Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20252 | 60979;60980;60981 | chr2:178590971;178590970;178590969 | chr2:179455698;179455697;179455696 |
| N2AB | 18611 | 56056;56057;56058 | chr2:178590971;178590970;178590969 | chr2:179455698;179455697;179455696 |
| N2A | 17684 | 53275;53276;53277 | chr2:178590971;178590970;178590969 | chr2:179455698;179455697;179455696 |
| N2B | 11187 | 33784;33785;33786 | chr2:178590971;178590970;178590969 | chr2:179455698;179455697;179455696 |
| Novex-1 | 11312 | 34159;34160;34161 | chr2:178590971;178590970;178590969 | chr2:179455698;179455697;179455696 |
| Novex-2 | 11379 | 34360;34361;34362 | chr2:178590971;178590970;178590969 | chr2:179455698;179455697;179455696 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/K | rs752999797  |
-0.137 | 0.055 | N | 0.541 | 0.267 | 0.673631802511 | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 7.99E-05 | 0 | 0 |
| I/K | rs752999797 |
-0.137 | 0.055 | N | 0.541 | 0.267 | 0.673631802511 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 0 | 0 | 0 |
| I/K | rs752999797 |
-0.137 | 0.055 | N | 0.541 | 0.267 | 0.673631802511 | gnomAD-4.0.0 | 1.23965E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.1249E-05 | 0 | 0 | 0 | 0 |
| I/R | None | None | 0.171 | N | 0.587 | 0.375 | 0.705029066125 | gnomAD-4.0.0 | 2.05299E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69885E-06 | 0 | 0 |
| I/T | rs752999797 |
-0.478 | 0.055 | N | 0.413 | 0.244 | 0.459729313489 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| I/T | rs752999797 |
-0.478 | 0.055 | N | 0.413 | 0.244 | 0.459729313489 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs752999797 |
-0.478 | 0.055 | N | 0.413 | 0.244 | 0.459729313489 | gnomAD-4.0.0 | 6.81809E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32538E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2827 | likely_benign | 0.3288 | benign | -0.594 | Destabilizing | 0.016 | N | 0.45 | neutral | None | None | None | None | I |
| I/C | 0.6161 | likely_pathogenic | 0.635 | pathogenic | -0.772 | Destabilizing | 0.628 | D | 0.482 | neutral | None | None | None | None | I |
| I/D | 0.8275 | likely_pathogenic | 0.8433 | pathogenic | -0.257 | Destabilizing | 0.356 | N | 0.593 | neutral | None | None | None | None | I |
| I/E | 0.6916 | likely_pathogenic | 0.7353 | pathogenic | -0.35 | Destabilizing | 0.136 | N | 0.572 | neutral | None | None | None | None | I |
| I/F | 0.101 | likely_benign | 0.1066 | benign | -0.596 | Destabilizing | 0.072 | N | 0.292 | neutral | None | None | None | None | I |
| I/G | 0.7346 | likely_pathogenic | 0.7715 | pathogenic | -0.737 | Destabilizing | 0.072 | N | 0.598 | neutral | None | None | None | None | I |
| I/H | 0.5157 | ambiguous | 0.5393 | ambiguous | 0.053 | Stabilizing | 0.864 | D | 0.577 | neutral | None | None | None | None | I |
| I/K | 0.6013 | likely_pathogenic | 0.6408 | pathogenic | -0.397 | Destabilizing | 0.055 | N | 0.541 | neutral | N | 0.491022842 | None | None | I |
| I/L | 0.0878 | likely_benign | 0.0916 | benign | -0.34 | Destabilizing | 0.001 | N | 0.221 | neutral | N | 0.489428118 | None | None | I |
| I/M | 0.0516 | likely_benign | 0.0547 | benign | -0.489 | Destabilizing | None | N | 0.161 | neutral | N | 0.459337285 | None | None | I |
| I/N | 0.378 | ambiguous | 0.3947 | ambiguous | -0.282 | Destabilizing | 0.356 | N | 0.595 | neutral | None | None | None | None | I |
| I/P | 0.912 | likely_pathogenic | 0.9215 | pathogenic | -0.392 | Destabilizing | 0.628 | D | 0.595 | neutral | None | None | None | None | I |
| I/Q | 0.4803 | ambiguous | 0.5261 | ambiguous | -0.502 | Destabilizing | 0.214 | N | 0.586 | neutral | None | None | None | None | I |
| I/R | 0.4289 | ambiguous | 0.472 | ambiguous | 0.183 | Stabilizing | 0.171 | N | 0.587 | neutral | N | 0.472823589 | None | None | I |
| I/S | 0.3417 | ambiguous | 0.3677 | ambiguous | -0.711 | Destabilizing | 0.072 | N | 0.523 | neutral | None | None | None | None | I |
| I/T | 0.1907 | likely_benign | 0.2016 | benign | -0.697 | Destabilizing | 0.055 | N | 0.413 | neutral | N | 0.518710875 | None | None | I |
| I/V | 0.082 | likely_benign | 0.0838 | benign | -0.392 | Destabilizing | 0.002 | N | 0.311 | neutral | N | 0.456083549 | None | None | I |
| I/W | 0.5515 | ambiguous | 0.5564 | ambiguous | -0.596 | Destabilizing | 0.864 | D | 0.573 | neutral | None | None | None | None | I |
| I/Y | 0.3164 | likely_benign | 0.3338 | benign | -0.363 | Destabilizing | 0.356 | N | 0.501 | neutral | None | None | None | None | I |
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.