Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27304 | 82135;82136;82137 | chr2:178564222;178564221;178564220 | chr2:179428949;179428948;179428947 |
| N2AB | 25663 | 77212;77213;77214 | chr2:178564222;178564221;178564220 | chr2:179428949;179428948;179428947 |
| N2A | 24736 | 74431;74432;74433 | chr2:178564222;178564221;178564220 | chr2:179428949;179428948;179428947 |
| N2B | 18239 | 54940;54941;54942 | chr2:178564222;178564221;178564220 | chr2:179428949;179428948;179428947 |
| Novex-1 | 18364 | 55315;55316;55317 | chr2:178564222;178564221;178564220 | chr2:179428949;179428948;179428947 |
| Novex-2 | 18431 | 55516;55517;55518 | chr2:178564222;178564221;178564220 | chr2:179428949;179428948;179428947 |
| 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/T | rs753976208  |
-0.818 | 0.004 | N | 0.233 | 0.222 | None | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.27E-05 | 0 |
| I/T | rs753976208 |
-0.818 | 0.004 | N | 0.233 | 0.222 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/T | rs753976208 |
-0.818 | 0.004 | N | 0.233 | 0.222 | None | gnomAD-4.0.0 | 2.23133E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.96662E-05 | 0 | 1.60128E-05 |
| I/V | rs111362795 |
None | 0.002 | N | 0.14 | 0.058 | 0.413635276047 | gnomAD-4.0.0 | 1.77933E-05 | None | None | None | None | I | None | 3.28731E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99471E-07 | 0 | 2.31926E-04 |
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 | 0.3048 | likely_benign | 0.235 | benign | -0.93 | Destabilizing | 0.25 | N | 0.344 | neutral | None | None | None | None | I |
| I/C | 0.7423 | likely_pathogenic | 0.6422 | pathogenic | -0.609 | Destabilizing | 0.992 | D | 0.403 | neutral | None | None | None | None | I |
| I/D | 0.684 | likely_pathogenic | 0.5699 | pathogenic | -0.451 | Destabilizing | 0.85 | D | 0.503 | neutral | None | None | None | None | I |
| I/E | 0.5498 | ambiguous | 0.4572 | ambiguous | -0.518 | Destabilizing | 0.85 | D | 0.486 | neutral | None | None | None | None | I |
| I/F | 0.1756 | likely_benign | 0.1388 | benign | -0.788 | Destabilizing | 0.85 | D | 0.318 | neutral | None | None | None | None | I |
| I/G | 0.6939 | likely_pathogenic | 0.5872 | pathogenic | -1.144 | Destabilizing | 0.617 | D | 0.471 | neutral | None | None | None | None | I |
| I/H | 0.5746 | likely_pathogenic | 0.4615 | ambiguous | -0.418 | Destabilizing | 0.992 | D | 0.499 | neutral | None | None | None | None | I |
| I/K | 0.4098 | ambiguous | 0.3124 | benign | -0.61 | Destabilizing | 0.81 | D | 0.483 | neutral | N | 0.446013776 | None | None | I |
| I/L | 0.0884 | likely_benign | 0.078 | benign | -0.468 | Destabilizing | 0.001 | N | 0.117 | neutral | N | 0.396491819 | None | None | I |
| I/M | 0.1075 | likely_benign | 0.0966 | benign | -0.444 | Destabilizing | 0.81 | D | 0.383 | neutral | N | 0.477896908 | None | None | I |
| I/N | 0.3184 | likely_benign | 0.2429 | benign | -0.362 | Destabilizing | 0.85 | D | 0.511 | neutral | None | None | None | None | I |
| I/P | 0.5475 | ambiguous | 0.4651 | ambiguous | -0.589 | Destabilizing | 0.92 | D | 0.511 | neutral | None | None | None | None | I |
| I/Q | 0.4606 | ambiguous | 0.3745 | ambiguous | -0.576 | Destabilizing | 0.92 | D | 0.51 | neutral | None | None | None | None | I |
| I/R | 0.3542 | ambiguous | 0.2597 | benign | -0.029 | Destabilizing | 0.81 | D | 0.514 | neutral | N | 0.468410633 | None | None | I |
| I/S | 0.3187 | likely_benign | 0.2445 | benign | -0.83 | Destabilizing | 0.447 | N | 0.407 | neutral | None | None | None | None | I |
| I/T | 0.257 | likely_benign | 0.1915 | benign | -0.788 | Destabilizing | 0.004 | N | 0.233 | neutral | N | 0.419520608 | None | None | I |
| I/V | 0.0659 | likely_benign | 0.0622 | benign | -0.589 | Destabilizing | 0.002 | N | 0.14 | neutral | N | 0.435548853 | None | None | I |
| I/W | 0.8119 | likely_pathogenic | 0.7313 | pathogenic | -0.822 | Destabilizing | 0.992 | D | 0.535 | neutral | None | None | None | None | I |
| I/Y | 0.5427 | ambiguous | 0.4438 | ambiguous | -0.59 | Destabilizing | 0.92 | D | 0.415 | 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.