EGFR C797S resistance mutation

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`BIO-EGFR-C797S`
Type	Biomarker
Aliases	EGFR C797S — мутація резистентностіEGFR exon 20 C797SEGFR p.C797S
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	None declared
Sources	`SRC-ESMO-NSCLC-METASTATIC-2024` `SRC-MARIPOSA2-PASSARO-2024` `SRC-NCCN-NSCLC-2025`

Biomarker Facts

Biomarker type	gene_mutation
Mutation details	{"exon": "20", "functional_impact": "acquired resistance to 3rd-generation EGFR-TKI (osimertinib); covalent-binding cysteine residue lost", "gene": "EGFR", "hgvs_coding": "c.2390G>C", "hgvs_protein": "p.C797S", "variant_type": "missense"}
Measurement	MethodctDNA NGS (preferred for re-biopsy at osimertinib progression) OR repeat tumor biopsy NGS Unitscategorical (positive \| negative); VAF % when available Sensitivity requirementVAF ≥1% (cfDNA) or any (tissue); cis vs trans T790M+C797S configuration must be reported when both present
Actionability lookup	{"gene": "EGFR", "variant": "C797S"}
Related biomarkers	`BIO-EGFR-T790M` `BIO-EGFR-EXON19-DELETION` `BIO-EGFR-L858R` `BIO-EGFR-MUTATION`

Notes

Acquired resistance mutation to 3rd-generation EGFR-TKI (osimertinib) — the C797 cysteine is the covalent-binding residue for osimertinib, so C797S abolishes irreversible inhibition. Most common osimertinib- resistance EGFR-on-target alteration (~7-22% of post-osimertinib re-biopsies). Triggers ESCAT IB pathway: amivantamab + lazertinib per MARIPOSA-2 (Passaro 2024). Cis vs trans T790M+C797S configuration matters: trans (different alleles) may respond to combo of 3rd-gen + 1st/2nd-gen EGFR-TKI; cis (same allele) is fully resistant to all current EGFR-TKI monotherapy and requires bypass strategy (amivantamab-based, chemo, or trial enrollment).

Used By

Red flag

RF-NSCLC-EGFR-C797S-RESISTANCE - EGFR C797S — covalent-binding-site mutation that confers acquired resistance to osimertin...