What you carry at this position in your DNA and what research says about it.
EGFR Inhibitor Response: 8/10 evidence, 30 publications.
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Sample genotype (not yours): T/T
Typical EGFR Inhibitor Response
The typical reference genotype indicates the absence of the inherited L858R mutation. If lung cancer were to develop, tumor-specific testing would determine if this mutation was acquired somatically.
What this genotype means: Typical response to EGFR inhibitors; No inherited L858R mutation.
Sample genotype (not yours): G/G
Enhanced Response to EGFR Inhibitors
Presence of the L858R mutation is indicated by carrying two copies of the G allele. In a tumor context, this mutation significantly increases sensitivity to targeted therapies like gefitinib and erlotinib.
What this genotype means: Highly sensitive to gefitinib and erlotinib; Altered EGFR kinase activity.
Sample genotype (not yours): T/G
Presence of the L858R mutation is indicated by carrying one copy of the G allele. In a tumor context, this mutation significantly increases sensitivity to targeted therapies like gefitinib and erlotinib.
Gene function and biological role
Gene Function: The EGFR gene encodes the epidermal growth factor receptor, a cell surface protein that binds to extracellular ligands to initiate cell signaling pathways [1]. These pathways regulate essential cellular processes including growth, proliferation, survival, and differentiation [2]. Under normal conditions, the receptor is tightly regulated and only active when bound to its ligand [3]. However, mutations in this gene can lead to constitutive, ligand-independent activation of the receptor, driving uncontrolled cell division and tumor formation [4].
Variant Impact: The rs121434568 variant, commonly known as L858R, is a missense mutation located in exon 21 of the EGFR gene [1]. This nucleotide substitution changes the codon from leucine to arginine at position 858, which lies within the activation loop of the tyrosine kinase domain [2]. The substitution destabilizes the inactive conformation of the kinase, keeping the receptor in a continuously active state [3]. In clinical oncology, this is one of the most common somatic driver mutations in non-small cell lung cancer, particularly in adenocarcinomas from never-smokers [4].
Key Insight: Although this mutation drives cancer growth, it also acts as an Achilles' heel, making the tumor highly sensitive to targeted therapies.
Location: EGFR. Chromosome 7 · 7p11.2 · 55.2 Mb
Estimated prevalence by population
No frequency data available
This variant is not present in the gnomAD database.
Showing effects for T/T genotype
Pharmacogenomics
Chemotherapy Response
Gefitinib Response. Evidence: 8/10. Source: PMID 15118073. Typical Response.
Erlotinib Response. Evidence: 6/10. Source: PMID 16043828. Typical Response.
Showing effects for G/G genotype
Gefitinib Response. Evidence: 8/10. Source: PMID 15118073. Increased Sensitivity.
Erlotinib Response. Evidence: 6/10. Source: PMID 16043828. Increased Sensitivity.
Showing effects for T/G genotype
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Wild-type EGFR sequence is represented by the T/T genotype, which encodes leucine at position 858 [1]. This is the standard genotype found in almost 100% of the global population. Inheriting the T allele from both parents means there is no germline predisposition related to this specific variant. In the clinical management of non-small cell lung cancer, tumors are routinely sequenced to see if they have acquired the L858R mutation somatically [2]. Lacking this mutation typically predicts a standard, lower response rate to first-generation EGFR tyrosine kinase inhibitors like gefitinib or erlotinib compared to mutation-positive tumors [3]. Instead, standard chemotherapy or other targeted agents are often preferred for these patients [4].
Typical response to EGFR inhibitors; No inherited L858R mutation.
Sample genotype: GG (Homozygous)
Arginine is encoded at position 858 in the G/G genotype [1]. This genotype is virtually non-existent in germline populations but is highly relevant when detected in lung tumor biopsies. The L858R mutation causes the EGFR kinase domain to remain in an active state, driving tumor growth while simultaneously making it vulnerable to targeted drugs [2]. Patients whose tumors harbor this mutation show remarkable clinical responses and increased survival when treated with erlotinib or gefitinib [3].
Highly sensitive to gefitinib and erlotinib; Altered EGFR kinase activity.
Sample genotype: TG (Heterozygous)
Arginine instead of leucine is encoded at position 858 in the T/G genotype [1]. While this mutation is highly famous as a somatic driver in lung cancer tumors, inheriting it in the germline is extraordinarily rare. When present in lung adenocarcinoma cells, this activating mutation hyper-sensitizes the tumor to EGFR tyrosine kinase inhibitors [2]. Clinical trials have shown that patients with L858R-positive tumors experience significantly longer progression-free survival when treated with gefitinib or erlotinib compared to standard chemotherapy [3]. Because this is typically a tumor-acquired mutation, finding it in a germline test is unusual [4].
Variants with shared genetic architecture
rs121434569 · EGFR Gene · Chr 7 · Somatic Cancer Gene
rs2227983 · EGFR Gene · Chr 7 · EGFR Therapy Response
rs2293347 · EGFR Gene · Chr 7 · Gefitinib Response
EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.
EGFR mutation and response of lung cancer to gefitinib.
Screening for epidermal growth factor receptor mutations in lung cancer.
Content updated August 2026.
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