TABLE 1.
46 likely pathogenic variants in RPGR from 62 unrelated families (based on NM_001034853).
| Variants | Exon | Nucleotide | Effect | Polyphen2 | PROVEAN | REVEL | CADD | BDGP | HSF | No. of probands | Initial diagnosis | HGMD | Novel or | Evidence |
| change | HVAR | pred | score | (reported)∮ | Known | |||||||||
| Missense and In-frame | ||||||||||||||
| 1 | 2 | c.124T>C | p.Cys42Arg | D | D | 0.897 | 25.7 | / | / | 1 | HM | NA | Novel | 2, 3, 4, 5, 6 |
| 2 | 2 | c.149T>G | p.Val50Gly | D | D | 0.796 | 23.2 | / | / | 1 | RP | NA | Novel | 2, 3, 4, 5, 6 |
| 3 | 4 | c.292C>A | p.His98Asn | D | D | 0.84 | 26.6 | / | / | 1 | CORD | NA | Novel | 1, 2, 3, 4, 5, 6 |
| 4 | 5 | c.431A>G | p.Gln144Arg | D | D | 0.507 | 24.6 | / | / | 1(1) | RP | DM | Known | 2, 3, 4, 5, 6 |
| 5 | 6 | c.494G>T | p.Gly165Val | D | D | 0.982 | 26.6 | / | / | 1 | RP | DM | Known | 1, 2, 3, 4, 5, 6 |
| 6 | 7 | c.748T>C | p.Cys250Arg | D | D | 0.906 | 24.5 | / | / | 1 | RP | DM | Known | 2, 3, 4, 5, 6, 7 |
| 7 | 8 | c.878G>T | p.Arg293Met | D | D | 0.295 | 13.92 | / | / | 1 | RP | NA | Novel | 2, 3, 4, 5, 6, |
| 8 | 8 | c.905G>A | p.Cys302Tyr | D | D | 0.919 | 25.2 | / | / | 1 | RP | DM | Known | 2, 3, 4, 5, 6, |
| 9 | 9 | c.958G>A | p.Gly320Arg | D | D | 0.959 | 32 | / | / | 1 | RP | DM | Known | 2, 3, 4, 5, 6, |
| 10 | 10 | c.1071_1073 delTGG | p.Gly358del | / | / | / | / | / | / | 1(1) | RP | DM? | Known | 1, 2, 4, 5, 6, |
| Truncation | ||||||||||||||
| 1 | 2 | c.140_144dup CTGCT | p.Ser47Phefs*23 | / | / | / | / | / | / | 1(1) | RP | NA | Known | 1, 2, 4, 5, 6 |
| 2 | 6 | c.473del | p.Asp158Glufs*17 | / | / | / | / | / | / | 1(1) | RP | NA | Known | 2, 4, 5, 6 |
| 3 | 6 | c.530dupT | p.Ser178Lysfs*2 | / | / | / | / | / | / | 1(1) | RP | DM | Known | 1, 2, 4, 5, 6 |
| 4 | 10 | c.1243_1244del | p.Arg415Glyfs*37 | / | / | / | / | / | / | 1 | RP | DM | Known | 2, 4, 5, 6 |
| 5 | 14 | c.1685_1686del | p.His562Argfs*20 | / | / | / | / | / | / | 1(1) | RP | DM | Known | 1, 2, 4, 5, 6 |
| 6 | ORF15 | c.1872_1873del | p.Glu624Aspfs*5 | / | / | / | / | / | / | 1 | RP | NA | Known | 1, 2, 4, 5, 6 |
| 7 | ORF15 | c.2075dupG | p.Glu693Argfs*77 | / | / | / | / | / | / | 1(1) | RP | NA | Known | 2, 4, 5, 6 |
| 8 | ORF15 | c.2190del | p.Glu732Argfs*83 | / | / | / | / | / | / | 1 | RP | NA | Novel | 1, 2, 4, 5, 6 |
| 9 | ORF15 | c.2236_2237del | p.Glu746Argfs*23 | / | / | / | / | / | / | 6(2) | RP | NA | Known | 1, 2, 4, 5, 6 |
| 10 | ORF15 | c.2272del | p.Glu758Lysfs*57 | / | / | / | / | / | / | 1 | RP | NA | Novel | 1, 2, 4, 5, 6 |
| 11 | ORF15 | c.2384del | p.Glu795Glyfs*20 | / | / | / | / | / | / | 1 | RP | NA | Known | 2, 4, 5, 6 |
| 12 | ORF15 | c.2403_2406del | p.Glu802Glyfs*12 | / | / | / | / | / | / | 1(1) | RP | NA | Known | 2, 4, 5, 6 |
| 13 | ORF15 | c.2405_2406del | p.Glu802Glyfs*32 | / | / | / | / | / | / | 5(4) | HM, RP | NA | Known | 1, 2, 4, 5, 6 |
| 14 | ORF15 | c.2420_2435del | p.Glu807Glyfs*3 | / | / | / | / | / | / | 1(1) | RP | NA | Known | 2, 4, 5, 6 |
| 15 | ORF15 | c.2442_2445del | p.Gly817Lysfs*2 | / | / | / | / | / | / | 2 | MD, RP | NA | Known | 2, 4, 5, 6 |
| 16 | ORF15 | c.2476_2477del | p.Arg826Glyfs*8 | / | / | / | / | / | / | 2(2) | HM, RP | NA | Known | 1, 2, 4, 5, 6 |
| 17 | ORF15 | c.3027_3028del | p.Glu1010Glyfs*68 | / | / | / | / | / | / | 3(1) | HM, RP | NA | Known | 1, 2, 4, 5, 6 |
| 18 | ORF15 | c.3092del | p.Glu1031Glyfs*58 | / | / | / | / | / | / | 1 | HM | NA | Known | 1, 2, 4, 5, 6 |
| 19 | ORF15 | c.3096_3097del | p.Glu1033Argfs*45 | / | / | / | / | / | / | 2 | HM | NA | Known | 1, 2, 4, 5, 6 |
| 20 | ORF15 | c.3241del | p.Asp1081Metfs*8 | / | / | / | / | / | / | 1(1) | HM | NA | Known | 1, 2, 4, 5, 6 |
| 21 | ORF15 | c.3317del | p.Lys1106Serfs*25 | / | / | / | / | / | / | 1 | RP | NA | Known | 2, 4, 5, 6 |
| 22 | ORF15 | c.3364del | p.Met1122Cysfs*9 | / | / | / | / | / | / | 1(1) | HM | NA | Known | 1, 2, 4, 5, 6 |
| 23 | 2 | c.93G>A | p.Trp31* | / | / | / | 33 | / | / | 1 | RP | DM? | Known | 1, 2, 4, 5, 6 |
| 24 | 2 | c.122C>G | p.Ser41* | / | / | / | 35 | / | / | 1(1) | RP | DM | Known | 1, 2, 4, 5, 6 |
| 25 | 3 | c.191G>A | p.Trp64* | / | / | / | 39 | / | / | 1 | RP | NA | Novel | 2, 4, 5, 6 |
| 26 | 5 | c.352C>T | p.Gln118* | / | / | / | 33 | / | / | 2(1) | RP | DM | Known | 1, 2, 4, 5, 6, 7 |
| 27 | 10 | c.1234C>T | p.Arg412* | / | / | / | 34 | / | / | 2(1) | RP | DM | Known | 1, 2, 4, 5, 6 |
| 28 | 11 | c.1345C>T | p.Arg449* | / | / | / | 23.7 | / | / | 1 | RP | DM | Known | 1, 2, 4, 5, 6 |
| 29 | 13 | c.1561C>T | p.Gln521* | / | / | / | 35 | / | / | 1 | RP | NA | Known | 1, 2, 4, 5, 6 |
| 30 | ORF15 | c.2248G>T | p.Glu750* | / | / | / | 24.9 | / | / | 1 | RP | NA | Novel | 2, 4, 5, 6 |
| 31 | ORF15 | c.2491G>T | p.Glu831* | / | / | / | 32 | / | / | 1 | RP | NA | Known | 2, 4, 5, 6 |
| 32 | IVS4 | c.310 + 1G>A | / | / | / | / | 33 | SD | SD | 1(1) | RP | DM | Known | 2, 4, 5, 6 |
| 33 | IVS9 | c.1060−1G>A | / | / | / | / | 33 | SA | SA | 1 | RP | NA | Novel | 2, 4, 5, 6 |
| 34 | IVS12 | c.1506 + 1G>T | / | / | / | / | 33 | SD | SD | 1 | HM | NA | Novel | 2, 4, 5, 6 |
| 35 | IVS12 | c.1506 + 2T>C | / | / | / | / | 32 | SD | SD | 1 | RP | NA | Novel | 2, 4, 5, 6 |
| 36 | IVS13 | c.1573−2A>G | / | / | / | / | 28.2 | NSC | SA | 1 | RP | DM | Known | 2, 4, 5, 6 |
CORD, cone-rod dystrophy; DM, disease-causing mutations; HM, high myopia; MD, macular degeneration; NA, not available; NSC, no splicing change; RP, retinitis pigmentosa; SA, splicing acceptor; SD, splicing donor; *, termination codon; /, not applicable. BDGP, Berkeley Drosophila Genome Project; HGMD, the Human Gene Mutation Database; HSF, Human Splicing Finder; ()∮ : Previously reported by our lab. None of the variants were recorded in gnomAD except c.3027_3028delGG. Evidence that variant is likely pathogenic: 1 = segregate with inherited eye diseases in one or more families (males with variants were affected); 2 = variants identified in one or more families with eye disease accompany with RP, CORD, COD, MD, or HM; 3 = at least three of four predicting tools are pathogenic; 4 = MAF ≤ 4.7 × 10–5 or absence in gnomAD database; 5 = other known IRD pathogenic variants were not identified; 6 = variants does not find in controls; 7 = variants are de novel.