Table 3. Pathogenicity clues of the missense variant found in USH2A gene in this study.
| DNA Level (cDNA) Protein Level (p.) | Conserved nucleotide (phyloP: −14.1;6.4) | Physico chemical difference Grantham [0–215] | Variation is in protein domain | Align GVGD | SIFT | Mutation Taster |
|---|---|---|---|---|---|---|
|
c.1729T>C (p.Cys577Arg) |
Moderately
(phyloP: 3.92) |
Large
(Grantham
dist.: 180) |
EGF-like,
laminin |
C65
(GV:0.00 –
GD: 179.53) |
Deleterious
(score: 0,
median: 3.85) |
disease causing
(p value: 1) |
|
c.4144T>C (p.Trp1382Arg) |
Moderately
(phyloP: 3.76) |
Moderate
(Grantham
dist.: 101) |
Fibronectin,
type III |
C0
(GV:268.54 –
GD: 82.54) |
Deleterious
(score: 0,
median: 3.83) |
disease causing
(p value: 1) |
|
c.11831C>A p.Ala3944Asp |
Highly
(phyloP: 5.61) |
Moderate
(Grantham
dist.: 126) |
Fibronectin,
type III |
C65
(GV:0.00 –
GD: 125.75) |
Deleterious
(score: 0,
median: 3.85) |
disease causing
(p value: 1) |
|
c.1040A>G
(p.Asp347Gly) |
Moderately
(phyloP: 3.35) |
Moderate
(Grantham
dist.: 94) |
Laminin,
N-terminal |
GVGD: C0
(GV:213.16 –
GD: 64.73) |
Deleterious
(score: 0,
median: 3.85) |
disease causing
(p value: 1) |
| c.7246A>G (p:Asn2416Asp) | Moderately (phyloP: 3.68) | Small (Grantham dist.: 23) | Fibronectin, type III | C0 (GV:213.69 – GD: 22.66) | Deleterious (score: 0, median: 3.85) | disease causing (p value: 1) |
All sequence variants highly conserved the amino acid, up to Chicken (considering 10 species). Align-GVGD: a grade of C0-C65 is given where C0 is benign and C65 is most likely pathogenic. SIFT (Sort Intolerant From Tolerant,) 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/>0.05. Mutation Tester: A prediction is given as either ‘disease-causing’ or ‘polymorphism’ along with a p value indicating the security of the prediction (with 1 being most secure). PolyPhen (polymorphism phenotyping): “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). c.9959–1G>C, predicted change at acceptor site 1 bps downstream: −100.0% (MaxEnt: −100.0%, NNSPLICE: −100.0%, HSF: −100.0%). The consequence of this change is not predictable, but a skip of exon 51 is very likely.