Table 4.
Summary of putative pathogenic mutations and their bioinformatics predictions
| Patient | Gene | Exon | Nucleotide Change | Amino Acid Change | Classification | SIFT (score) | PolyPhen-2 (score) | NetGene2 | Human Splicing Finder | NNSPLICE | RESCUE-ESE |
|---|---|---|---|---|---|---|---|---|---|---|---|
| RP-1948 | MYO7A | 7 | c.707T>A | p.Leu236Gln | UV3 | deleterious (0) | probably_damaging (1) | Neutral | Neutral | Neutral | A new ESE site is created |
| RP-807 RP-1924 | MYO7A | 27 | c.3503G>A | p.Arg1168Gln | UV3 | deleterious (0) | probably_damaging (1) | Score for the main donor site decreases from 95 to 75 | Score for the main donor site decreases from 90 to 80 | The main donor site is not recognized | Neutral |
| RP-807 | MYO7A | 40 | c.5516T>C | p.Leu1839Pro | UV3 | deleterious (0) | probably_damaging (1) | Score for the main acceptor site decreases from 80 to 77 | Neutral | Neutral | Neutral |
| RP-1614 | MYO7A | 40 | c.5537C>A | p.Prp1846His | UV3 | deleterious (0.01) | possibly_damaging (0.85) | Score for the main acceptor site decreases from 80 to 77 and one acceptor site is not recognized | Neutral | Neutral | Neutral |
| RP-808 | CDH23 | 10 | c.871G>A | p.Gly291Arg | UV3 | deleterious (0) | probably_damaging (1) | Neutral | Neutral | Neutral | A new ESE site is created |
| RP-1426 | CDH23 | 39 | c.5068-2A>T | c.5068-2A>T | UV4 | --- | --- | The main acceptor site is not recognized | Score for the main acceptor site decreases from 95 to 66 | The main acceptor site is not recognized | --- |
| RP-1781 | CDH23 | 68 | c.9569C>T | p.Ala3190Val | UV3 | deleterious (0) | probably_damaging (1) | Neutral | Neutral | Neutral | Neutral |
| RP-1927 | USH2A | 2 | c.269A>G | p.Tyr90Cys | UV3 | tolerated (0.17) | possibly_damaging (0.796) | Score for acceptor site decreases from 82 to 80 | Neutral | Score for acceptor site decreases from 75 to 69 | A ESE site is not recognized |
| RP-1835 | USH2A | 22 | c.4758+3A>G | c.4758+3A>G | UV3 | --- | --- | The main donor site is not recognized | Neutral | The main donor site decreases from 98 to 73 | --- |
| RP-1960 | USH2A | 25 | c.5167G>C | p.Gly1723Arg | UV3 | deleterious (0) | probably_damaging (0.994) | The main donor site is not recognized | Score for the main donor site decreases from 86 to 75 | The main donor site is not recognized | Neutral |
| RP-1455 | USH2A | 28 | c.5666A>G | p.Asp1889Gly | UV3 | deleterious (0) | probably_damaging (0.982) | The main donor and acceptor sites decrease from 82 to 80 and from 53 to 48 respectively and a new acceptor site is created | Neutral | Neutral | Two ESEs are not recognized |
| RP-1496 | GPR98 | 19 | c.3443G>A | p.Gly1148Asp | UV3 | deleterious (0) | probably_damaging (0.999) | Neutral | Neutral | Neutral | Neutral |
| RP-1929 | GPR98 | 58 | c.11974G>A | p.Asp3992Asn | UV3 | deleterious (0.01) | probably_damaging (0.999) | Neutral | Neutral | Neutral | A ESE is not recognized |
| RP-1950 | GPR98 | 70 | c.14278C>T | p.Pro4760Ser | UV3 | deleterious (0) | probably_damaging (0.998) | Neutral | Neutral | Neutral | Neutral |
| RP-1923 | DFNB31 | 9 | c.2234G>A | p.Arg745His | UV3 | deleterious(0.01) | probably_damaging (0.984) | Neutral | Neutral | The main donor site increases from 66 to 86 | Neutral |
SIFT: SIFT Score ranges from 0 to 1. The amino acid substitution is predicted to be damaging if the score is < 0.05, and tolerated if the score is > 0.05.
PolyPhen stablish three classifications: “Probably damaging” (it is believed most likely to affect protein function or structure), “Possibly damaging” (it is believed to affect protein function or structure), “Benign” (most likely lacking any phenotypic effect).
ESE: Exonic Splicing Enhancer.