EGFR L858R

Variant type

missense mutation

Location

Chromosome 7

Exon

21

Protein change

p.L858R

cDNA change

-

Genomic coordinate

Chromosome 7

FATHMM prediction

-

Variant category

I

Variant description

The L858R mutation results in an amino acid substitution at position 858 of EGFR, from a leucine (L) to an arginine (R). This mutation occurs within exon 21, which encodes part of the kinase domain, and occurs with a frequency of approximately 43% in E​GFR mutant lung tumors (PMID: 20022809). The mutation increase the kinase activity of EGFR, leading to hyperactivation of downstream pro-survival signaling pathways (PMID: 15284455). Multiple EGFR tyrosine kinase inhibitors (TKIs) have been developed or are in development. In the metastatic setting, EGFR mutations are strong predictors of efficacy for the EGFR tyrosine kinase inhibitors (TKIs), including the "first-generation" drugs erlotinib (Tarceva) and gefitinib (Iressa) and the "second-generation" drug, afatinib (Gilotrif).

Variant frequence

This section displays the distribution of mutated samples and tissue types (top 5).

Accoiciated drug