Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27916 | 83971;83972;83973 | chr2:178562386;178562385;178562384 | chr2:179427113;179427112;179427111 |
| N2AB | 26275 | 79048;79049;79050 | chr2:178562386;178562385;178562384 | chr2:179427113;179427112;179427111 |
| N2A | 25348 | 76267;76268;76269 | chr2:178562386;178562385;178562384 | chr2:179427113;179427112;179427111 |
| N2B | 18851 | 56776;56777;56778 | chr2:178562386;178562385;178562384 | chr2:179427113;179427112;179427111 |
| Novex-1 | 18976 | 57151;57152;57153 | chr2:178562386;178562385;178562384 | chr2:179427113;179427112;179427111 |
| Novex-2 | 19043 | 57352;57353;57354 | chr2:178562386;178562385;178562384 | chr2:179427113;179427112;179427111 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | None | None | 0.063 | N | 0.319 | 0.125 | 0.445410361449 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| V/I | None | None | 0.063 | N | 0.319 | 0.125 | 0.445410361449 | gnomAD-4.0.0 | 2.05582E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.70027E-06 | 0 | 0 |
| V/L | rs770267115  |
-0.432 | 0.507 | N | 0.455 | 0.226 | 0.552125808554 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| V/L | rs770267115 |
-0.432 | 0.507 | N | 0.455 | 0.226 | 0.552125808554 | gnomAD-4.0.0 | 6.85273E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0009E-07 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.288 | likely_benign | 0.2861 | benign | -1.366 | Destabilizing | 0.301 | N | 0.245 | neutral | N | 0.521057747 | None | None | N |
| V/C | 0.7762 | likely_pathogenic | 0.7751 | pathogenic | -0.757 | Destabilizing | 1.0 | D | 0.622 | neutral | None | None | None | None | N |
| V/D | 0.8046 | likely_pathogenic | 0.7964 | pathogenic | -1.154 | Destabilizing | 0.996 | D | 0.727 | prob.delet. | N | 0.489976338 | None | None | N |
| V/E | 0.6692 | likely_pathogenic | 0.6763 | pathogenic | -1.048 | Destabilizing | 0.983 | D | 0.647 | neutral | None | None | None | None | N |
| V/F | 0.4199 | ambiguous | 0.4236 | ambiguous | -0.817 | Destabilizing | 0.998 | D | 0.627 | neutral | N | 0.476395214 | None | None | N |
| V/G | 0.2869 | likely_benign | 0.2973 | benign | -1.788 | Destabilizing | 0.991 | D | 0.676 | prob.neutral | N | 0.50372278 | None | None | N |
| V/H | 0.8756 | likely_pathogenic | 0.8708 | pathogenic | -1.439 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| V/I | 0.1267 | likely_benign | 0.1355 | benign | -0.262 | Destabilizing | 0.063 | N | 0.319 | neutral | N | 0.48823604 | None | None | N |
| V/K | 0.7859 | likely_pathogenic | 0.7995 | pathogenic | -0.906 | Destabilizing | 0.992 | D | 0.647 | neutral | None | None | None | None | N |
| V/L | 0.4279 | ambiguous | 0.4613 | ambiguous | -0.262 | Destabilizing | 0.507 | D | 0.455 | neutral | N | 0.471533369 | None | None | N |
| V/M | 0.2745 | likely_benign | 0.3035 | benign | -0.239 | Destabilizing | 0.998 | D | 0.545 | neutral | None | None | None | None | N |
| V/N | 0.5779 | likely_pathogenic | 0.5731 | pathogenic | -0.885 | Destabilizing | 0.951 | D | 0.735 | prob.delet. | None | None | None | None | N |
| V/P | 0.9585 | likely_pathogenic | 0.955 | pathogenic | -0.596 | Destabilizing | 0.975 | D | 0.696 | prob.neutral | None | None | None | None | N |
| V/Q | 0.6718 | likely_pathogenic | 0.6634 | pathogenic | -0.885 | Destabilizing | 0.995 | D | 0.697 | prob.neutral | None | None | None | None | N |
| V/R | 0.7795 | likely_pathogenic | 0.7833 | pathogenic | -0.67 | Destabilizing | 0.998 | D | 0.746 | deleterious | None | None | None | None | N |
| V/S | 0.3309 | likely_benign | 0.3122 | benign | -1.506 | Destabilizing | 0.793 | D | 0.43 | neutral | None | None | None | None | N |
| V/T | 0.2269 | likely_benign | 0.2449 | benign | -1.272 | Destabilizing | 0.896 | D | 0.47 | neutral | None | None | None | None | N |
| V/W | 0.9648 | likely_pathogenic | 0.9648 | pathogenic | -1.174 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| V/Y | 0.8526 | likely_pathogenic | 0.8472 | pathogenic | -0.769 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.