.S. Food and Drug Administration approval summary: Erlotinib for the first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations. | Khozin S | The oncologist | 2014 | PMID: 24868098 |
| Comparison of clinical outcomes following gefitinib and erlotinib treatment in non-small-cell lung cancer patients harboring an epidermal growth factor receptor mutation in either exon 19 or 21. | Lim SH | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer | 2014 | PMID: 24736073 |
| Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. | Wu YL | The Lancet. Oncology | 2014 | PMID: 24439929 |
| Afatinib: first global approval. | Dungo RT | Drugs | 2013 | PMID: 23982599 |
| 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 |
| 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 |
| 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 |
| Characterization of epidermal growth factor receptor mutations in non-small-cell lung cancer patients of African-American ancestry. | Harada T | Oncogene | 2011 | PMID: 21132006 |
| Functional analysis of epidermal growth factor receptor (EGFR) mutations and potential implications for EGFR targeted therapy. | Kancha RK | Clinical cancer research : an official journal of the American Association for Cancer Research | 2009 | PMID: 19147750 |
| BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. | Li D | Oncogene | 2008 | PMID: 18408761 |
| Functional analysis of cancer-associated EGFR mutants using a cellular assay with YFP-tagged EGFR intracellular domain. | de Gunst MM | Molecular cancer | 2007 | PMID: 17877814 |
| https://civicdb.org/links/evidence/229 | - | - | - | - |
| https://civicdb.org/links/evidence/2629 | - | - | - | - |
| https://civicdb.org/links/evidence/2994 | - | - | - | - |
| https://civicdb.org/links/evidence/2997 | - | - | - | - |
| https://civicdb.org/links/evidence/3811 | - | - | - | - |
| https://civicdb.org/links/evidence/4265 | - | - | - | - |
| https://civicdb.org/links/evidence/4285 | - | - | - | - |
| https://civicdb.org/links/evidence/4290 | - | - | - | - |
| https://civicdb.org/links/evidence/4291 | - | - | - | - |
| https://civicdb.org/links/evidence/82 | - | - | - | - |
| https://civicdb.org/links/evidence/879 | - | - | - | - |
| https://civicdb.org/links/evidence/883 | - | - | - | - |
| https://civicdb.org/links/evidence/885 | - | - | - | - |
| https://civicdb.org/links/evidence/968 | - | - | - | - |
| https://identifiers.org/civic.mpid:33 | - | - | - | - |
| click to load more click to collapse | ||||
Text-mined citations for rs121434568 ...
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 Nov 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.