Table 4.
Bioinformatic analysis of novel missense mutations associated with hypertrophic cardiomyopathy among Egyptian patients
| Gene/mutation in protein level | Grantham difference (0–225) | SIFTb D = deleterious (score < 0.05) T = tolerated (score > 0.05) | Align GVGD classc | Polyphen-2 (score)d | Likelihood of pathogenicitye |
|---|---|---|---|---|---|
| MYBPC3/Val94Ala | 64 | D (0.01) | C25 | Probably damaging (0.999) | Likely |
| MYBPC3/Pro102Leua | 98 | D (0.04) | C0 | Benign (0.008) | Pathogenic |
| MYBPC3/Arg177His | 29 | D (0.01) | C0 | Possibly damaging (0.889) | Likely |
| MYBPC3/Glu319Ala | 107 | T (0.53) | C0 | Benign (0.014) | Uncertain |
| MYBPC3/Thr445Met | 81 | D (0.00) | C65 | Probably damaging (1.000) | Likely |
| MYBPC3/Arg470Pro | 103 | D (0.00) | C65 | Probably damaging (0.999) | Likely |
| MYBPC3/Asn515Asp | 23 | D (0.00) | C15 | Benign (0.040) | Uncertain |
| MYBPC3/Glu832Glya | 98 | D (0.00) | C65 | Probably damaging (1.000) | Pathogenic |
| MYBPC3/Arg845Proa | 103 | D (0.00) | C65 | Probably damaging (1.000) | Pathogenic |
| MYBPC3/Leu993Phe | 22 | D (0.03) | C0 | Probably damaging (0.983) | Likely |
| MYBPC3/Arg1138Cys | 180 | D (0.00) | C65 | Probably damaging (1.000) | Likely |
| MYH7/Glu170Lys | 56 | D (0.00) | C0 | Probably damaging (0.996) | Likely |
| MYH7/Leu267Val | 32 | D (0.00) | C0 | Benign (0.011) | Uncertain |
| MYH7/Asp309Asn | 23 | D (0.00) | C0 | Probably damaging (0.963) | Uncertain |
| MYH7/Glu379Lys | 56 | D (0.00) | C0 | Benign (0.315) | Uncertain |
| MYH7/Asp394Glu | 45 | D (0.00) | C0 | Probably damaging (1.000) | Likely |
| MYH7/Asn471Ser | 46 | D (0.00) | C45 | Benign (0.019) | Likely |
| MYH7/Gln498Arg | 43 | D (0.00) | C35 | Benign (0.370) | Likely |
| MYH7/Gly716Ala | 60 | D (0.00) | C55 | Possibly damaging (0.948) | Likely |
| MYH7/Arg819Gln | 43 | D (0.00) | C35 | Probably damaging (1.000) | Likely |
| MYH7/Glu1056Asp | 45 | D (0.00) | C0 | Probably damaging (0.997) | Likely |
| MYH7/Arg1662His | 29 | D (0.00) | C0 | Benign (0.001) | Uncertain |
| TNNT2/Asn152Tyr | 143 | T (0.06) | C0 | Possibly damaging (0.951) | Likely |
| TNNT2/Asn272Asp | 23 | T (0.32) | C0 | Possibly damaging (0.820) | Uncertain |
| TNNT2/Asn269Lysa | 94 | T (1.00) | C0 | Benign (0.028) | Pathogenic |
| TNNT2/Arg288Leu | 102 | T (1.00) | C0 | Probably damaging (0.972) | Uncertain |
aDe novo concurrent with HCM in more than a single family
bSorting intolerant from tolerant prediction
cScores include GV = 0 (invariable), 0 < GV < 62 = variable conservative, GV > 62 = variable nonconservative
dPolymorphism phenotyping
eLikelihood of pathogenicity based on in silico analysis and de novo concurrence of variant in unrelated HCM cases