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EGFR
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EGFR V774M
GeneEGFR
Variantmissense
Amino Acid ChangeV774M
Transcript ID (GRCh37/hg19)ENST00000275493
Codon774
Exon20
Germline/Somatic?Somatic
Pertinent Negative In
Tumor TypePrimary Site
See All Pertinent Negatives

Interpretations

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Tier 2
EGFR
Variants
EGFR V774M
Primary Sites
Brain
Tumor Types
Glioblastoma
Interpretation

EGFR mutations have been reported in up to 21% of glioblastoma tumors (GBM). In GBM, EGFR mutations typically cluster in the extracellular domain and include in-frame deletions and missense mutations. However, mutations (such as V774M) in the tyrosine kinase domain of EGFR have been previously reported in GBM. The clinical significance of this mutation with regards to response to TKI therapy in GBM needs further elucidation. Results should be interpreted in conjunction with other laboratory and clinical findings.

Last updated: 2017-02-03 21:49:47 UTC
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Tier 1
EGFR
Variants
EGFR H773L
EGFR V774M
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

EGFR exon 20 insertion testing identifies a distinct subset of lung adenocarcinomas, accounting for at least 9% of all EGFR-mutated cases and by molecular modeling, are predicted to have potentially different effects on erlotinib binding. Studies show that in contrast to the more classic activating EGFR mutations, these insertions have been associated with de novo resistance to approved EGFR-TKIs (erlotinib and gefitinib). In a recent study, patients with advanced lung adenocarcinoma harboring exon 20 insertions demonstrated no response or partial response following treatment with TK inhibitors. This rare complex mutation (p.H773_V774delinsLM) results in the H773L/V774 mutation compound at the same allele, potentially weakening the inactive state and leading to constitutional activation of EGFR. A recent clinical report suggests this mutation is insensitive to the reversible TKI gefitinib, but can be suppressed by the irreversible TKI osimertinib, leading to sustained disease control (Yang et al., Lung Cancer, 121:1-4, 2018). Exon 20 insertion mutations in EGFR may be associated with clinical trials (https://clinicaltrials.gov/).

Last updated: 2019-01-22 18:50:26 UTC
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Disclaimer: You assume full responsibility for all risks associated with using this PMKB website. The Englander Institute for Precision Medicine at Weill Cornell Medicine makes no guarantee of the comprehensiveness, reliability or accuracy of the information on this website and assumes no responsibility for errors in the information associated with this web site. Healthcare providers and patients must integrate all clinical and laboratory findings as well as information from a variety of sources before deciding on appropriate clinical care options.


When using PMKB, please cite: Huang et al., JAMIA 2017


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