ClinVar Genomic variation as it relates to human health
NM_005228.5(EGFR):c.2303G>T (p.Ser768Ile)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_005228.5(EGFR):c.2303G>T (p.Ser768Ile)
Variation ID: 45251 Accession: VCV000045251.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7p11.2 7: 55181312 (GRCh38) [ NCBI UCSC ] 7: 55249005 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 May 11, 2022 Mar 11, 2011 - HGVS
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Nucleotide Protein Molecular
consequenceNM_005228.5:c.2303G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005219.2:p.Ser768Ile missense NM_001346897.2:c.2168G>T NP_001333826.1:p.Ser723Ile missense NM_001346898.2:c.2303G>T NP_001333827.1:p.Ser768Ile missense NM_001346899.2:c.2168G>T NP_001333828.1:p.Ser723Ile missense NM_001346900.2:c.2144G>T NP_001333829.1:p.Ser715Ile missense NM_001346941.2:c.1502G>T NP_001333870.1:p.Ser501Ile missense NR_047551.1:n.1259C>A non-coding transcript variant NC_000007.14:g.55181312G>T NC_000007.13:g.55249005G>T NG_007726.3:g.167281G>T LRG_304:g.167281G>T LRG_304t1:c.2303G>T P00533:p.Ser768Ile - Protein change
- S768I, S723I, S715I, S501I
- Other names
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- Canonical SPDI
- NC_000007.14:55181311:G:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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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. |
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EGFR | No evidence available | No evidence available |
GRCh38 GRCh37 |
2657 | 3006 | |
EGFR-AS1 | - | - | - | GRCh38 | - | 200 |
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
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (3) |
criteria provided, single submitter
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Mar 11, 2011 | RCV000038407.9 | |
Likely pathogenic (1) |
no assertion criteria provided
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Dec 26, 2014 | RCV000435248.2 | |
Likely pathogenic (1) |
no assertion criteria provided
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Jul 14, 2015 | RCV000428042.2 |
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
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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. |
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Pathogenic
(Mar 11, 2011)
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criteria provided, single submitter
Method: clinical testing
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Non-Small Cell Lung Cancer
Affected status: not provided
Allele origin:
somatic
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000062079.3
First in ClinVar: May 03, 2013 Last updated: Jan 31, 2015 |
Number of individuals with the variant: 17
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Likely pathogenic
(Jul 14, 2015)
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no assertion criteria provided
Method: literature only
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Carcinoma of esophagus
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000505072.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(Jul 14, 2015)
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no assertion criteria provided
Method: literature only
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Non-small cell lung carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000505071.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Likely pathogenic
(Dec 26, 2014)
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no assertion criteria provided
Method: literature only
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Squamous cell lung carcinoma
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000505073.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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Pathogenic
(-)
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no assertion criteria provided
Method: curation
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Non-small cell lung carcinoma
Affected status: yes
Allele origin:
germline
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Molecular Diagnostics Laboratory, University of Rochester Medical Center
Accession: SCV002506984.1
First in ClinVar: May 11, 2022 Last updated: May 11, 2022 |
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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
HelpTitle | Author | Journal | Year | Link |
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A method of high-throughput functional evaluation of EGFR gene variants of unknown significance in cancer. | Kohsaka S | Science translational medicine | 2017 | PMID: 29141884 |
Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. | Yang JC | The Lancet. Oncology | 2015 | PMID: 26051236 |
Clinical and in vivo evidence that EGFR S768I mutant lung adenocarcinomas are sensitive to erlotinib. | Hellmann MD | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer | 2014 | PMID: 25521405 |
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 |
Good clinical response to gefitinib in a non-small cell lung cancer patient harboring a rare somatic epidermal growth factor gene point mutation; codon 768 AGC > ATC in exon 20 (S768I). | Masago K | Japanese journal of clinical oncology | 2010 | PMID: 20522446 |
Second-line treatments after first-line gefitinib therapy in advanced nonsmall cell lung cancer. | Wu JY | International journal of cancer | 2010 | PMID: 19536777 |
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 |
EGFR mutants found in non-small cell lung cancer show different levels of sensitivity to suppression of Src: implications in targeting therapy. | Fu YN | Oncogene | 2008 | PMID: 17653080 |
EGFR point mutation in non-small cell lung cancer is occasionally accompanied by a second mutation or amplification. | Yokoyama T | Cancer science | 2006 | PMID: 16863509 |
Gefitinib-sensitizing mutations in esophageal carcinoma. | Guo M | The New England journal of medicine | 2006 | PMID: 16707764 |
Distinctive activation patterns in constitutively active and gefitinib-sensitive EGFR mutants. | Chen YR | Oncogene | 2006 | PMID: 16205628 |
High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan. | Huang SF | Clinical cancer research : an official journal of the American Association for Cancer Research | 2004 | PMID: 15623594 |
http://docm.genome.wustl.edu/variants/ENST00000275493:c.2303G>T | - | - | - | - |
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Text-mined citations for rs121913465 ...
HelpRecord last updated May 12, 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.