TABLE 12.

ECFR Mutations Accounting Individually for at Least 1% of All EGFR Mutations

EGFR Exon	EGFR Codon	Mutationsa (Amino Acid)	Nucleotide Substitutions	Approximate % of All EGFR Mutations
18	E709	E709K	c.2125G>A	1
		E709A	c.2126A>C
		E709G	c.2126A>G
		E709V	c.2126A>T
		E709D	c.2127A>C, c.2127A>T
		E709Q	c.2125G>C
	G719	G719S	c.2155G>A	2–5
		G719A	c.2156G>C
		G719C	c.2155G>T
		G719D	c.2156G>A
19	K739	Insertions		1
	1740	18-bp ins
	P741
	V742
	A743
	1744
	E746	Deletions		45
	L747	15-bp del
	R748	18-bp del
	E749	9-bp del
	A750	24-bp del
	T751	12-bp del
	S752
	P753
20	S768	Insertions		4–10
	V769
	D770
	N771
	P772
	H773
	V774
	S768	S768I	c.2303G T	1 2
	T790	T790M	C.2369>T	2b
21	L858	L858R	c.2573T>G	40
		L858M	c.2572>A (rare)
	L861	L861Q	c.2582T>A	2–5
		L861R	c.2582T>G

Abbreviations: del, deletion; ins, insertion.

^aExplanatory note.

^bExplanatory note.

Notes and footnotes: All mutations listed are generally associated with sensitivity to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) except T790M and exon 20 insertions. G719 and L861 mutations are considered sensitive but somewhat less so than the major exon 19 and 21 mutations. Because exon 20 insertions appear largely insensitive to erlotinib and gefitinib and do not coexist with other mutations, it may be acceptable to exclude them from a testing panel at this time. However, exon 20 insertions are variable in exact position and structure, and response data remain very limited for some types of insertions; therefore, some oncologists may recommend a trial of a first- or second-generation EGFR TKI. Mutations at E709 and S768 usually occur in combination with another of the listed. Data derived from Chen et al¹¹⁰; He et al¹⁶⁶; Oxnard et al²¹⁰; Wu et al²⁷⁸; Bamford et al³¹¹; De Pas et al³¹²; and Murray et al.³¹³