Table 2.

ITAC’s potentially actionable mutations. CNG = copy number gain.

Gene	Findings	References	Types of Alterations	Variant Classification of Alterations	Target Drugs (Approved at Least by One Regulatory Agency in Other Cancer Settings)	Principal Treatment Indication (Tumors for Which Are Approved)
MET	0–64% (46/72)	Projetti et al. 2015. [48]	20 CNG	Amplification	Capmatinib	NSCLC
			(S156L)	(Missense)	(No drugs)
EGFR	2–63% (27/43)	Szablewski et al., 2013 [54]	5 CNG	Amplification	Afatinib	NSCLC
PIK3CA	10–22% (5/48; 11/50)	Sánchez-Fernández et al., 2021 [5]; Riobello et al., 2021 [53]	Q546R, H1047R, K111E	Missense	Alpelisib	Breast cancer
			(D939G), (E726K), (V1534M), (D454G)	(Missense)	(No drugs)
NRAS	8% (4/48)	Sánchez-Fernández et al., 2021 [5]	G12T	Missense	Bimetinib	Melanoma
			(6-10CNG)	(Amplification)	(No drugs)
BRCA 1 and BRCA 2	8–14% (4/48) (7/50)	Sánchez-Fernández et al., 2021 [5]. Riobello et al., 2021 [53]	R1347G	Missense	Olaparib, talazoparib, niraparib	Breast cancer, ovarian cancer, prostatic cancer
			L3326*, K3226*	Nonsense
			5 CNG	Amplification
			(P1603Rfs*13), (Q1111Nfs*5)	(Frameshift)	(No drugs)
			(V1534M)	(Missense)	(No drugs)
ATM	8–16% (4/48) (8/50)	Sánchez-Fernández et al., 2021 [5]. Riobello et al., 2021 [53]	Q684P, P1054R, D1853V, V410A	Missense	Olaparib	Prostatic cancer
AR	0–20% (10/50)	Riobello et al., 2021 [53]	Q79–Q80 dupl.,	Inframe duplication	Bicalutamide, leuprolina	Salivary glands cancer
			(Q77–Q80 del.), (Q79–Q80 del.,)	(Deletion)	(No drugs)
ERBB2	0–6% (3/50)	Riobello et al., 2021 [53]	S310F	Missense	Trastuzumab, Pertuzumab, Ado-trastuzumab emtansine, Fam-trastuzumab deruxtecan, Margetuximab, Neratinib, Lapatinib	Breast cancer, Gastric cancer
BRAF	0–6% (1/18)	Franchi et al., 2014 [40]	V600E	Missense	Dabrafenib, cobimetinib +MEK inhibitors	Melanoma
			(D594N)	(Missense)	(No drugs)
IDH1	sporadic	Riobello et al., 2021 [53]	R132C	Missense	Ivosidenib	Ductal bile carcinoma