Table 1 Cases with VUS and phenotype correlation.
ID | Age | Gender | AO | FamHx | Clinical diagnosis | Proband case | Final result | Gene | Transcript | Inh. pattern | Allele 1 | Allele 2 | Allele Segreg. | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
cDNA | protein | variant ACMG classification | Criteria applied for VUS reassessment and reclassification | cDNA | protein | variant ACMG classification | Criteria applied for VUS reassessment and reclassification | ||||||||||||
P377 | 62 | M | 50 | Yes | Best macular dystrophy | Yes | Resolved | BEST1 | NM_004183.4 | AD | c.35C>A | p.(Ala12Asp) | LP | PM2_sup, PP3_mod, PM1_mod, PP2_sup | – | ||||
P378 | 67 | F | 5 | Yes | Usher syndrome | Yes | Resolved | CDH23 | NM_022124.6 | AR | c.7199C>T | p.(Pro2400Leu) | LP | PM2_sup, PM3_strong, PP3_sup | c.7221C>A | p.(Tyr2407*) | P | trans | |
P379 | 25 | F | 21 | No | Nonsyndromic retinitis pigmentosa | Yes | Resolved | CNGA1 | NM_001379270.1 | AR | c.1448T>G | p.(Leu483Arg) | LP | PM2_sup, PP3_strong, PM3_mod | c.82C>T | p.(Arg28*) | P | trans | |
P380 | 71 | F | 10 | Yes | Nonsyndromic retinitis pigmentosa | Yes | Resolved | CNGB1 | NM_001297.5 | AR | c.1644-3C>G | p.(?) | LP | PM2_sup, PP3_sup, PM3_mod, PP1_strong | c.2868_2869insTA | p.(Val957*) | LP | trans | |
P381 | 52 | F | 21 | Yes | Nonsyndromic retinitis pigmentosa | Yes | Resolved | CNGB1 | NM_001297.5 | AR | c.1644-3C>G | p.(?) | LP | PM2_sup, PP3_sup, PM3_mod, PP1_strong | c.2293C>T | p.(Arg765Cys) | LP | trans | |
P382 | 73 | F | 30 | Yes | Stargardt disease | Yes | Resolved | CRB1 | NM_201253.3 | AR | c.4154A>C | p.(Glu1385Ala) | LP | PM2_sup,PM3_mod, PP1_mod, PP3_sup | c.498_506del | p.(Ile167_Gly169del) | P | trans | |
P383 | 70 | F | 35 | Yes | Stargardt disease | No | Resolved | CRB1 | NM_201253.3 | AR | c.4154A>C | p.(Glu1385Ala) | LP | PM2_sup, PM3_mod, PP1_mod, PP3_sup | c.498_506del | p.(Ile167_Gly169del) | P | trans | |
P384 | 49 | F | 43 | No | Maculopathy | Yes | Resolved | CRB1 | NM_201253.3 | AR | c.1760G>A | p.Cys587Tyr | LP | PM2_sup, PP3_sup, PM3_strong | c.613_619del | p.(Ile205Aspfs*13) | P | trans | |
P385 | 18 | M | 4 | No | Cone-rod dystrophy | Yes | Resolved | GUCY2D | NM_000180.3 | AD | c.543G>A | p.(Trp181*) | LP | PM2_sup, PVS1_very strong | - | ||||
P386 | 56 | F | 1 | Yes | Leber congenital amaurosis | Yes | Resolved | KCNJ13 | NM_002242.4 | AR | c.859T>C | p.(Ser287Pro) | LP | PM2_sup, PP1_mod, PP3_strong | c.859T>C | p.(Ser287Pro) | LP | trans | |
P387 | 55 | F | 1 | Yes | Leber congenital amaurosis | No | Resolved | KCNJ13 | NM_002242.4 | AR | c.859T>C | p.(Ser287Pro) | LP | PM2_sup, PP1_mod, PP3_strong | c.859T>C | p.(Ser287Pro) | LP | trans | |
P388 | 39 | F | 5 | No | Albinism | Yes | Resolved | OCA2/TYR | NM_000275.2/NM_000372.4 | digenic | c.1327G>A | p.(Val443Ile) | P | PM3_very strong, PP4_mod, PS3_sup | c.1205G>A | p.(Arg402Gln) | Polymorphism | Not available | |
P389 | 54 | F | 33 | Yes | Nonsyndromic retinitis pigmentosa | Yes | Resolved | PCARE | NM_001029883.3 | AR | c.2677C>T | p.(Pro893Ser) | LP | PM2_sup, PM3_strong, PP1_mod | c.2950C>T | p.(Arg984*) | P | trans | |
P390 | 48 | F | 14 | Yes | Nonsyndromic retinitis pigmentosa | No | Resolved | PCARE | NM_001029883.3 | AR | c.2677C>T | p.(Pro893Ser) | LP | PM2_sup, PM3_strong, PP1_mod | c.2950C>T | p.(Arg984*) | P | trans | |
P391 | 73 | F | 35 | Yes | Nonsyndromic retinitis pigmentosa | Yes | Resolved | PDE6A | NM_000440.2 | AR | c.1065+1G>T | p.(?) | P | PM2_sup, PVS1, PM3_mod | c.1957C>T | p.(Arg653*) | P | trans | |
P392 | 56 | M | 50 | No | Nonsyndromic retinitis pigmentosa | Yes | Resolved | POMGNT1 | NM_017739.4 | AR | c.629G>T | p.(Trp210Leu) | LP | PM2_sup, PP3_mod, PM5_mod, PM3_sup | c.860T>G | p.(Ile287Ser) | P | trans | |
P393 | 59 | M | 55 | Yes | Maculopathy | Yes | Resolved | RDH5 | NM_002905.5 | AD | c.592del | p.(Ile198Tyrfs*15) | LP | PM2_sup, PVS1_very strong | - | ||||
P394 | 59 | M | 22 | Yes | Nonsyndromic retinitis pigmentosa | Yes | Resolved | REEP6 | NM_138393.4 | AR | c.349-4G>T | p.(Cys117Argfs*59) | LP | PM2_sup, PVS1_very strong | c.349-1G>A | p.(Cys117Argfs*59) | P | trans | |
P395 | 52 | F | 1 | No | Leber congenital amaurosis | Yes | Partially resolved | AIPL1 | NM_014336.4 | AR | c.767T>G | p.(Ile256Ser) | VUS | PM2_sup, PP3_sup, PM3_mod | c.767T>G | p.(Ile256Ser) | VUS | PM2_sup, PP3_sup, PM3_mod | trans |
P396 | 59 | M | 50 | No | Best macular dystrophy | Yes | Partially resolved | BEST1 | NM_004183.4 | AD | c.847T>C | p.(Phe283Leu) | VUS | PM2_sup, PP3_mod, PM1_mod | ND | ||||
P397 | 32 | M | 5 | No | Usher syndrome | Yes | Partially resolved | CDH23 | NM_022124.6 | AR | c.8699A>G | p.(Asp2900Gly) | VUS | PM2_sup, BP4_sup, PM3_mod | c.289-1_304del | p.(?) | LP | trans | |
P398 | 57 | M | 45 | No | Cone-rod dystrophy | Yes | Partially resolved | CDHR1 | NM_033100.4 | AR | c.151G>A | p.(Gly51Ser) | VUS | PM2_sup, PP3_sup, PM3_mod | c.2522_2528del | p.(Ile841Serfs*119) | LP | trans | |
P399 | 87 | F | 50 | No | Cone-rod dystrophy | Yes | Partially resolved | CDHR1 | NM_033100.4 | AR | c.1367C>A | p.(Ala456Glu) | VUS | PM2_sup, PP3_strong | c.1485+2T>G | p.(?) | P | trans | |
P400 | 52 | F | 10 | No | Cone-rod dystrophy | Yes | Partially resolved | CDHR1 | NM_033100.4 | AR | c.1367C>A | p.(Ala456Glu) | VUS | PM2_sup, PP3_strong | c.1367C>A | p.(Ala456Glu) | VUS | PM2_sup, PP3_strong | trans |
P401 | 77 | F | 40 | No | Cone-rod dystrophy | Yes | Partially resolved | CFAP410 | NM_004928.2 | AR | c.140T>C | p.(Leu47Pro) | VUS | PM2_sup | c.140T>C | p.(Leu47Pro) | VUS | PM2_sup | trans |
P402 | 79 | F | 20 | No | Nonsyndromic retinitis pigmentosa | Yes | Partially resolved | CNGB1 | NM_001297.5 | AR | c.2095G>A | p.(Asp699Asn) | VUS | PM2_sup | c.2095G>A | p.(Asp699Asn) | VUS | PM2_sup | trans |
P403 | 71 | M | 65 | No | Nonsyndromic retinitis pigmentosa | Yes | Partially resolved | EYS | NM_001142800.2 | AR | c.8627G>T | p.(Gly2876Val) | VUS | PM2_sup | c.8143C>T | p.(Arg2715*) | P | trans | |
P404 | 84 | M | 50 | No | Nonsyndromic retinitis pigmentosa | Yes | Partially resolved | FSCN2 | NM_001077182.3 | AD | c.1444del | p.(Arg482Alafs) | VUS | PM2_sup, PM4_mod | - | ||||
P405 | 47 | M | 10 | No | Leber congenital amaurosis | Yes | Partially resolved | GUCY2D | NM_000180.4 | AR | c.736A>C | p.(Met246Leu) | VUS | PM2_sup, PM1_mod, PM3_sup | c.3025A>C | p.(Met1009Leu) | P | trans | |
P406 | 26 | M | 20 | No | Familial exudative vitreoretinopathy | Yes | Partially resolved | LRP5 | NM_002335.4 | AD | c.3220G>T | p.(Val1074Phe) | VUS | PM2_sup, PP3_mod, PP1_sup | ND | ||||
P407 | 20 | M | 15 | Yes | Familial exudative vitreoretinopathy | No | Partially resolved | LRP5 | NM_002335.4 | AD | c.3220G>T | p.(Val1074Phe) | VUS | PM2_sup, PP3_mod, PP1_sup | ND | ||||
P408 | 63 | M | 40 | Yes | Nonsyndromic retinitis pigmentosa | Yes | Partially resolved | MERTK | NM_006343.3 | AR | c.950G>A | p.(Cys317Tyr) | VUS | PM2_sup | c.2215_2216del | p.(Val739Cysfs*7) | P | trans | |
P409 | 34 | M | 10 | No | Usher syndrome | Yes | Partially resolved | MYO7A | NM_000260.4 | AR | c.5537C>A | p.(Pro1846His) | VUS | PM2_sup, PP3_sup, PM3_mod | c.6025del | p.(Ala2009Profs*32) | P | trans | |
P410 | 72 | F | unknown | No | Nonsyndromic retinitis pigmentosa | Yes | Partially resolved | PDE6B | NM_000283.4 | AR | c.1148T>A | p.(Val383Glu) | VUS | PM2_sup, PP3_mod, PM3_sup | c.299G>A | p.(Arg100His) | LP | trans | |
P411 | 50 | F | 4 | No | Nonsyndromic retinitis pigmentosa | Yes | Partially resolved | PDE6B | NM_000283.4 | AR | c.2176T>G | p.(Trp726Gly) | VUS | PM2_sup, PP3_sup | c.1879C>G | p.(Arg627Gly) | VUS | PM2_sup, PP3_sup | trans |
P412 | 25 | M | 3 | No | Achromatopsia | Yes | Partially resolved | PDE6C | NM_006204.4 | AR | c.1950C>A | p.(Phe650Leu) | VUS | PM2_sup, PP3_sup | c.712C>T | p.(Arg238*) | P | trans | |
P413 | 46 | F | 16 | No | Fundus albipunctatus | Yes | Partially resolved | RDH5 | NM_002905.5 | AD/AR | c.463C>T | p.(Arg155Trp) | VUS | PM2_sup, PP4_sup | c.779A>C | p.(Asp260Ala) | VUS | PM1_sup, PM2_sup, PP3_sup, PP4_sup | ND |
P414 | 40 | F | 17 | Yes | Nonsyndromic retinitis pigmentosa | Yes | Partially resolved | USH2A | NM_206933.4 | AR | c.12403T>C | p.(Cys4135Arg) | VUS | PM2_sup, PM3_sup | c.2276G>T | p.(Cys759Phe) | P | ND | |
P415 | 88 | F | 70 | No | Nonsyndromic retinitis pigmentosa | Yes | Partially resolved | USH2A | NM_206933.4 | AR | c.7951A>G | p.(Asn2651Asp) | VUS | PM2_sup, BP4_sup, PM3_mod | c.2276G>T | p.(Cys759Phe) | P | trans | |
P416 | 67 | F | 35 | Yes | Usher syndrome | Yes | Partially resolved | USH2A | NM_206933.4 | AR | c.1106T>A | p.(Val369Glu) | VUS | PM2_sup, PP3_sup, PS4_sup, PM3_sup | c.12575G>A | p.(Arg4192His) | LP | trans | |
P417 | 62 | M | 58 | No | Nonsyndromic retinitis pigmentosa | Yes | Partially resolved | ZNF408 | NM_024741.3 | AR | c.1342C>T | p.(Arg448Cys) | VUS | PM2_sup, BP4_mod, PM3_mod | c.1342C>T | p.(Arg448Cys) | VUS | PM2_sup, BP4_mod, PM3_mod | ND |
