VCV000016611.5 - ClinVar

NM_005228.5(EGFR):c.2155G>T (p.Gly719Cys)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(5)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification 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.

Pathogenic/Likely pathogenic; drug response

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_005228.5(EGFR):c.2155G>T (p.Gly719Cys)

Variation ID: 16611 Accession: VCV000016611.5

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7p11.2 7: 55174014 (GRCh38) [ NCBI UCSC ] 7: 55241707 (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 31, 2015	Mar 8, 2017	May 31, 2016

HGVS

Nucleotide	Protein	Molecular consequence
NM_005228.5:c.2155G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005219.2:p.Gly719Cys	missense
NM_001346897.2:c.2020G>T	NP_001333826.1:p.Gly674Cys	missense
NM_001346898.2:c.2155G>T	NP_001333827.1:p.Gly719Cys	missense
NM_001346899.2:c.2020G>T	NP_001333828.1:p.Gly674Cys	missense
NM_001346900.2:c.1996G>T	NP_001333829.1:p.Gly666Cys	missense
NM_001346941.2:c.1354G>T	NP_001333870.1:p.Gly452Cys	missense
NC_000007.14:g.55174014G>T
NC_000007.13:g.55241707G>T
NG_007726.3:g.159983G>T
LRG_304:g.159983G>T
LRG_304t1:c.2155G>T
	P00533:p.Gly719Cys

... more HGVS ... less HGVS

Protein change

G719C, G452C, G674C, G666C

Other names

EGFR, GLY719CYS (rs28929495)

Canonical SPDI

NC_000007.14:55174013:G:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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

ClinGen: CA126719 UniProtKB: P00533#VAR_026087 OMIM: 131550.0004 dbSNP: rs28929495 VarSome

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
Gene	OMIM	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	2678	3032

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.
Nonsmall cell lung cancer, response to tyrosine kinase inhibitor in, somatic	drug response (1)	no assertion criteria provided	May 20, 2004	RCV000018086.85
Non-small cell lung carcinoma	Pathogenic (2)	no assertion criteria provided	Jul 14, 2015	RCV000038380.6
Glioblastoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000426731.1
Lung adenocarcinoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000433465.1

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.
Pathogenic (Nov 23, 2009)	no assertion criteria provided Method: clinical testing	Non-Small Cell Lung Cancer Affected status: not provided Allele origin: somatic	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000062052.2 First in ClinVar: May 03, 2013 Last updated: Jan 31, 2015	Publications: PubMed (3) PubMed: 15118073‚ 19536777‚ 21841502 Number of individuals with the variant: 14
drug response (May 20, 2004)	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: SCV000038365.2 First in ClinVar: Apr 04, 2013 Last updated: Feb 02, 2017	Publications: PubMed (1) PubMed: 15118073 Comment on evidence: In a tumor from a patient with nonsmall cell lung cancer (211980) responsive to gefitinib, Lynch et al. (2004) identified a somatic 2155G-T transversion in … (more) In a tumor from a patient with nonsmall cell lung cancer (211980) responsive to gefitinib, Lynch et al. (2004) identified a somatic 2155G-T transversion in the EGFR gene, resulting in a gly719-to-cys (G719C) mutation. (less)
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: SCV000504232.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000275493:c.2155G>T
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: SCV000504233.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000275493:c.2155G>T
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: SCV000504231.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (13) PubMed: 15118073‚ 19922469‚ 15710947‚ 20479403‚ 19671738‚ 15329413‚ 18199554‚ 22753918‚ 16011858‚ 15118125‚ 16115929‚ 25157968‚ 23102728 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000275493:c.2155G>T

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.

Citations for germline classification of 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
Prospective enterprise-level molecular genotyping of a cohort of cancer patients.	MacConaill LE	The Journal of molecular diagnostics : JMD	2014	PMID: 25157968
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
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
Activity of epidermal growth factor receptor-tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring rare epidermal growth factor receptor mutations.	De Pas T	Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer	2011	PMID: 21841502
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
Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer.	Mitsudomi T	The FEBS journal	2010	PMID: 19922469
Second-line treatments after first-line gefitinib therapy in advanced nonsmall cell lung cancer.	Wu JY	International journal of cancer	2010	PMID: 19536777
Double EGFR mutants containing rare EGFR mutant types show reduced in vitro response to gefitinib compared with common activating missense mutations.	Tam IY	Molecular cancer therapeutics	2009	PMID: 19671738
Impact of common epidermal growth factor receptor and HER2 variants on receptor activity and inhibition by lapatinib.	Gilmer TM	Cancer research	2008	PMID: 18199554
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 tyrosine kinase domain of the EGFR gene associated with gefitinib response in non-small-cell lung cancer.	Rosell R	Lung cancer (Amsterdam, Netherlands)	2005	PMID: 16011858
Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib.	Han SW	Journal of clinical oncology : official journal of the American Society of Clinical Oncology	2005	PMID: 15710947
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.2155G>T	-	-	-	-
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Text-mined citations for rs28929495 ...

These 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 May 01, 2024

ClinVar Genomic variation as it relates to human health

NM_005228.5(EGFR):c.2155G>T (p.Gly719Cys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs28929495 ...