Testing strategy (age range for testing; colonoscopic surveillance interval)	Cost (proportion of total cost)
	Total costs	Proband gene panel testing	Relatives' genetic testing and counselling	dMMR tumour testing	Cancer treatment*	Colonoscopy
Stage 1 analysis
1. No testing	$110 474 000	—	—	—	$110 474 000 (100%)	—
7. MSI + MLH1 methylation (no age limit; 1 year)	$148 479 000	$2 268 750 (2%)	$2 163 910 (1%)	$5 038 780 (3%)	$82 555 200 (56%)	$56 452 200 (38%)
6. MSI + BRAF V600E (no age limit; 1 year)	$148 412 000	$2 234 670 (2%)	$2 165 240 (1%)	$5 038 730 (3%)	$82 338 100 (55%)	$56 635 400 (38%)
5. MSI (no age limit; 1 year)	$150 300 000	$6 353 170 (4%)	$2 164 630 (1%)	$2 815 080 (2%)	$82 021 700 (55%)	$56 945 300 (38%)
4. IHC + MLH1 methylation (no age limit; 1 year)	$148 225 000	$3 395 100 (2%)	$2 164 830 (1%)	$3 665 380 (2%)	$81 892 700 (55%)	$57 106 900 (39%)
3. IHC + BRAF V600E (no age limit; 1 year)	$148 193 000	$3 386 450 (2%)	$2 164 670 (1%)	$3 665 260 (2%)	$81 789 600 (55%)	$57 186 600 (39%)
2. IHC (no age limit; 1 year)	$148 861 000	$4 858 440 (3%)	$2 164 240 (1%)	$2 815 080 (2%)	$81 672 800 (55%)	$57 350 400 (39%)
8. Universal gene panel testing (no age limit; 1 year)	$175 199 000	$34 007 500 (19%)	$2 164 360 (1%)	—	$81 357 600 (46%)	$57 669 300 (33%)
Stage 2 analysis
1. No testing	$110 474 000	—	—	—	$110 474 000 (100%)	—
3.3. IHC + BRAF V600E (< 50 years; 2 years)	$114 170 000	$397 177 (< 1%)	$459 442 (< 1%)	$529 723 (< 1%)	$103 969 000 (91%)	$8 815 020 (8%)
3.2. IHC + BRAF V600E (< 50 years; 1 year)	$122 399 000	$397 207 (< 1%)	$459 183 (< 1%)	$529 606 (< 1%)	$103 565 000 (85%)	$17 448 200 (14%)
8.3. Universal gene panel testing (< 50 years; 2 years)	$116 060 000	$2 737 630 (2%)	$459 216 (< 1%)	—	$103 939 000 (90%)	$8 924 350 (8%)
8.2. Universal gene panel testing (< 50 years; 1 year)	$124 294 000	$2 737 530 (2%)	$459 167 (< 1%)	—	$103 439 000 (83%)	$17 658 000 (14%)
3.5. IHC + BRAF V600E (< 60 years; 2 years)	$117 501 000	$1 160 090 (1%)	$1 176 740 (1%)	$1 139 730 (1%)	$94 389 500 (80%)	$19 634 800 (17%)
8.5. Universal gene panel testing (< 60 years; 2 years)	$124 180 000	$9 014 050 (7%)	$1 176 590 (1%)	—	$94 144 300 (76%)	$19 844 700 (16%)
3.4. IHC + BRAF V600E (< 60 years; 1 year)	$135 409 000	$1 160 100 (1%)	$1 176 150 (1%)	$1 139 690 (1%)	$93 231 700 (69%)	$38 701 300 (29%)
8.4. Universal gene panel testing (< 60 years; 1 year)	$142 286 000	$9 013 810 (6%)	$1 176 350 (1%)	—	$92 987 300 (65%)	$39 108 900 (27%)
3.7. IHC + BRAF V600E (< 70 years; 2 years)	$119 303 000	$2 005 420 (2%)	$1 791 260 (2%)	$1 937 940 (2%)	$87 275 300 (73%)	$26 292 600 (22%)
8.7. Universal gene panel testing (< 70 years; 2 years)	$132 274 000	$17 064 300 (13%)	$1 790 520 (1%)	—	$86 883 100 (66%)	$26 536 500 (20%)
3.6. IHC + BRAF V600E (< 70 years; 1 year)	$142 963 000	$2 005 540 (1%)	$1 790 300 (1%)	$1 937 960 (1%)	$85 625 000 (60%)	$51 604 400 (36%)
8.6. Universal gene panel testing (< 70 years; 1 year)	$156 170 000	$17 064 100 (11%)	$1 790 140 (1%)	—	$85 239 800 (55%)	$52 076 300 (33%)
3.1. IHC + BRAF V600E (no age limit; 2 years)	$122 173 000	$3 386 260 (3%)	$2 165 780 (2%)	$3 665 230 (3%)	$83 693 900 (69%)	$29 261 400 (24%)
8.1. Universal gene panel testing (no age limit; 2 years)	$148 950 000	$34 007 900 (23%)	$2 164 800 (1%)	—	$83 259 600 (56%)	$29 517 400 (20%)
3. IHC + BRAF V600E (no age limit; 1 year)	$148 193 000	$3 386 450 (2%)	$2 164 670 (1%)	$3 665 260 (2%)	$81 789 600 (55%)	$57 186 600 (39%)
8. Universal gene panel testing (no age limit; 1 year)	$175 199 000	$34 007 500 (19%)	$2 164 360 (1%)	—	$81 357 600 (46%)	$57 669 300 (33%)

dMMR = DNA mismatch repair deficiency; IHC = immunohistochemistry; MSI = microsatellite instability.

^*Initial CRC treatment costs for the proband were not included in the analysis, as they were assumed to not be affected by LS testing.