TABLE 1.
Pathogenic variants detected in patients with high myopia and RRD.
| Gene_Symbol | Type | Sample | Type | Position | Exon | Changes | Frequency | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Nucleotide | Amino_Acid | 1000G | ESP6500 | gnomAD | ExAC | |||||||
| CAPN5 | het | 23C702282 | RetNet | chr11:76829253 | exon8 | 8 | c.1022G > A | p.R341H | — | — | 1.19E-05 | 1.65E-05 |
| COL11A1 | het | 23C702255 | RetNet, Syndromic and RD | chr1:103444283 | exon35 | 35 | c.2735C > T | p.P912L | 7.99E-04 | — | 2.27E-04 | 2.00E-04 |
| COL11A1 | het | 23C702281 | RetNet, Syndromic and RD | chr1:103354445 | exon60 | 60 | c.4495C > T | p.P1499S | 2.00E-04 | — | 1.79E-04 | 9.91E-05 |
| COL2A1 | het | 23C702250 | RetNet, Syndromic and RD | chr12:48378777 | exon26 | 26 | c.1626 + 1G > A | — | — | — | — | — |
| COL2A1 | het | 23C702252 | RetNet, Syndromic and RD | chr12:48380960 | exon20 | 20 | c.1060-1G > C | — | — | — | — | — |
| COL2A1 | het | 23C702270 | RetNet, Syndromic and RD | chr12:48370347 | exon49 | 49 | c.3439C > G | p.P1147A | — | — | 3.98E-06 | 8.25E-06 |
| COL2A1 | het | 23C702287 | RetNet, Syndromic and RD | chr12:48376314 | exon34 | 34 | c.2272G > A | p.A758T | — | — | — | — |
| EFEMP1 | het | 23C702251 | RetNet | chr2:56097872 | exon11 | 11 | c.1303G > A | p.G435R | — | — | 3.99E-06 | — |
| FBN1 | het | 23C702266 | Syndromic and RD | chr15:48760167 | exon38 | 38 | c.4715C > A | p.T1572N | — | — | — | — |
| FZD4 | het | 23C702248 | RetNet and RD | chr11:86662209 | exon2 | 2 | c.1589G > A | p.G530E | 9.98E-04 | — | 1.67E-04 | 2.00E-04 |
| IMPDH1 | het | 23C702283 | RetNet | chr7:128034631 | exon15 | 15 | c.1573G > A | p.A525T | — | — | 3.19E-05 | 8.26E-06 |
| NR2E3 | het | 23C702273 | RetNet | chr15:72110009 | exon9 | 9 | c.1217A > G | p.D406G | — | — | 4.03E-06 | — |
| PDE6B | het | 23C702259 | RetNet | chr4:619752-619752 | exon1 | 1 | c.337_338insTCCTGGAGGCTT | p.V113delinsVLEAL | — | — | — | — |
| RDH12 | het | 23C702258 | RetNet | chr14:68195905 | exon8 | 8 | c.659-3C > G | — | — | — | — | — |
| RP1 | het | 23C702274 | RetNet and Syndromic | chr8:55540769 | exon4 | 4 | c.4327C > T | p.R1443W | — | 7.70E-05 | 5.18E-05 | 6.64E-05 |
| SNRNP200 | het | 23C702271 | RetNet | chr2:96944075 | exon39 | 39 | c.5510A > G | p.N1837S | — | — | 3.98E-06 | - |
| VCAN | het | 23C702263 | RetNet, Syndromic and RD | chr5:82837830 | exon8 | 8 | c.9008C > T | p.T3003M | — | — | 3.21E-05 | 2.48E-05 |
| VCAN | het | 23C702278 | RetNet, Syndromic and RD | chr5:82875868 | exon14 | 14 | c.9950T > C | p.I3317T | — | — | — | — |
| LRP5 | het | 23C702262 | RetNet and RD | chr11:68115614 | exon2 | 2 | c.391C > T | p.R131C | — | 7.70E-05 | 1.59E-05 | 8.29E-06 |
| Prediction | Pathogenic_Analysis (ACMG) | Note | Disease | |||
|---|---|---|---|---|---|---|
| SIFT | PolyPhen_2 | MutationTaster | GERP++ | (PMID) | ||
| T (0.062) | PD (0.984) | DC (1) | C (4.14) | Likely pathogenic (PM1,PM5, PP2, PP3) | Novel | Vitreoretinopathy, neovascular inflammatory |
| D (0.043) | B (0.244) | DC (1) | C (5.35) | Likely pathogenic (PS1, PM2, PP3) | 23967202 | Stickler syndrome |
| D (0.017) | PD (0.999) | DC (1) | C (5.95) | Likely pathogenic (PS2, PM2, PP3) | Novel | Stickler syndrome |
| — | — | DC (1) | C (5.01) | Pathogenic (PVS1, PS1, PM1, PM2, PM4) | 10706362; 25525159; 26747767 | Stickler syndrome |
| — | — | — | — | Pathogenic (PVS1,PS2, PM2,PP3, PP5) | Novel | Stickler syndrome |
| T (0.445) | B (0.023) | DC (1) | C (5.43) | Likely pathogenic (PM2, PM5, PP3) | Novel | Stickler syndrome |
| T (0.061) | B (0.006) | DC (1) | C (5.55) | Likely pathogenic (PM2, PM5, PP3, PP4) | Novel | Stickler syndrome |
| T (0.485) | PD (0.93) | DC (1) | C (4.74) | Likely pathogenic (PS1, PM2, PP3) | 26747767 | Doyne honeycomb degeneration of retina |
| T (1) | B (0) | DC (0.93) | C (5.14) | Likely pathogenic (PM1, PM2, PP2 PP3) | Novel | Marfan syndrome |
| D (0.013) | B (0.078) | DC (1) | C (4.14) | Likely pathogenic (PS1, PM2, PP2 PP3) | 25711638; 30097784;30452590;31237656 | Exudative vitreoretinopathy 1 |
| D (0) | PD (0.798) | DC (1) | C (4.29) | Likely pathogenic (PM1, PM2, PP2, PP3) | Novel | Leber congenital amaurosis 11 |
| — | PD (0.954) | — | C (5.02) | Likely pathogenic (PS1, PM1, PM2,PP2 PP3) | 24891813 | Retinitis pigmentosa 37 |
| — | — | — | — | Likely Pathogenic (PM2, PM4, PP1, PP5) | Novel | Night blindness, congenital stationary, autosomal dominant 2 |
| — | — | — | — | Likely Pathogenic (PM2, PM4, PP1, PP5) | Novel | Leber congenital amaurosis 13 |
| D (0) | PD (0.798) | Polymorphism (0.913) | C (4.32) | Pathogenic (PS1, PM2, PM5, PP1, PP3, PP5) | 23991373; 31054281; 34426522 | Retinitis pigmentosa |
| T (0.496) | B (0.01) | DC (1) | C (5) | Likely Pathogenic (PM1, PM2, PP1, PP2) | Novel | Retinitis pigmentosa 33 |
| T (0.178) | PD (0.706) | DC (1) | C (5.16) | Likely Pathogenic (PM2, PM5, PP2, PP3) | Novel | Wagner syndrome |
| D (0.004) | PD (0.813) | DC (1) | C (6.03) | Likely pathogenic (PM1, PM2, PP2, PP3) | Novel | Wagner syndrome |
| D (0) | PD (0.999) | DC (1) | C (3.71) | Likely pathogenic (PM1, PM2, PP2, PP3) | Novel | Exudative vitreoretinopathy 4 |
Note: P, Pathogenic; LP, Likely pathogenic; U, Uncertain; T, Tolerated; D, Damaging; PB, Probably_D; B, Benign; DC, Disease_causing; C, Conserved; PVS: very strong pathogenic criterion; PS: strong pathogenic criterion; PM: moderate pathogenic criterion; PP, supporting pathogenic criterion.