Table 1.
In silico analysis of the functional effect of the predicted amino acid exchanges resulting from translational read-through of the p.G3142* nonsense mutation in USH2A. All variants were denoted based on the NCBI reference sequence for USH2A (NM_206933.2; GRCh38). Possible effects of the missense variants due to misincorporation during translational read-through protein function were assessed using the following computational in silico tools: MutationTaster (http://www.mutationtaster.org) [36], SIFT (http://sift.jvic.org) [37]; PolyPhen-2 (http://genetics.bwh.harvard.edu/pph2/), and the integrated software Alamut Genova (http://www.interactive-biosoftware.com) using default settings; gnomAD - Genome Aggregation Database (https://gnomad.broadinstitute.org/gene/ENSG00000042781 for USH2A.
| ALAMUT® | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Codon Position Altered | Possible Mispairing | Amino Acid Substitution | SIFT (0–1) |
Polyphen-2 (0–1) |
phyloP (-19.0;10.9) |
Grantham Dist. (0–215) |
Align GVGD [GV:353.86 - GD:0.00] | SIFT (Score: 0. Median: 3.71) |
MutationTaster (probability 1) | gnomAD |
| UGA | GGA | p.Gly3142Gly (=wildtype) | - | - | - | - | - | - | 0 | |
| CGA AGA |
p.Gly3142Arg | tolerated; 0.18 | probably damaging; 1 | 2.3 | moderate physiocochemical difference between G and R, 125 | Class C0 | deleterious | disease-causing, probability 0.999 | 1 heterozygous in 250,190 alleles | |
| UGA | UUA | p.Gly3142Leu | damaging; 0.01 | probably damaging; 1 | 5.63 | moderate physiocochemical difference between G and L, 138 | Class C0 | deleterious | disease-causing, 0.999 | 0 |
| UCA | p.Gly3142Ser | tolerated; 0.09 | probably damaging; 0.985 | 5.63 | small physiocochemical difference between G and S, 56 | Class C0 | deleterious | disease-causing, 0.999 | 0 | |
| UGA | UGG | p.Gly3142Trp | damaging; 0 | probably damaging; 1 | 0.13 | large physiocochemical difference between G and C, 184 | Class C0 | deleterious | disease-causing, 0.999 | 0 |