Table 2 In silico prediction of pathogenic effect of MLL2 missense and splice site variants
From: Mutation spectrum of MLL2 in a cohort of kabuki syndrome patients
| Â | Â | Â | Â | Prediction of damaging effect at the protein level | Â | Â | |||
|---|---|---|---|---|---|---|---|---|---|
ID | Exon | Mutation | AA change | Â | Â | MutPred | Rescue-ESE | Fas-ESS | |
| Â | Â | Â | Â | Polyphen | Align GVGD | Probability of deleterious mutation | Confident in silico hypothesis | Â | Â |
KB32 | 11 | c.3773G>A | p.Arg1258Gln | benign | deleterious | 0.16 | loss of loop (p = 0.0288, loss of catalytic residue at R1258 (p = 0.0301); gain of helix (p = 0.0349) | no change | no change |
KB28 | 15 | c.[4249A>G;4252C>A] | p.[Met1471Val;Leu1418Met] | benign; benign | deleterious; deleterious | 0.46; 0.47 | none; none | no change | gain of one ESS |
KB34 | 16 | c.4565A>G | p.Gln1522Arg | benign | deleterious | 0.50 | none | loss of one ESE | no change |
KB27 | 34 | c.8521C>A | p.Pro2841Thr | possibly damaging | deleterious | 0,24 | gain of phoshorylation P2841 (p = 0.028) | gain of two ESEs | loss of one ESS |
KB38 | 48 | c.[15084C>G;15100T>G] | p.[Asp 5028Glu;Phe5034Val] | benign; benign | deleterious; deleterious | 0.42; 0.56 | none; none | gain of three ESEs | loss of three ESSs |
KB76 | 48 | c.1517A>C | p.His5059pro | benign | deleterious | 0,71 | none | no change | no change |
KB17 | 50 | c.16019G>A | p.Arg5340Gln | benign | deleterious | 0,53 | gain of ubiquitination at K5344 (p = 0.0396) | gain of two ESEs | no change |
ID | Intron | Mutation | Splice site modification prediction | Predicted Protein | Conclusion | ||||
| Â | Â | Â | Â | NetGene | NNSplice | Â | Â | Â | Â |
KB31 | Intron 3-4 | c.400+1G>A | Loss of DS | Loss of DS | 135 AA with novel 2 AA | deleterious | |||
KB20 | Intron 3-4 | c.401-3A>G | New AS at-3 | New AS at-3 | 217 AA with novel 84 AA | deleterious | |||
KB29 | Intron 42-43 | c. 13999+5 G>A | Lower confidence of DS prediction | Lower confidence of DS prediction | Â | unpredictable | |||