Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26695 | 80308;80309;80310 | chr2:178566049;178566048;178566047 | chr2:179430776;179430775;179430774 |
| N2AB | 25054 | 75385;75386;75387 | chr2:178566049;178566048;178566047 | chr2:179430776;179430775;179430774 |
| N2A | 24127 | 72604;72605;72606 | chr2:178566049;178566048;178566047 | chr2:179430776;179430775;179430774 |
| N2B | 17630 | 53113;53114;53115 | chr2:178566049;178566048;178566047 | chr2:179430776;179430775;179430774 |
| Novex-1 | 17755 | 53488;53489;53490 | chr2:178566049;178566048;178566047 | chr2:179430776;179430775;179430774 |
| Novex-2 | 17822 | 53689;53690;53691 | chr2:178566049;178566048;178566047 | chr2:179430776;179430775;179430774 |
| 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/L | rs772729384  |
-0.701 | None | N | 0.212 | 0.116 | 0.215109475489 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.23E-05 | 0 |
| V/L | rs772729384 |
-0.701 | None | N | 0.212 | 0.116 | 0.215109475489 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.82E-05 | 0 | 0 |
| V/L | rs772729384 |
-0.701 | None | N | 0.212 | 0.116 | 0.215109475489 | gnomAD-4.0.0 | 1.9833E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.71268E-05 | 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 | 0.3259 | likely_benign | 0.3409 | ambiguous | -1.334 | Destabilizing | 0.024 | N | 0.403 | neutral | N | 0.48413435 | None | None | N |
| V/C | 0.7078 | likely_pathogenic | 0.7562 | pathogenic | -0.982 | Destabilizing | 0.865 | D | 0.376 | neutral | None | None | None | None | N |
| V/D | 0.8485 | likely_pathogenic | 0.8418 | pathogenic | -1.493 | Destabilizing | 0.578 | D | 0.515 | neutral | None | None | None | None | N |
| V/E | 0.7284 | likely_pathogenic | 0.7406 | pathogenic | -1.55 | Destabilizing | 0.143 | N | 0.451 | neutral | N | 0.50907546 | None | None | N |
| V/F | 0.3439 | ambiguous | 0.3489 | ambiguous | -1.351 | Destabilizing | 0.338 | N | 0.367 | neutral | None | None | None | None | N |
| V/G | 0.4099 | ambiguous | 0.4468 | ambiguous | -1.575 | Destabilizing | 0.583 | D | 0.467 | neutral | D | 0.533473592 | None | None | N |
| V/H | 0.8702 | likely_pathogenic | 0.8829 | pathogenic | -1.191 | Destabilizing | 0.895 | D | 0.511 | neutral | None | None | None | None | N |
| V/I | 0.0659 | likely_benign | 0.0661 | benign | -0.792 | Destabilizing | None | N | 0.099 | neutral | None | None | None | None | N |
| V/K | 0.7492 | likely_pathogenic | 0.772 | pathogenic | -1.012 | Destabilizing | 0.326 | N | 0.455 | neutral | None | None | None | None | N |
| V/L | 0.238 | likely_benign | 0.2829 | benign | -0.792 | Destabilizing | None | N | 0.212 | neutral | N | 0.471599502 | None | None | N |
| V/M | 0.211 | likely_benign | 0.2092 | benign | -0.571 | Destabilizing | 0.216 | N | 0.431 | neutral | N | 0.491985163 | None | None | N |
| V/N | 0.6089 | likely_pathogenic | 0.622 | pathogenic | -0.79 | Destabilizing | 0.18 | N | 0.523 | neutral | None | None | None | None | N |
| V/P | 0.7273 | likely_pathogenic | 0.7714 | pathogenic | -0.939 | Destabilizing | 0.18 | N | 0.466 | neutral | None | None | None | None | N |
| V/Q | 0.6601 | likely_pathogenic | 0.6929 | pathogenic | -1.079 | Destabilizing | 0.511 | D | 0.47 | neutral | None | None | None | None | N |
| V/R | 0.6931 | likely_pathogenic | 0.7309 | pathogenic | -0.473 | Destabilizing | 0.508 | D | 0.519 | neutral | None | None | None | None | N |
| V/S | 0.4498 | ambiguous | 0.4753 | ambiguous | -1.204 | Destabilizing | 0.358 | N | 0.421 | neutral | None | None | None | None | N |
| V/T | 0.2995 | likely_benign | 0.3149 | benign | -1.166 | Destabilizing | 0.031 | N | 0.371 | neutral | None | None | None | None | N |
| V/W | 0.897 | likely_pathogenic | 0.9095 | pathogenic | -1.474 | Destabilizing | 0.969 | D | 0.638 | neutral | None | None | None | None | N |
| V/Y | 0.7149 | likely_pathogenic | 0.748 | pathogenic | -1.167 | Destabilizing | 0.508 | D | 0.407 | 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.