Supplementary Table 1. Available resistance fold change data through literature search for the mutations/polymorphisms identified in the present study Target Mutationa Resistance fold change (compared with wild type of specific genotype)b GT 1a GT 1b GT 2a GT 3a GT 4a GT 5a GT 6a NS3 V36I protease V36L 2ASU [1] 1ASU [1] ≤1.3SIM [2] 1.3SIM [2] ≤1.3SIM [2] 2PAR [3] 1.7SIM [4] V36M 2ASU [1] 2ASU [1] 1.4GLE [5] <2DAN [6] 1.9GRA [5] 2SIM [4] 2PAR [3] >2.5VOX [7] 1.5SIM [8] 0.9VOX [8] Q41H T54A 0.4ASU [1] 0.4ASU [1] 0.8GRA [8] 1.3DAN [4] 0.5PAR [8] 1GLE [5] 0.4SIM [8] 1PAR [3] 0.6VOX [8] 0.6SIM [4] T54G T54S 1ASU [1] 1.2SIM [4] ≤1.3SIM [2] 1GLE [5] 1.1GRA [9] 0.4PAR [3] V55A 1ASU [1] 0.4GLE [5] 1PAR [3] V55G V55I 3ASU [1] 0.2GLE [5] 0.7GRA [5] 1PAR [3] V55P Y56F Q80D Q80G 9.8DAN [4] 1.8SIM [4] Q80K 3ASU [1] 6.5ASU [1] >2.5VOX [7] 8SIM [2] 8SIM [2] 0.9GLE [5] 2.3DAN [4] 1.1GRA [9] 7.7SIM [4] 3PAR [3] 11SIM [10] 0.8VOX [8] Q80L 1ASU [1] 1ASU [1] 2PAR [3] 1.9GRA [8] 1PAR [8] 2.1SIM [4] 1.3VOX [8] Q80M Q80N Q80R 2PAR [3] 4ASU [1] 0.4ASU [8] 3.5DAN [4] 0.1GRA [8] 6.9SIM [4] 0.2PAR [8] 0.5SIM [8] 0.8VOX [8] V107I S122G 1ASU [1] 0.5SIM [10] ≤1SIM [2] S122K S122N 1ASU [1] 1ASU [1] ≤1.3SIM [2] S122R 3ASU [1] 21SIM [10] 1.8GRA [9] S122T 1ASU [1] <1SIM [2] ≤1SIM [2] I132L I132V R155K 21ASU [1] 27ASU [1] 1ASU [8] 22ASU [8] 0.5GLE [5] 410DAN [11] 0.5GLE [5] 2.2GRA [8] 3GRA [9] 0.6GLE [5] 0.1GRA [5] 9.3PAR [8] 37PAR [3] 2.2GRA [12] 5.2PAR [5] 113SIM [8] 86SIM [10] 40PAR [3] >2.8SIM [8] 0.6VOX [8] 0.7VOX [8] 30SIM [4] 0.4VOX [8] 1.5VOX [8] R155P A156V NRASU [8] 20ASU [1] 5.4ASU [8] 23GRA[8] 9.9ASU [8] >2.5VOX [7] >2.5VOX [7] NRGRA [8] 63DAN [4] 1143GLE [5] >1334VOX [8] 3106GLE [5] NRPAR [8] 1786GLE [5] 14552b;GLE [5] 602GRA [5] NRSIM [8] 1200GRA [13] 187GRA [5] 155PAR [5] NRVOX [8] 21PAR [5] 4732b;GRA [5] >208SIM [8] 177SIM [4] 2.2PAR [5] >309VOX [8] 458VOX [8] 52b;PAR [5] 26SIM [8] >129VOX [8] >2.52b;VOX [7] V158I V158L V158M A166S A166T D168E 58ASU [1] 78ASU [1] 3.3GLE [5] 9.1ASU [8] 4.2GLE [5] 1.3GLE [5] 29DAN [11] 2.12b;GLE [5] 4.9GRA [8] 9.6GRA [5] 16GRA [12] 0.9GLE [5] 5.9GRA [5] 6.7PAR [8] 23PAR [5] 14PAR [3] 3.2GRA [12] 5.72b;GRA [5] 20SIM [8] 69SIM [8] 4PAR [3] 5.3PAR [5] 2.7VOX [8] 0.7VOX [8] 40SIM [4] 2.22b;PAR [5] 1.2VOX [8] D168Q >700SIM [2] D168T 205ASU [14] 300DAN [11] >2.5VOX [7] >2.5VOX [7] 49PAR [3] 308SIM [4] V170A 2ASU [1] <2DAN [6] 1.1GLE [5] 6.9GRA [8] 1PAR [3] 1.8SIM [4] 4.6VOX [8] V170I* 1ASU [1] 1ASU [1] <1SIM [2] ≤1SIM [2] 1.05DAN [11] M175L* NS5A K24A 38T24A;OMB [15] 1.3T24A;PIB [16] K24F K24G 3.3DAC [17] 43.3LED [17] 1.4VEL [17] K24Q K24R 2.1DAC [17] 1ELB [9] 3.7LED [17] 1.1VEL [17] K24S K24T 0.4ELB [9] M28A 4591DAC [18] 61ELB [19] 1195LED [17] 25.4VEL [17] M28C M28F 472b;L28F;OMB [15] 0.82b;L28F;PIB [16] M28G >22007DAC [17] >10368LED [17] 11940VEL [17] M28I 1.2DAC [20] 79L28I;OMB [15] 0.3LED [17] 1.1L28I;PIB [16] 1.2VEL [17] M28L 2L28M;DAC [21] 57.5L28M;LED [22] 2L28M;ELB [19] 2L28M;OMB [15] M28S 7735F28S;DAC [23] 4710F28S;OMB [15] 1.2F28S;PIB [16] M28T 682DAC [18] 20L28T;DAC [21] 659OMB [15] 15ELB [9] 661L28T;OMB [15] 1.7PIB [16] 61LED [24] 0.9L28T;PIB [16] ≤10ODA [25] 8965OMB [26] 2.1PIB [16] 7.5VEL [27] <10RUZ [28] M28V 1.3DAC [18] 1.3L28V;ELB [29] 66.9L28V;LED [22] 1ELB [9] 23L28V;OMB [15] 0.6LED [24] 1.1L28V;PIB [16] 58OMB [26] 1.8PIB [16] Q30A Q30H 1477DAC [18] ≤10R30H;DAC [30] 155R30H;DAC [31] 6ELB [9] 1215L30H;DAC [31] 183LED [24] 1.3L30H;PIB [16] ≤1ODA [25] 1.5L30H;VEL [27] 3OMB [15] 1PIB [16] <10RUZ [28] 2.3VEL [27] Q30K 24545DAC [18] 0.1K30Q;DAC [23] 62A30K;DAC [32] 1550LED [17] 50A30K;ELB [19] ≤10ODA [25] 50A30K;VEL [27] 10.4VEL [27] Q30L 3.7DAC [33] 4.3LED [17] 0.5VEL [27] Q30M Q30N Q30R 1227DAC [18] 1R30Q;DAC [21] 37L30R;LED [22] 16ELB [9] 0.4R30Q;OMB [15] 2.4L30R;VEL [27] 632LED [24] ≤10ODA [25] 800OMB [26] 1.7PIB [16] <10RUZ [28] 2.2VEL [27] Q30S 167 R30S;DAC [31] 4 L30S;ELB [34] 1.1L30S;VEL [27] Q30T 5DAC [17] 0.4A30T;DAC [32] 4.4LED [17] 1VEL [17] L31I 35.9DAC [17] 3.4DAC [17] >370LED [17] 29.4LED [17] 4.4VEL [27] 9.7VEL [17] L31M 341DAC [18] 3DAC [21] 141DAC [23] 70.8VEL [27] 878DAC [35] 10ELB [9] 1ELB [19] <12b;M31L;ELB [9] 554LED [24] 0.9OMB [15] ≤1ODA [25] ≤1ODA [25] 1.7VEL [27] ≤12b;ODA [25] 2OMB [26] 1.22b;PIB [16] 1.1PIB [16] 1.5VEL [27] <10RUZ [28] 16VEL [27] L31V 3386DAC [18] 23DAC [21] 5112b;OMB [15] 0.3VEL [27] 2.5 M31V;ELB [34] 458DAC [35] 68OMB [15] 61ELB [9] 4ELB [19] 0.52b;PIB [16] 243OMB [15] 1PIB [16] 683LED [17] 42.9LED [17] 10.1VEL [27] 0.8PIB [16] ≤1ODA [25] ≤1ODA [25] >100OMB [28] 8OMB [15] 1.3PIB [16] <10RUZ [28] <10RUZ [28] 2.3VEL [27] 67.5VEL [27] H58A 47T58A;DAC [35] 18T58A;OMB [15] 1.4T58A;PIB [16] H58C H58D 500DAC [18] 31P58D;DAC [17] 6ELB [9] 238P58D;LED [17] 1127LED [24] 1.8P58D;VEL [17] ≤10ODA [25] 243OMB [15] 1.1PIB [16] 7.3VEL [27] H58G H58L H58N 532T58N;DAC [35] 101T58N;OMB [15] 1.8T58N;PIB [16] H58P 1.2DAC [18] 1P58H;DAC [21] 0.5OMB [26] H58Q H58R H58S 1P58S;DAC [21] 48T58S;DAC [35] 18T58S;OMB [15] H58T 1.5P58T;LED [22] H58Y E62A E62D 2DAC [20] E62G E62H E62I E62K E62L 2S62L;DAC [32] E62M E62N E62Q E62R E62S E62T E62V E62Y A92C A92E 0.8DAC [17] 0.3LED [17] 0.7VEL [17] A92G A92P 1ELB [19] A92S A92T 1.3DAC [17] 15.2LED [17] 1.2VEL [17] A92V Y93C 1864DAC [18] 3.5DAC [33] 1.2VEL [27] 11ELB [9] 1.7ELB [29] 1602LED [24] 5.3LED [17] ≤100ODA [25] 0.2VEL [27] 1675OMB [15] 1.7PIB [16] 3.8VEL [27] Y93H 5432DAC [18] 19DAC [21] 749DAC [23] 2752DAC [32] 169DAC [31] 220ELB [9] 17ELB [19] 45.7VEL [27] 485ELB [19] 7.5ELB [34] 1677LED [24] 1807LED [17] >1000LED [28] 135LED [22] ≤1000ODA [25] ≤10ODA [25] 6728OMB [15] 2.9VEL [27] 41383OMB [15] 77OMB [15] 2.3PIB [16] 6.7PIB [16] 0.6PIB [16] 723.5VEL [27] <10RUZ [28] <10RUZ [28] 609.1VEL [27] 3.3VEL [27] Y93I Y93R 497.2VEL [27] 454DAC [31] Y93S 2734DAC [17] 3.4DAC [17] 1626LED [17] 141.6LED [17] 1013OMB [15] 0.6VEL [27] 63.9VEL [27] Y93T V121I* 0.2ELB [19] NS5B A15C A15G 0.84S15G;SOF [36] A15I A15N A15R A15S A15T A15V L159F 1.2SOF [17] 1.3SOF [37] 1.6SOF [37] 1SOF [37] I239L I239V S282C S282R S282T 8.4SOF [17] 0.8BEC [38] 2.4SOF [10] 3.5SOF [37] 6.1SOF[22] 18.1SOF [10] 7.8SOF [10] 8.8SOF [37] 16.22b;SOF [37] C316G C316H >100DAS [39] >100DAS [39] 0.9SOF [37] 0.9SOF [37] C316N 1.6SOF [37] 5DAS [40] 1SOF [37] C316R C316Y 1472DAS [40] 0.4BEC [38] 1569DAS [40] 0.61SOF[36] L320R L320Y V321F V321I 0.84SOF [36] 0.7SOF [22] V321Y S368A S368P N411D N411S 84DAS [40] N411T M414A M414I 8DAS [26] 2-20DAS [39] M414L M414Q M414S M414V 32DAS [40] 47DAS [40, 41] L419I L419V A421M A421S A421T A421V R422K 144.7RAD [42] 814.6RAD [42] M423A M423I 10.6RAD [42] 4.6RAD [42] M423T 15.8RAD [42] 1BEC [38] 0.4DAS [40] 19.3RAD [42] 0.9SOF [36] M423V 8.5RAD [42] 7RAD [42] M426A M426C M426F M426I M426L 1.1RAD [42] M426T M426V C445F 16DAS [40] 1.6SOF [43] C445W C445Y Y448C 940DAS [40] 414DAS [40] C451A C451H C451I C451N C451R C451S 16DAS [40] C451T C451V C451W C451Y I482L 26.1RAD [42] 51.4RAD [42] A486G A486S A486V 39.6RAD [42] 49.8RAD [42] V494A 17.4RAD [42] 18.1RAD [42] 3.4BEC [44] 17BEC [44] V494C V494I 0.6RAD [42] V494M V494S 34C494S;BEC [44] P495L 32BEC [44] 53BEC [44] 1SOF [36] P496S V499A* 1.6BEC [44] 1.4DAS [40] V499I V499M V499T A553G A553P A553S A553T 152DAS [26] A553V 120DAS [40] G554A G554C G554S 198DAS [26] S556A S556C S556D S556G 30DAS [40] 11DAS [40] S556N 29DAS [40] S556R >100DAS [39] D559H D559I D559N D559Q NS3 protease: Fold change 0 to <10 (highlighted in green), Fold change 10 to 30 (highlighted in orange), Fold change >30 (highlighted in red) NS5A: Fold change 0 to <10 (highlighted in green), Fold change 10 to 50 (highlighted in orange), Fold change >50 (highlighted in red) NS5B: Fold change 0 to <10 (highlighted in green), Fold change 10 to 50 (highlighted in orange), Fold change >50 (highlighted in red) a = residue index as per GT 1a; *residue at this position has been swapped (i.e.