Reported Not reported 20668451 18948947 17344846 21720365 19718025 19718025 19718025 19718025 19718025 21499247 21097718 stomach skin skin skin melanoma melanoma melanoma carcinoma skin melanoma skin melanoma skin melanoma ovary carcinoma ovary carcinoma TyrKc Ephrin_lbd TyrKc FN3 TyrKc Ephrin_lbd TyrKc Ephrin_lbd TyrKc lung carcinoma lung carcinoma TyrKc Between FN3 and TyrKc domains lung carcinoma Ephrin binding lung carcinoma FN3 lung carcinoma lung 18325633 carcinoma Ephrin_lbd Between Ephrin_lbd and GCC2_GCC3 domains lung carcinoma Ephrin_lbd 0.06 0.27 0.25 0.55 0.03 0.00 0.32 0.00 0.01 0.00 1.00 0.00 0.05 0.44 0.76 0.06 lung carcinoma Ephrin_lbd 0.01 lung carcinoma 12926553 Between and Tyrkc and SAM domains not known large intestine carcinoma TyrKc 0.01 large intestine carcinoma Between TyrKc and SAM domains 0.22 large intestine carcinoma Between TyrKc and SAM domains 0.42 large intestine carcinoma Between GCC2_GCC3 and FN3 domains 0.00 large intestine carcinoma Between FN3 and TyrKc domains 0.22 central nervous system glioma Ephrin_lbd 0.42 central nervous system glioma TyrKc 0.04 central nervous system glioma TyrKc 0.00 PolyPhenCDS Mutation Pubmed IdPrimary TissueHistologyDomainsFunctional AN 3199 predictionp.A685Tc.2053G.Aprobably damaging with a score of 1.000 possibly damaging with a score of 0.671 probably damaging with a score of 0.971 probably damaging with a score of 0.983 probably damaging with a score of 0.999 benign with a score of 0.000 probably damaging with a score of 0.998 benign with a score of 0.004 not known probably damaging with a score of 0.999 probably damaging with a score of 0.999 probably damaging with a score of 0.999 possibly damaging with a score of 0.279 probably damaging with a score of 0.989 probably damaging with a score of 1.000 probably damaging with a score of 1.000 probably damaging with a score of 0.993 probably damaging with a score of 1.000 
probably damaging with a score of 0.996 probably damaging with a score of 0.989 benign with a score of 0.000 possibly damaging with a score of 0.662 possibly damaging with a score of 0.881 probably damaging with a score of 0.993 benign with a score of 0.034 probably damaging with a score of 0.p.E860Kc.2578G.Ap.G106Dc.317G.Ap.A588Pc.1762G.Cp.D345Nc.1033G.Ap.D915Gc.2744A.Gp.G914V2741 G.Tp.R704Qc.2111G.Ap.915_917delc.2745del (CCCAGGGGA)p.A203Dc.608C.Ap.A85Tc.253G.Ap.K139Nc.417G.Tp.L269Mc.805C.Ap.Q498Hc.1494G/Cp.R52Cc.154C/Tp.P728Hc.2183C.Ap.R648Lc.1943G.Tp.P728Sc.2182C.Tp.L21Fc.63G.Tp.R704Wc.2110C.Tp.G404Sc.1210G.Ap.A688Gc.2063C.Gp.S152Fc.455C.Tp.R679Qc.2036G.Ap.S131Fc.392C.Tp.Q756Rc.2267A.GIdentification of EPHB6 MutationNote: The table contains data from the databases of http://www.sanger.ac.uk/genetics/CGP/cosmic/, http://strubiol.icr.ac.uk/extra/mokca, and the references were listed in the column of “Pubmed Id”. The NSCLC mutations identified in this study were marked as “not reported”. Two sequence homology-based tools were used to predict the potential impact of the identified non-synonymous substitutions on protein function: Sort Intolerant from Tolerant (SIFT; http://sift.bii.a-star.edu.sg/) and Polymorphism Phenotype (PolyPhen-2; http://MedChemExpress JW 74 genetics.bwh.harvard.edu/pph2/). If the SIFT prediction tolerance index score was less than 0.05, the variation was considered possibly damaging. Predictions made by PolyPhen-2 were assigned as “probably damaging,” “possibly damaging” or “benign.” Deletion mutations cannot be tested by either SIFT or PolyPhen-2. doi:10.1371/journal.Reported Not reported 20668451 18948947 17344846 21720365 19718025 19718025 19718025 19718025 19718025 21499247 21097718 stomach skin skin skin melanoma melanoma melanoma carcinoma skin melanoma skin melanoma skin melanoma ovary carcinoma ovary carcinoma TyrKc Ephrin_lbd TyrKc FN3 TyrKc Ephrin_lbd TyrKc Ephrin_lbd TyrKc lung carcinoma lung carcinoma TyrKc Between FN3 and TyrKc domains lung carcinoma Ephrin binding lung carcinoma FN3 lung carcinoma lung 18325633 carcinoma Ephrin_lbd Between Ephrin_lbd and GCC2_GCC3 domains lung carcinoma Ephrin_lbd 0.06 0.27 0.25 0.55 0.03 0.00 0.32 0.00 0.01 0.00 
1.00 0.00 0.05 0.44 0.76 0.06 lung carcinoma Ephrin_lbd 0.01 lung carcinoma 12926553 Between and Tyrkc and SAM domains not known large intestine carcinoma TyrKc 0.01 large intestine carcinoma Between TyrKc and SAM domains 0.22 large intestine carcinoma Between TyrKc and SAM domains 0.42 large intestine carcinoma Between GCC2_GCC3 and FN3 domains 0.00 large intestine carcinoma Between FN3 and TyrKc domains 0.22 central nervous system glioma Ephrin_lbd 0.42 central nervous system glioma TyrKc 0.04 central nervous system glioma TyrKc 0.00 PolyPhenCDS Mutation Pubmed IdPrimary TissueHistologyDomainsFunctional predictionp.A685Tc.2053G.Aprobably damaging with a score of 1.000 possibly damaging with a score of 0.671 probably damaging with a score of 0.971 probably damaging with a score of 0.983 probably damaging with a score of 0.999 benign with a score of 0.000 probably damaging with a score of 0.998 benign with a score of 0.004 not known probably damaging with a score of 0.999 probably damaging with a score of 0.999 probably damaging with a score of 0.999 possibly damaging with a score of 0.279 probably damaging with a score of 0.989 probably damaging with a score of 1.000 probably damaging with a score of 1.000 probably damaging with a score of 0.993 probably damaging with a score of 1.000 probably damaging with a score of 0.996 probably damaging with a score of 0.989 benign with a score of 0.000 possibly damaging with a score of 0.662 possibly damaging with a score of 0.881 probably damaging with a score of 0.993 benign with a score of 0.034 probably damaging with a score of 0.p.E860Kc.2578G.Ap.G106Dc.317G.Ap.A588Pc.1762G.Cp.D345Nc.1033G.Ap.D915Gc.2744A.Gp.G914V2741 G.Tp.R704Qc.2111G.Ap.915_917delc.2745del (CCCAGGGGA)p.A203Dc.608C.Ap.A85Tc.253G.Ap.K139Nc.417G.Tp.L269Mc.805C.Ap.Q498Hc.1494G/Cp.R52Cc.154C/Tp.P728Hc.2183C.Ap.R648Lc.1943G.Tp.P728Sc.2182C.Tp.L21Fc.63G.Tp.R704Wc.2110C.Tp.G404Sc.1210G.Ap.A688Gc.2063C.Gp.S152Fc.455C.Tp.R679Qc.2036G.Ap.S131Fc.392C.Tp.Q756Rc.2267A.GIdentification of EPHB6 MutationNote: The table contains data from the databases of http://www.sanger.ac.uk/genetics/CGP/cosmic/, http://strubiol.icr.ac.uk/extra/mokca, and the references were listed in the column of “Pubmed Id”. The NSCLC mutations identified in this study were marked as “not reported”. Two sequence homology-based tools were used to predict the potential impact of the identified non-synonymous substitutions on protein function: Sort Intolerant from Tolerant (SIFT; http://sift.bii.a-star.edu.sg/) and Polymorphism Phenotype (PolyPhen-2; http://genetics.bwh.harvard.edu/pph2/). If the SIFT prediction tolerance index score was less than 0.05, the variation was considered possibly damaging. Predictions made by PolyPhen-2 were assigned as “probably damaging,” “possibly damaging” or “benign.” Deletion mutations cannot be tested by either SIFT or PolyPhen-2. doi:10.1371/journal.