Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26229 | 78910;78911;78912 | chr2:178567447;178567446;178567445 | chr2:179432174;179432173;179432172 |
| N2AB | 24588 | 73987;73988;73989 | chr2:178567447;178567446;178567445 | chr2:179432174;179432173;179432172 |
| N2A | 23661 | 71206;71207;71208 | chr2:178567447;178567446;178567445 | chr2:179432174;179432173;179432172 |
| N2B | 17164 | 51715;51716;51717 | chr2:178567447;178567446;178567445 | chr2:179432174;179432173;179432172 |
| Novex-1 | 17289 | 52090;52091;52092 | chr2:178567447;178567446;178567445 | chr2:179432174;179432173;179432172 |
| Novex-2 | 17356 | 52291;52292;52293 | chr2:178567447;178567446;178567445 | chr2:179432174;179432173;179432172 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 0.324 | N | 0.533 | 0.22 | 0.344017737713 | gnomAD-4.0.0 | 1.59352E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86159E-06 | 0 | 0 |
| R/K | rs751381334  |
-0.766 | None | N | 0.081 | 0.145 | 0.0762999501168 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs751381334 |
-0.766 | None | N | 0.081 | 0.145 | 0.0762999501168 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93498E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs751381334 |
-0.766 | None | N | 0.081 | 0.145 | 0.0762999501168 | gnomAD-4.0.0 | 6.57454E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.93498E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | None | None | 0.324 | N | 0.489 | 0.189 | 0.342400092842 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31252E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6352 | likely_pathogenic | 0.5672 | pathogenic | -1.347 | Destabilizing | 0.116 | N | 0.392 | neutral | None | None | None | None | N |
| R/C | 0.2326 | likely_benign | 0.2018 | benign | -1.206 | Destabilizing | 0.981 | D | 0.617 | neutral | None | None | None | None | N |
| R/D | 0.8861 | likely_pathogenic | 0.8516 | pathogenic | -0.011 | Destabilizing | 0.388 | N | 0.543 | neutral | None | None | None | None | N |
| R/E | 0.6084 | likely_pathogenic | 0.5487 | ambiguous | 0.125 | Stabilizing | 0.116 | N | 0.376 | neutral | None | None | None | None | N |
| R/F | 0.6436 | likely_pathogenic | 0.589 | pathogenic | -1.217 | Destabilizing | 0.932 | D | 0.624 | neutral | None | None | None | None | N |
| R/G | 0.6155 | likely_pathogenic | 0.5468 | ambiguous | -1.648 | Destabilizing | 0.324 | N | 0.533 | neutral | N | 0.463760418 | None | None | N |
| R/H | 0.1353 | likely_benign | 0.1218 | benign | -1.879 | Destabilizing | 0.818 | D | 0.549 | neutral | None | None | None | None | N |
| R/I | 0.3498 | ambiguous | 0.324 | benign | -0.524 | Destabilizing | 0.773 | D | 0.629 | neutral | N | 0.46274646 | None | None | N |
| R/K | 0.0879 | likely_benign | 0.0752 | benign | -0.97 | Destabilizing | None | N | 0.081 | neutral | N | 0.331335036 | None | None | N |
| R/L | 0.2895 | likely_benign | 0.2474 | benign | -0.524 | Destabilizing | 0.388 | N | 0.533 | neutral | None | None | None | None | N |
| R/M | 0.3555 | ambiguous | 0.3165 | benign | -0.773 | Destabilizing | 0.932 | D | 0.574 | neutral | None | None | None | None | N |
| R/N | 0.7884 | likely_pathogenic | 0.734 | pathogenic | -0.443 | Destabilizing | 0.388 | N | 0.458 | neutral | None | None | None | None | N |
| R/P | 0.9366 | likely_pathogenic | 0.9202 | pathogenic | -0.781 | Destabilizing | 0.563 | D | 0.591 | neutral | None | None | None | None | N |
| R/Q | 0.14 | likely_benign | 0.1276 | benign | -0.65 | Destabilizing | 0.241 | N | 0.471 | neutral | None | None | None | None | N |
| R/S | 0.7359 | likely_pathogenic | 0.6727 | pathogenic | -1.437 | Destabilizing | 0.09 | N | 0.453 | neutral | N | 0.509987031 | None | None | N |
| R/T | 0.4754 | ambiguous | 0.4167 | ambiguous | -1.108 | Destabilizing | 0.324 | N | 0.489 | neutral | N | 0.463506928 | None | None | N |
| R/V | 0.4589 | ambiguous | 0.4067 | ambiguous | -0.781 | Destabilizing | 0.388 | N | 0.599 | neutral | None | None | None | None | N |
| R/W | 0.2607 | likely_benign | 0.2204 | benign | -0.773 | Destabilizing | 0.981 | D | 0.639 | neutral | None | None | None | None | N |
| R/Y | 0.5007 | ambiguous | 0.4454 | ambiguous | -0.522 | Destabilizing | 0.932 | D | 0.605 | 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.