Table 3.
Mutations outside the canonical splicing domains in the NF1 gene classified as causative due to effects on in vitro NF1 splicing.
| Inherited | Number found | RNA mutation | DNA mutation | Original classification | Deep intronic | Reported previously |
|---|---|---|---|---|---|---|
| No | 1 | r.100_204del | c.204 + 3_204 + 6delGAGT | splice site | ||
| Yes | 1 | r.288_289ins288 + 1917_288 + 2024 | c.288 + 2025T > G | splice site | Yes | |
| No × 2 | 2 | r.289_479del | c.479 + 5G > A | splice site | ||
| Yes | 1 | r.480_586del | c.586 + 3_586 + 4delinsGG | splice site | ||
| Yes | 1 | r.480_586del | c.586 + 5G > A | splice site | ||
| No | 1 | r.587_654del | c.587-12_587-10delinsGGG | splice site | ||
| Yes | 1 | r.888_889ins888 + 710_888 + 784 | c.888 + 789A > G | splice site | Yes | |
| Yes | 1 | r.1063_1185del | c.1185 + 5G > C | splice site | Yes | |
| Yes × 1 No × 1 |
2 | r.1260_1261ins1260 + 1605_1260 + 1646 | c.1260 + 1604 A > G | splice site | Yes | Yes but missed on DNA |
| Yes × 2 | 2 | r.1393_1527del | c.1527 + 4_1527 + 7delAGTA | splice site | ||
| No | 1 | r.2252_2325del | c.2325 + 3A > G | splice site | ||
| No | 1 | r.2409_2410ins2410–15_2410–1 | c.2410–16A > G | splice site | Yes | |
| Yes | 1 | r.2851_2990del | c.2851–6-2851-3del | splice site | ||
| No | 1 | r.3494_3496dupuag p.(Ile1165_Gly1166insVal) | c.3497-4T > G | splice site | ||
| No | 1 | r.4110_4111 ins4110 + 836_4110 + 940 | c.4110 + 945A > G | splice site | Yes | Yes but missed on DNA |
| No | 1 | r.4514_4515ins17 | c.4515-14T > G | splice site | ||
| Yes | 1 | r.5152_5205del p.(Phe1719_Val1736del) | c.5205 + 3A > T | splice site | ||
| Yes | 2 | r.[5206_5546del; 5206_5749del] | c.5206-38A > G | splice site | Yes | |
| Yes | 1 | r.5749_5750ins5749 + 155_5749 + 331 | c.5749 + 332A > G | splice site | Yes | Yes but missed on DNA |
| No | 1 | r.6085_6364del | c.6364 + 4A > G | splice site | ||
| Yes | 1 | r.[6756_6757ins6757-2_6757–1; 6757_6858del] | c.6757-3A > G | splice site | ||
| No | 1 | r.7907_7908ins7908-391_7908–322 | c.7908-321C > G | splice site | Yes | Yes but missed on DNA |
| No | 1 | r.2952_2990del | c.2953C > T p.(Gln985Ter) | Nonsense | ||
| Yes | 1 | r.5940_5943delgcag | c.5941C > T p.(Gln1981Ter) | Nonsense | ||
| No | 1 | r.6642_6756del | c.6754A > T p.(Lys2252Ter) | Nonsense | ||
| Yes x 1 No x 2 |
3 | r.6757_6858del | c.6792C > A p.(Tyr2264Ter) | Nonsense | Yes | |
| No | 1 | r.6756_6858del | c.6792C > A p.(Tyr2264Ter) | Nonsense | Yes | |
| Yes | 1 | r.7647_7675del29 | c.7648A > T p.(Arg2550Ter) | Nonsense | ||
| Yes | 2 | r.[1229u > a; 1260_1261ins1260 + 1_1260 + 13] | c.1229T > A p.(Leu410Gln) | VUS missense | ||
| No | 1 | r.1722_1748del | c.1748A > G p.(Lys583Arg) | VUS missense | Yes | |
| No | 1 | r.2252_2325del | c.2325G > T p.(Glu775Asp) | VUS missense |
||
| Yes | 1 | r.[5206_5546del; 5206_5749del] | c.5546G > A (p.Arg1849Gln) | VUS missense | ||
| Yes | 1 | r.[5206_5546del; 5206_5749del] | c.5546G > T p.(Arg1849Leu) | VUS Missense |
||
| No | 1 | r.5940_5943delgcag | c.5943G > A p.(Gln1981Gln) | VUS Synonymous | ||
| Total | 41 | 26 Splice 7 VUS 8 Nonsense |
||||
| Additional samples only classifiable by RNA without study criteria or information to determine this | Deep intronic | ||||
|---|---|---|---|---|---|
| 1 | r.655_730del | c.655-17_655-5del13 | Splice site | ||
| 1 | r.[1260 + 1_1260 + 13ins;1260 + 4a > c] | c.1260 + 4A > C | Splice site | ||
| 1 | r.1393_1527del | c.1393-13_1393-3del11 | Splice site | ||
| 1 | r.3494_3496dupuag p.(Ile1165_Gly1166insVal) | c.3497-4T > G | Splice site | ||
| 1 | r.[6642_6858del, 6757_6858del] | c.6757–14T > G | Splice site | ||
| 1 | r.8050_8051ins8050 + 1_8050 + 85 | c.8050 + 86A > G | Splice site | Yes | |
| 1 | r.289_479del | c.479G > T p.(Arg160Met) | VUS missense | ||
| Subtotal | 7 | 6 splice 1 missense | |||
| Previously reported variants outside study criteria and outside canonical domain | |||||
| 1 | r.1642_1721del | c.1721 + 3A > G | Splice site | ||
| 1 | r.4110_4111ins4110 + 4160_4110 + 4239 | c.4110 + 4159A > G | Splice site | Yes | |
| 1 | r.1466_1527del | c.1466 A > G p.(Tyr489Cys) | VUS missense | ||
| 2 | r.1846_1886del41 | c.1885G > A p.(Gly629Arg) | VUS missense | ||
| 1 | r.2252_2325del | c.2325G > T p.(Glu775Asp) | VUS missense | ||
| Total | 13 | 5 missense 8 splice |
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