Table S7. Detected 350 Pathogenic Variants in This Study Position Allele Causative Nucleotide Amino Acid Variant Chr

Supplementary material J Med Genet

Table S7. Detected 350 pathogenic variants in this study Position Allele Causative Nucleotide Amino acid Variant Chr. rsID Type of variant (bp) (REF/ALT) gene change change Class 1 46,657,820 G/A rs745343484 POMGNT1 c.1489C>T p.(Arg497*) Stopgain Class 2 1 68,895,518 G/A rs121917745 RPE65 c.1543C>T p.(Arg515Trp) Missense Class 1 1 68,910,339 G/A rs61752877 RPE65 c.370C>T p.(Arg124*) Stopgain Class 1 1 94,463,537 G/T rs61753045 ABCA4 c.6609C>A p.(Tyr2203*) Stopgain Class 1 1 94,466,426 G/A rs61750654 ABCA4 c.6445C>T p.(Arg2149*) Stopgain Class 1 1 94,466,628 G/A rs61750648 ABCA4 c.6316C>T p.(Arg2106Cys) Missense Class 1 1 94,473,266 C/T rs61750639 ABCA4 c.5929G>A p.(Gly1977Ser) Missense Class 1 1 94,476,417 C/T rs62642563 ABCA4 c.5653G>A p.(Glu1885Lys) Missense Class 1 1 94,495,021 C/T rs568792949 ABCA4 c.4519G>A p.(Gly1507Arg) Missense Class 1 1 94,495,078 A/G rs61750146 ABCA4 c.4462T>C p.(Cys1488Arg) Missense Class 1 1 94,496,008 C/T rs61750142 ABCA4 c.4328G>A p.(Arg1443His) Missense Class 1 1 94,496,039 C/T rs56357060 ABCA4 c.4297G>A p.(Val1433Ile) Missense Class 1 1 94,496,610 C/T rs62642573 ABCA4 c.4195G>A p.(Glu1399Lys) Missense Class 1 1 94,508,358 G/A rs763267492 ABCA4 c.3287C>T p.(Ser1096Leu) Missense Class 1 1 94,512,499 T/C rs201471607 ABCA4 c.2894A>G p.(Asn965Ser) Missense Class 1 1 94,528,259 A/C rs61749411 ABCA4 c.1811T>G p.(Ile604Ser) Missense Class 1 1 94,528,666 A/C rs61751385 ABCA4 c.1760+2T>G p.? Canonical splice site variant Class 1 1 94,543,268 C/T rs140482171 ABCA4 c.1532G>A p.(Arg511His) Missense Class 1 1 94,543,269 G/A rs752786160 ABCA4 c.1531C>T p.(Arg511Cys) Missense Class 1 1 94,564,355 G/A rs62645952 ABCA4 c.763C>T p.(Arg255Cys) Missense Class 1 1 94,568,569 A/C - ABCA4 c.570+2T>G p.? Canonical splice site variant Class 2 1 94,568,699 CTACA/C - ABCA4 c.443-5_443-2delTGTA p.? Canonical splice site variant Class 2 1 150,315,783 A/G - PRPF3 c.1283-2A>G p.? Canonical splice site variant Class 2 1 197,297,564 A/AT - CRB1 c.84dupT p.(Lys29fs) Frameshift insertion Class 2 1 197,297,621 A/AT - CRB1 c.145dupT p.(Ser49fs) Frameshift insertion Class 2 1 197,298,133 GGTAA/G - CRB1 c.652+3_652+6delAAGT p.? Canonical splice site variant Class 1 1 197,390,534 C/T rs114342808 CRB1 c.1369C>T p.(Arg457*) Stopgain Class 1 1 197,390,718 G/A - CRB1 c.1553G>A p.(Cys518Tyr) Missense Class 1 1 197,396,685 C/T rs150412614 CRB1 c.2023C>T p.(Arg675*) Stopgain Class 1 1 197,396,763 G/A rs767648174 CRB1 c.2101G>A p.(Gly701Ser) Missense Class 1 1 197,396,917 C/T rs142857810 CRB1 c.2255C>T p.(Thr752Met) Missense Class 1 1 197,398,616 G/A rs114052315 CRB1 c.2642G>A p.(Arg881Gln) Missense Class 1 1 197,398,711 G/A rs114630940 CRB1 c.2737G>A p.(Val913Met) Missense Class 1 1 215,802,154 A/AC - USH2A c.15519+1dupG p.? Canonical splice site variant Class 2 1 215,807,865 G/C rs527236122 USH2A c.15233C>G p.(Pro5078Arg) Missense Class 1 1 215,807,920 A/G rs752377040 USH2A c.15178T>C p.(Ser5060Pro) Missense Class 1 1 215,824,034 G/A rs527236126 USH2A c.14243C>T p.(Ser4748Phe) Missense Class 1 1 215,824,071 CT/C - USH2A c.14205delA p.(Glu4736fs) Frameshift deletion Class 2 1 215,844,430 A/G - USH2A c.14017T>C p.(Tyr4673His) Missense Class 1 1 215,844,437 G/T - USH2A c.14010C>A p.(Tyr4670*) Stopgain Class 2 1 215,844,600 C/A rs527236124 USH2A c.13847G>T p.(Gly4616Val) Missense Class 1 1 215,847,914 T/C rs139474806 USH2A c.13339A>G p.(Met4447Val) Missense Class 1 1 215,847,947 AT/A - USH2A c.13305delA p.(Lys4435fs) Frameshift deletion Class 2 1 215,848,137 CATTT/C rs768161313 USH2A c.13112_13115delAAAT p.(Gln4371fs) Frameshift deletion Class 2 1 215,848,243 G/A rs527236137 USH2A c.13010C>T p.(Thr4337Met) Missense Class 1 1 215,848,806 C/T - USH2A c.12447G>A p.(Trp4149*) Stopgain Class 2 1 215,901,625 TAG/T - USH2A c.11811_11812delCT p.(Tyr3938fs) Frameshift deletion Class 2 1 215,931,998 A/C rs749726310 USH2A c.11328T>G p.(Tyr3776*) Stopgain Class 2 1 215,933,077 C/T rs527236139 USH2A c.11156G>A p.(Arg3719His) Missense Class 1 1 215,933,130 A/T - USH2A c.11103T>A p.(Tyr3701*) Stopgain Class 2 1 215,940,071 T/G rs150822759 USH2A c.10999A>C p.(Thr3667Pro) Missense Class 1 1 215,953,220 G/T rs727505166 USH2A c.10904C>A p.(Thr3635Asn) Missense Class 1 1 215,953,265 A/G rs779716464 USH2A c.10859T>C p.(Ile3620Thr) Missense Class 1 1 215,956,121 T/C rs527236119 USH2A c.10544A>G p.(Asp3515Gly) Missense Class 1 1 215,972,408 A/G rs111033263 USH2A c.9799T>C p.(Cys3267Arg) Missense Class 1 1 215,987,206 T/C rs745539518 USH2A c.9611A>G p.(His3204Arg) Missense Class 1 1 215,990,338 C/T rs760225886 USH2A c.9570+1G>A p.? Canonical splice site variant Class 1 1 216,017,635 C/A - USH2A c.9258+1G>T p.? Canonical splice site variant Class 2 1 216,017,650 T/C rs527689947 USH2A c.9244A>G p.(Ile3082Val) Missense Class 1 1 216,051,224 T/C rs397518039 USH2A c.8559-2A>G p.? Canonical splice site variant Class 1 1 216,052,410 C/T rs201863550 USH2A c.8254G>A p.(Gly2752Arg) Missense Class 1 1 216,062,331 G/A - USH2A c.7660C>T p.(Gln2554*) Stopgain Class 2 1 216,074,094 C/T rs397518030 USH2A c.7451+3G>A p.? Non-canonical splice site variant Class 1 1 216,108,006 G/A - USH2A c.7252C>T p.(Gln2418*) Stopgain Class 2 1 216,143,987 C/A rs199840367 USH2A c.6937G>T p.(Gly2313Cys) Missense Class 1 1 216,144,109 G/A rs776972526 USH2A c.6815C>T p.(Thr2272Met) Missense Class 1 1 216,243,539 C/T rs150143291 USH2A c.5953G>A p.(Glu1985Lys) Missense Class 1 1 216,243,634 G/C rs41302239 USH2A c.5858C>G p.(Ala1953Gly) Missense Class 1 1 216,246,607 G/A rs144768593 USH2A c.5608C>T p.(Arg1870Trp) Missense Class 1 1 216,348,605 G/A rs758095361 USH2A c.4616C>T p.(Thr1539Ile) Missense Class 1 1 216,373,181 CCTT/C - USH2A c.3596_3598delAAG p.(Glu1199del) Non-frameshift deletion Class 1 1 216,419,934 A/C rs201527662 USH2A c.2802T>G p.(Cys934Trp) Missense Class 1 1 216,419,960 G/A rs749621457 USH2A c.2776C>T p.(Arg926Cys) Missense Class 1 1 216,420,083 G/A rs746071929 USH2A c.2653C>T p.(His885Tyr) Missense Class 1 1 216,420,322 C/G rs587783023 USH2A c.2414G>C p.(Gly805Ala) Missense Class 1 1 216,424,240 C/T rs771583281 USH2A c.2167+5G>A p.? Non-canonical splice site variant Class 1 1 216,465,564 AAGTGCTCAAAAGGAAATGG/A - USH2A.1774_1792delCCATTTCCTTTTGAGCAp.(Pro592fs) Frameshift deletion Class 2 1 216,465,628 A/G - USH2A c.1729T>C p.(Cys577Arg) Missense Class 1 1 216,465,679 G/C rs147509797 USH2A c.1678C>G p.(Pro560Ala) Missense Class 1 1 216,497,571 C/A - USH2A c.1267G>T p.(Gly423*) Stopgain Class 2 1 216,498,742 C/T rs148848581 USH2A c.1048G>A p.(Val350Ile) Missense Class 1

Koyanagi Y, et al. J Med Genet 2019; 0:662–670. doi: 10.1136/jmedgenet-2018-105691 Supplementary material J Med Genet

1 216,500,979 C/T rs111033280 USH2A c.802G>A p.(Gly268Arg) Missense Class 1 1 216,592,017 C/A rs527236123 USH2A c.490G>T p.(Val164Phe) Missense Class 1 1 216,595,473 C/A rs377254440 USH2A c.206G>T p.(Ser69Ile) Missense Class 1 2 27,679,521 C/G - IFT172 c.3229-1G>C p.? Canonical splice site variant Class 2 2 27,704,128 C/T rs775935517 IFT172 c.571-1G>A p.? Canonical splice site variant Class 2 2 29,287,898 G/A rs201933656 C2orf71 c.3704C>T p.(Pro1235Leu) Missense Class 1 2 29,293,768 ATG/A - C2orf71 c.3358_3359delCA p.(His1120fs) Frameshift deletion Class 2 2 29,296,721 T/C rs761117759 C2orf71 c.407A>G p.(Glu136Gly) Missense Class 1 2 29,297,043 G/A rs201706430 C2orf71 c.85C>T p.(Arg29Trp) Missense Class 1 2 96,945,225 CT/C - SNRNP200 c.5096delA p.(Glu1699fs) Frameshift deletion Class 2 2 96,953,706 G/A rs267607077 SNRNP200 c.3260C>T p.(Ser1087Leu) Missense Class 1 2 96,956,213 C/T rs786205529 SNRNP200 c.2593G>A p.(Gly865Ser) Missense Class 1 2 96,958,826 G/A - SNRNP200 c.2044C>T p.(Pro682Ser) Missense Class 1 2 96,958,828 C/T rs527236113 SNRNP200 c.2042G>A p.(Arg681His) Missense Class 1 2 96,958,829 G/A - SNRNP200 c.2041C>T p.(Arg681Cys) Missense Class 1 2 112,686,859 CA/C rs527236083 MERTK c.225delA p.(Gly76fs) Frameshift deletion Class 1 2 112,686,978 T/G - MERTK c.343T>G p.(Cys115Gly) Missense Class 1 2 112,702,554 G/A rs781470358 MERTK c.500G>A p.(Arg167His) Missense Class 1 2 112,777,089 C/T - MERTK c.2179C>T p.(Arg727*) Stopgain Class 1 2 182,430,822 AC/A - CERKL c.639delG p.(Ser214fs) Frameshift deletion Class 2 2 182,468,592 C/T rs746595127 CERKL c.453G>A p.(Trp151*) Stopgain Class 2 2 234,243,724 CA/C rs754158163 SAG c.926delA p.(Asn309fs) Frameshift deletion Class 1 2 234,959,477 T/TTATG - SPP2 c.49_52dupATGT p.(Phe18fs) Frameshift insertion Class 2 3 3,179,090 C/T rs759826831 TRNT1 c.295C>T p.(Arg99Trp) Missense Class 1 3 3,186,325 AAGTT/A rs769317780 TRNT1 c.542_545delTTAG p.(Val181fs) Frameshift deletion Class 2 3 97,503,895 T/C - ARL6 c.349+2T>C p.? Canonical splice site variant Class 2 3 100,947,651 C/G rs750183083 IMPG2 c.3703G>C p.(Glu1235Gln) Missense Class 1 3 100,948,252 ATC/A - IMPG2 c.3603_3604delGA p.(Gln1201fs) Frameshift deletion Class 2 3 100,951,761 C/A - IMPG2 c.3097G>T p.(Glu1033*) Stopgain Class 2 3 100,962,459 G/A rs267606876 IMPG2 c.2716C>T p.(Arg906*) Stopgain Class 1 3 100,964,926 C/T - IMPG2 c.1263G>A p.(Trp421*) Stopgain Class 2 3 101,038,560 G/GGTCC - IMPG2 c.198_201dupGGAC p.(Arg68fs) Frameshift insertion Class 2 3 101,038,669 GGTTT/G - IMPG2 c.89_92delAAAC p.(Gln30fs) Frameshift deletion Class 2 3 129,247,587 C/A - RHO c.11C>A p.(Thr4Lys) Missense Class 1 3 129,247,626 C/T rs104893769 RHO c.50C>T p.(Thr17Met) Missense Class 1 3 129,247,644 C/T - RHO c.68C>T p.(Pro23Leu) Missense Class 1 3 129,247,772 A/T - RHO c.196A>T p.(Lys66*) Stopgain Class 2 3 129,247,809 A/T - RHO c.233A>T p.(Asn78Ile) Missense Class 1 3 129,247,839 T/C - RHO c.263T>C p.(Leu88Pro) Missense Class 1 3 129,247,892 G/A rs104893773 RHO c.316G>A p.(Gly106Arg) Missense Class 1 3 129,249,737 C/T - RHO c.380C>T p.(Ser127Phe) Missense Class 1 3 129,249,760 C/T rs104893775 RHO c.403C>T p.(Arg135Trp) Missense Class 1 3 129,249,848 C/T rs104893793 RHO c.491C>T p.(Ala164Val) Missense Class 1 3 129,251,104 G/A - RHO c.541G>A p.(Glu181Lys) Missense Class 1 3 129,251,125 G/A rs527236100 RHO c.562G>A p.(Gly188Arg) Missense Class 1 3 129,251,131 G/A rs104893779 RHO c.568G>A p.(Asp190Asn) Missense Class 1 3 129,252,462 C/A - RHO c.948C>A p.(Cys316*) Stopgain Class 2 3 129,252,544 C/T rs104893778 RHO c.1030C>T p.(Gln344*) Stopgain Class 1 3 129,252,554 C/T rs29001566 RHO c.1040C>T p.(Pro347Leu) Missense Class 1 3 150,659,395 C/T rs779258184 CLRN1 c.407G>A p.(Gly136Glu) Missense Class 1 3 150,690,241 A/G - CLRN1 c.253+2T>C p.? Canonical splice site variant Class 2 3 170,185,076 G/A rs181011740 SLC7A14 c.2083C>T p.(Arg695Cys) Missense Class 1 4 647,715 C/G - PDE6B c.786C>G p.(Tyr262*) Stopgain Class 2 4 647,740 G/A rs374156343 PDE6B c.811G>A p.(Glu271Lys) Missense Class 1 4 654,364 G/A rs527236091 PDE6B c.1576G>A p.(Glu526Lys) Missense Class 1 4 654,392 T/A rs527236088 PDE6B c.1604T>A p.(Ile535Asn) Missense Class 1 4 655,977 C/T rs121918581 PDE6B c.1669C>T p.(His557Tyr) Missense Class 1 4 656,978 T/G - PDE6B c.1083+2T>G p.? Canonical splice site variant Class 2 4 657,592 C/T rs373037737 PDE6B c.1954C>T p.(Gln652*) Stopgain Class 1 4 657,656 T/TC - PDE6B c.2019dupC p.(Lys674fs) Frameshift insertion Class 2 4 16,002,118 C/T - PROM1 c.1551+1G>A p.? Canonical splice site variant Class 2 4 16,014,922 G/A rs137853006 PROM1 c.1117C>T p.(Arg373Cys) Missense Class 1 4 47,939,081 AC/A - CNGA1 c.1429delG p.(Val477fs) Frameshift deletion Class 1 4 47,939,241 G/A rs369717052 CNGA1 c.1270C>T p.(Arg424*) Stopgain Class 1 4 47,939,522 T/C rs527236059 CNGA1 c.989A>G p.(Asp330Gly) Missense Class 1 4 47,939,672 C/T rs375412499 CNGA1 c.839G>A p.(Arg280His) Missense Class 1 4 47,942,792 G/A rs759781200 CNGA1 c.652C>T p.(Arg218*) Stopgain Class 1 4 47,951,883 AG/A rs749012133 CNGA1 c.265delC p.(Leu89fs) Frameshift deletion Class 1 4 47,954,625 G/A rs199636364 CNGA1 c.94C>T p.(Arg32*) Stopgain Class 1 4 187,126,386 G/A rs199476198 CYP4V2 c.1020G>A p.(Trp340*) Stopgain Class 1 4 187,130,393 G/A rs202204817 CYP4V2 c.1372G>A p.(Val458Met) Missense Class 1 5 149,274,790 G/A rs759589388 PDE6A c.1684C>T p.(Arg562Trp) Missense Class 1 5 149,277,925 C/G rs781616522 PDE6A c.1407+1G>C p.? Canonical splice site variant Class 2 5 149,286,908 G/A rs121918577 PDE6A c.1032C>T p.(Ser344Ser) Synonymous Class 1 5 149,310,665 C/T rs148938083 PDE6A c.784G>A p.(Ala262Thr) Missense Class 1 6 10,804,063 C/T rs527236080 MAK c.553G>A p.(Ala185Thr) Missense Class 1 6 10,804,065 C/T - MAK c.551G>A p.(Trp184*) Stopgain Class 2 6 10,813,894 G/GC rs527236082 MAK c.340dupG p.(Ala114fs) Frameshift insertion Class 1 6 35,471,413 G/A rs200769197 TULP1 c.1246C>T p.(Arg416Cys) Missense Class 1 6 35,471,593 A/G rs121909076 TULP1 c.1145T>C p.(Phe382Ser) Missense Class 1 6 42,672,117 TGAG/T - PRPH2 c.811_813delCTC p.(Leu271del) Non-frameshift deletion Class 1 6 42,672,199 G/T rs61755816 PRPH2 c.732C>A p.(Asn244Lys) Missense Class 1 6 42,672,223 G/C - PRPH2 c.708C>G p.(Tyr236*) Stopgain Class 1 6 42,672,273 G/A rs61755809 PRPH2 c.658C>T p.(Arg220Trp) Missense Class 1 6 42,672,297 T/C rs61755800 PRPH2 c.634A>G p.(Ser212Gly) Missense Class 1

Koyanagi Y, et al. J Med Genet 2019; 0:662–670. doi: 10.1136/jmedgenet-2018-105691 Supplementary material J Med Genet

6 42,672,299 A/AT - PRPH2 c.631_632insA p.(Phe211fs) Frameshift insertion Class 2 6 42,672,302 G/A rs61755798 PRPH2 c.629C>T p.(Pro210Leu) Missense Class 1 6 42,672,342 T/C rs62645931 PRPH2 c.589A>G p.(Lys197Glu) Missense Class 1 6 42,689,559 G/A rs61755792 PRPH2 c.514C>T p.(Arg172Trp) Missense Class 1 6 42,689,565 C/T rs61755791 PRPH2 c.508G>A p.(Gly170Ser) Missense Class 1 6 42,689,574 C/T rs527236098 PRPH2 c.499G>A p.(Gly167Ser) Missense Class 1 6 64,430,623 CTT/C - EYS c.9302_9303delAA p.(Gln3101fs) Frameshift deletion Class 2 6 64,430,718 A/G rs183589498 EYS c.9209T>C p.(Ile3070Thr) Missense Class 1 6 64,430,739 CTG/C - EYS c.9186_9187delCA p.(Asn3062fs) Frameshift deletion Class 1 6 64,430,868 A/G - EYS c.9059T>C p.(Ile3020Thr) Missense Class 1 6 64,431,058 CA/C - EYS c.8868delT p.(Ala2957fs) Frameshift deletion Class 2 6 64,431,067 A/G rs79036642 EYS c.8860T>C p.(Phe2954Leu) Missense Class 1 6 64,431,069 G/T - EYS c.8858C>A p.(Ser2953*) Stopgain Class 1 6 64,431,115 G/T - EYS c.8812C>A p.(Leu2938Met) Missense Class 1 6 64,431,122 G/T rs527236067 EYS c.8805C>A p.(Tyr2935*) Stopgain Class 1 6 64,431,130 ATGAT/A - EYS c.8793_8796delATCA p.(Gln2931fs) Frameshift deletion Class 2 6 64,431,239 AG/A - EYS c.8687delC p.(Thr2896fs) Frameshift deletion Class 2 6 64,431,382 G/A - EYS c.8545C>T p.(Arg2849*) Stopgain Class 2 6 64,431,624 ATAGT/A - EYS c.8299_8302delACTA p.(Thr2767fs) Frameshift deletion Class 2 6 64,431,654 TGAACG/T - EYS c.8268_8272delCGTTC p.(Val2757fs) Frameshift deletion Class 2 6 64,431,683 T/TA - EYS c.8243dupT p.(Leu2748fs) Frameshift insertion Class 1 6 64,431,691 C/G - EYS c.8236G>C p.(Asp2746His) Missense Class 1 6 64,436,439 C/G - EYS c.8206G>C p.(Ala2736Pro) Missense Class 1 6 64,436,502 G/A - EYS c.8143C>T p.(Arg2715*) Stopgain Class 2 6 64,436,507 TGAAAG/T rs751629543 EYS c.8133_8137delCTTTC p.(Phe2712fs) Frameshift deletion Class 1 6 64,472,506 C/T rs527236066 EYS c.7919G>A p.(Trp2640*) Stopgain Class 1 6 64,487,975 G/A - EYS c.7822C>T p.(Gln2608*) Stopgain Class 2 6 64,487,987 G/A - EYS c.7810C>T p.(Arg2604Cys) Missense Class 1 6 64,498,054 CTG/C - EYS c.7665_7666delCA p.(Tyr2555fs) Frameshift deletion Class 1 6 64,499,037 C/G - EYS c.7492G>C p.(Ala2498Pro) Missense Class 1 6 64,694,282 CA/C rs527236069 EYS c.7048delT p.(Cys2350fs) Frameshift deletion Class 1 6 64,694,354 CG/TA - EYS c.6976_6977delinsTA p.(Arg2326*) Stopgain Class 2 6 64,776,241 TA/T rs752953889 EYS c.6714delT p.(Ile2239fs) Frameshift deletion Class 1 6 64,791,758 T/C rs184448644 EYS c.6562A>G p.(Ile2188Val) Missense Class 1 6 64,791,763 C/T rs527236068 EYS c.6557G>A p.(Gly2186Glu) Missense Class 1 6 65,146,159 C/G - EYS c.5836-1G>C p.? Canonical splice site variant Class 2 6 65,300,802 C/CT rs527236065 EYS c.4957dupA p.(Ser1653fs) Frameshift insertion Class 1 6 65,300,863 T/C rs77523865 EYS c.4897A>G p.(Lys1633Glu) Missense Class 1 6 65,301,202 CT/C rs768092887 EYS c.4557delA p.(Ala1520fs) Frameshift deletion Class 1 6 65,301,747 CTG/C - EYS c.4011_4012delCA p.(His1337fs) Frameshift deletion Class 2 6 65,303,078 A/C rs368856942 EYS c.3809T>G p.(Val1270Gly) Missense Class 1 6 65,327,400 C/A - EYS c.3595G>T p.(Glu1199*) Stopgain Class 2 6 65,596,690 T/G rs762212630 EYS c.2892A>C p.(Glu964Asp) Missense Class 1 6 65,596,696 G/C rs766153322 EYS c.2886C>G p.(Phe962Leu) Missense Class 1 6 65,655,707 GT/G - EYS c.2359delA p.(Thr787fs) Frameshift deletion Class 2 6 65,655,727 G/T - EYS c.2340C>A p.(Cys780*) Stopgain Class 2 6 66,054,036 A/ACTTT - EYS c.1493_1494insAAAG p.(Asp498fs) Frameshift insertion Class 2 6 66,094,278 C/A - EYS c.1299+1G>T p.? Canonical splice site variant Class 2 6 66,094,366 G/GT rs764163418 EYS c.1211dupA p.(Asn404fs) Frameshift insertion Class 1 6 66,115,066 C/T - EYS c.1056+1G>A p.? Canonical splice site variant Class 2 6 66,115,180 CA/C - EYS c.942delT p.(Ala315fs) Frameshift deletion Class 2 6 66,204,672 C/T - EYS c.632G>A p.(Cys211Tyr) Missense Class 1 6 66,204,697 G/A - EYS c.607C>T p.(Gln203*) Stopgain Class 2 6 66,204,778 C/A - EYS c.526G>T p.(Glu176*) Stopgain Class 2 6 66,204,854 TG/T - EYS c.449delC p.(Thr150fs) Frameshift deletion Class 2 6 66,205,098 GA/G - EYS c.205delT p.(Ser69fs) Frameshift deletion Class 2 6 66,205,163 T/A rs267601099 EYS c.141A>T p.(Glu47Asp) Missense Class 1 6 66,205,186 CAT/C - EYS c.116_117delAT p.(Tyr39fs) Frameshift deletion Class 2 6 66,205,227 C/T rs528733427 EYS c.77G>A p.(Arg26Gln) Missense Class 1 6 66,205,269 A/G rs755947942 EYS c.35T>C p.(Met12Thr) Missense Class 1 7 128,035,291 GTAC/TT - IMPDH1 c.1296_1299delinsAA p.(Val432fs) Frameshift indel Class 2 7 128,038,575 T/C - IMPDH1 c.967A>G p.(Lys323Glu) Missense Class 1 7 128,038,611 C/T rs121912550 IMPDH1 c.931G>A p.(Asp311Asn) Missense Class 1 7 128,049,404 GT/G - IMPDH1 c.192delA p.(Glu64fs) Frameshift deletion Class 2 7 138,602,574 ACT/A - KIAA1549 c.1796_1797delAG p.(Glu599fs) Frameshift deletion Class 2 8 10,464,405 C/G rs143762729 RP1L1 c.7203G>C p.(Ter2401Tyrext*?) Stoploss Class 2 8 10,466,207 C/A rs764029725 RP1L1 c.5401G>T p.(Gly1801*) Stopgain Class 2 8 10,466,958 A/C rs760013790 RP1L1 c.4650T>G p.(Asn1550Lys) Missense Class 1 8 10,467,647 G/A - RP1L1 c.3961C>T p.(Gln1321*) Stopgain Class 2 8 10,467,686 C/A rs778117952 RP1L1 c.3922G>T p.(Glu1308*) Stopgain Class 2 8 10,468,578 TCCCG/T - RP1L1 c.3026_3029delCGGG p.(Ala1009fs) Frameshift deletion Class 2 8 10,469,582 T/A rs752248086 RP1L1 c.2026A>T p.(Ser676Cys) Missense Class 1 8 10,469,636 G/A rs527236107 RP1L1 c.1972C>T p.(Arg658*) Stopgain Class 1 8 10,470,107 C/A - RP1L1 c.1501G>T p.(Glu501*) Stopgain Class 2 8 10,470,320 G/A - RP1L1 c.1288C>T p.(Gln430*) Stopgain Class 2 8 10,480,129 G/A - RP1L1 c.583C>T p.(Gln195*) Stopgain Class 2 8 10,480,309 G/A - RP1L1 c.403C>T p.(Gln135*) Stopgain Class 2 8 10,480,687 G/A - RP1L1 c.25C>T p.(Gln9*) Stopgain Class 2 8 43,028,883 C/T rs121908282 HGSNAT c.848C>T p.(Pro283Leu) Missense Class 1 8 43,037,323 C/T rs752939204 HGSNAT c.1048C>T p.(Gln350*) Stopgain Class 2 8 55,533,978 GC/G - RP1 c.458delC p.(Pro153fs) Frameshift deletion Class 2 8 55,534,709 TG/T rs527236105 RP1 c.650delG p.(Gly217fs) Frameshift deletion Class 1 8 55,537,442 G/GA - RP1 c.1001dupA p.(Met335fs) Frameshift insertion Class 2 8 55,537,489 G/A - RP1 c.1047G>A p.(Trp349*) Stopgain Class 2 8 55,537,939 CAT/C rs765129639 RP1 c.1498_1499delAT p.(Met500fs) Frameshift deletion Class 1

Koyanagi Y, et al. J Med Genet 2019; 0:662–670. doi: 10.1136/jmedgenet-2018-105691 Supplementary material J Med Genet

8 55,538,423 G/T - RP1 c.1981G>T p.(Glu661*) Stopgain Class 1 8 55,538,471 C/T rs104894082 RP1 c.2029C>T p.(Arg677*) Stopgain Class 1 8 55,538,474 C/T - RP1 c.2032C>T p.(Gln678*) Stopgain Class 1 8 55,538,507 C/T - RP1 c.2065C>T p.(Gln689*) Stopgain Class 1 8 55,538,661 C/G - RP1 c.2219C>G p.(Ser740*) Stopgain Class 1 8 55,539,032 ATAACT/A - RP1 c.2592_2596delAACTT p.(Thr865fs) Frameshift deletion Class 2 8 55,539,036 CT/C - RP1 c.2597delT p.(Leu866fs) Frameshift deletion Class 1 8 55,539,041 A/T - RP1 c.2599A>T p.(Lys867*) Stopgain Class 2 8 55,539,049 G/GA - RP1 c.2613dupA p.(Arg872fs) Frameshift insertion Class 1 8 55,539,439 TG/T - RP1 c.2999delG p.(Gly1000fs) Frameshift deletion Class 2 8 55,540,111 C/A - RP1 c.3669C>A p.(Cys1223*) Stopgain Class 2 8 55,540,637 TG/T rs762951570 RP1 c.4196delG p.(Cys1399fs) Frameshift deletion Class 1 8 55,542,244 A/AT rs868005849 RP1 c.5805dupT p.(Ala1936fs) Frameshift insertion Class 2 8 55,542,620 GA/G rs775367880 RP1 c.6181delA p.(Ile2061fs) Frameshift deletion Class 2 8 55,542,795 G/A rs753732597 RP1 c.6353G>A p.(Ser2118Asn) Missense Class 1 9 32,541,984 G/A rs869312183 TOPORS c.2539C>T p.(Arg847*) Stopgain Class 1 9 32,542,070 G/GT - TOPORS c.2452_2453insA p.(Ser818fs) Frameshift insertion Class 2 9 32,542,101 C/A - TOPORS c.2422G>T p.(Glu808*) Stopgain Class 1 10 48,390,091 C/A rs77257977 RBP3 c.787G>T p.(Ala263Ser) Missense Class 1 10 48,390,433 C/A - RBP3 c.445G>T p.(Glu149*) Stopgain Class 2 11 46,724,300 G/A rs536561101 ZNF408 c.377G>A p.(Ser126Asn) Missense Class 1 11 46,724,745 C/T - ZNF408 c.604C>T p.(Gln202*) Stopgain Class 2 11 46,727,032 G/GC - ZNF408 c.1783dupC p.(Arg595fs) Frameshift insertion Class 2 11 61,724,887 G/A - BEST1 c.665G>A p.(Gly222Glu) Missense Class 1 11 61,725,666 C/T rs372989281 BEST1 c.763C>T p.(Arg255Trp) Missense Class 1 12 110,019,208 C/T rs775474803 MVK c.380C>T p.(Pro127Leu) Missense Class 1 14 24,551,906 G/A - NRL c.152C>T p.(Pro51Leu) Missense Class 1 14 24,551,909 G/A - NRL c.149C>T p.(Ser50Leu) Missense Class 1 14 68,192,801 C/T rs202126574 RDH12 c.377C>T p.(Ala126Val) Missense Class 1 14 68,193,730 C/T rs759408031 RDH12 c.481C>T p.(Arg161Trp) Missense Class 1 14 68,196,003 TC/T - RDH12 c.759delC p.(Phe254fs) Frameshift deletion Class 2 14 68,196,010 T/TA - RDH12 c.761_762insA p.(Phe254fs) Frameshift insertion Class 2 14 88,893,049 G/A rs761981554 SPATA7 c.749+1G>A p.? Canonical splice site variant Class 1 15 72,103,855 G/A rs544807110 NR2E3 c.151G>A p.(Gly51Arg) Missense Class 1 15 72,103,870 G/A rs121912631 NR2E3 c.166G>A p.(Gly56Arg) Missense Class 1 15 72,103,930 C/T rs104894492 NR2E3 c.226C>T p.(Arg76Trp) Missense Class 1 15 72,104,171 G/A rs766096417 NR2E3 c.311G>A p.(Arg104Gln) Missense Class 1 15 72,106,406 C/T - NR2E3 c.1048C>T p.(Gln350*) Stopgain Class 1 15 89,753,595 G/A rs201588178 RLBP1 c.875C>T p.(Thr292Met) Missense Class 1 16 1,573,703 T/G - IFT140 c.3271-2A>C p.? Canonical splice site variant Class 2 16 1,573,885 G/A - IFT140 c.3214C>T p.(Arg1072*) Stopgain Class 2 16 1,574,672 CTGTCTCGT/C - IFT140 c.3014_3021delACGAGACA p.(Asn1005fs) Frameshift deletion Class 2 16 1,575,324 G/C - IFT140 c.2772C>G p.(Tyr924*) Stopgain Class 2 16 1,575,885 CACTA/C rs769075694 IFT140 c.2767_2768+2delTAGT p.(Tyr923fs) Frameshift deletion Class 2 16 1,621,535 CCT/C - IFT140 c.1525-2_1525-1delAG p.? Canonical splice site variant Class 2 16 56,531,779 G/A rs370581600 BBS2 c.1673C>T p.(Thr558Ile) Missense Class 1 16 56,534,887 C/A - BBS2 c.1276G>T p.(Glu426*) Stopgain Class 2 16 56,536,366 G/A rs121908178 BBS2 c.943C>T p.(Arg315Trp) Missense Class 1 16 56,536,711 G/A rs764164384 BBS2 c.814C>T p.(Arg272*) Stopgain Class 1 16 56,539,874 C/T - BBS2 c.792G>A p.(Trp264*) Stopgain Class 2 16 57,279,314 CTT/C rs754087233 ARL2BP c.37_38delTT p.(Phe13fs) Frameshift deletion Class 2 16 57,938,729 C/CT - CNGB1 c.2542_2543insA p.(Gly848fs) Frameshift insertion Class 2 16 57,946,843 T/C rs370288562 CNGB1 c.2360A>G p.(Tyr787Cys) Missense Class 1 16 57,946,899 C/T rs767311166 CNGB1 c.2305-1G>A p.? Canonical splice site variant Class 2 16 57,949,231 CA/C - CNGB1 c.2225delT p.(Leu742fs) Frameshift deletion Class 2 17 1,554,143 G/A - PRPF8 c.6961C>T p.(Gln2321*) Stopgain Class 1 17 1,554,176 T/C - PRPF8 c.6928A>G p.(Arg2310Gly) Missense Class 1 17 1,554,477 G/A - PRPF8 c.6778C>T p.(Gln2260*) Stopgain Class 2 17 1,558,641 CACTT/C - PRPF8 c.5986_5987+2delAAGT p.(Asn1996fs) Frameshift deletion Class 2 17 58,236,783 T/C - CA4 c.937T>C p.(Ter313Argext*?) Stoploss Class 2 17 74,536,225 T/C rs527236092 PRCD c.2T>C p.(Met1?) Missense Class 1 17 74,536,275 C/T rs527451635 PRCD c.52C>T p.(Arg18*) Stopgain Class 1 17 74,536,287 C/T rs387907268 PRCD c.64C>T p.(Arg22*) Stopgain Class 1 17 74,536,298 G/A rs779066277 PRCD c.74+1G>A p.? Canonical splice site variant Class 1 17 79,503,900 G/C - FSCN2 c.1274-1G>C p.? Canonical splice site variant Class 2 19 48,339,520 C/T rs104894672 CRX c.121C>T p.(Arg41Trp) Missense Class 1 19 48,343,051 G/T - CRX c.727G>T p.(Gly243*) Stopgain Class 2 19 54,625,265 G/T - PRPF31 c.265G>T p.(Glu89*) Stopgain Class 2 19 54,625,304 G/T - PRPF31 c.304G>T p.(Glu102*) Stopgain Class 2 19 54,625,310 G/T - PRPF31 c.310G>T p.(Glu104*) Stopgain Class 2 19 54,631,534 T/TG - PRPF31 c.1033dupG p.(Ala345fs) Frameshift insertion Class 2 19 54,631,562 C/T rs868538598 PRPF31 c.1060C>T p.(Arg354*) Stopgain Class 1 19 54,631,746 CG/C - PRPF31 c.1142delG p.(Gly381fs) Frameshift deletion Class 1 19 54,632,439 A/AAG - PRPF31 c.1154_1155insAG p.(Asp386fs) Frameshift insertion Class 2 20 62,626,344 C/T rs369787039 PRPF6 c.514C>T p.(Arg172Trp) Missense Class 1 X 13,785,240 TATTAGG/T rs766872363 OFD1 c.2600-5_2600delATTAGG p.(Ser867fs) Frameshift deletion Class 2 X 38,145,050 T/A - RPGR c.3202A>T p.(Lys1068*) Stopgain Class 2 X 38,145,845 CCT/C rs398122960 RPGR c.2405_2406delAG p.(Glu802fs) Frameshift deletion Class 1 X 38,146,014 TTC/T - RPGR c.2236_2237delGA p.(Glu746fs) Frameshift deletion Class 1 X 38,146,098 GC/G - RPGR c.2153delG p.(Gly718fs) Frameshift deletion Class 1 X 38,146,171 T/TTCTCTCCC - RPGR c.2073_2080dupGGGAGAGA p.(Lys694fs) Frameshift insertion Class 2 X 38,146,249 TG/T - RPGR c.2002delC p.(His668fs) Frameshift deletion Class 1 X 38,147,142 A/AATGCTTCATGC - RPGR c.1724_1725insGCATGAAGCAT p.(Ile576fs) Frameshift insertion Class 2 X 38,147,145 C/CAT - RPGR c.1721_1722insAT p.(Thr575fs) Frameshift insertion Class 2 X 38,147,225 C/A - RPGR c.1642G>T p.(Glu548*) Stopgain Class 2

Koyanagi Y, et al. J Med Genet 2019; 0:662–670. doi: 10.1136/jmedgenet-2018-105691 Supplementary material J Med Genet

X 38,150,217 G/A - RPGR c.1567C>T p.(Gln523*) Stopgain Class 2 X 38,150,223 G/A - RPGR c.1561C>T p.(Gln521*) Stopgain Class 2 X 38,156,645 CAA/C - RPGR c.1304_1305delTT p.(Leu435fs) Frameshift deletion Class 2 X 38,158,377 A/T - RPGR c.1077T>A p.(Cys359*) Stopgain Class 2 X 38,160,626 T/C - RPGR c.935-2A>G p.? Canonical splice site variant Class 1 X 38,163,917 C/T rs62640590 RPGR c.905G>A p.(Cys302Tyr) Missense Class 1 X 38,169,882 G/A - RPGR c.764C>T p.(Thr255Ile) Missense Class 1 X 38,178,160 GAA/G - RPGR c.389_390delTT p.(Phe130fs) Frameshift deletion Class 2 X 38,180,294 G/A - RPGR c.296C>T p.(Thr99Ile) Missense Class 1 X 38,182,652 C/T - RPGR c.154G>A p.(Gly52Arg) Missense Class 1 X 38,186,588 C/T rs62638626 RPGR c.28+5G>A p.? Non-canonical splice site variant Class 1 X 46,696,622 G/A - RP2 c.87G>A p.(Trp29*) Stopgain Class 2 X 46,713,161 G/A rs28933687 RP2 c.353G>A p.(Arg118His) Missense Class 1 X 46,713,481 CG/C - RP2 c.677delG p.(Gly226fs) Frameshift deletion Class 2 * Chromosomes are based on Build37 (hg19). Detected 350 pathogenic variants were shown. Class 1 comprised variants previously reported as pathogenic in the HGMD pro database (2017.2) (variants classified as “DM” and “DM?”) or ClinVar (accessed on October 1, 2017) (variants with ClinVar star 2+ and star 1). Class 2 included putative deleterious variants (nonsense, frameshift, or canonical splice site variants) that were not previously reported. REF, reference allele; ALT, alternative allele.

Koyanagi Y, et al. J Med Genet 2019; 0:662–670. doi: 10.1136/jmedgenet-2018-105691