Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24853 | 74782;74783;74784 | chr2:178571575;178571574;178571573 | chr2:179436302;179436301;179436300 |
| N2AB | 23212 | 69859;69860;69861 | chr2:178571575;178571574;178571573 | chr2:179436302;179436301;179436300 |
| N2A | 22285 | 67078;67079;67080 | chr2:178571575;178571574;178571573 | chr2:179436302;179436301;179436300 |
| N2B | 15788 | 47587;47588;47589 | chr2:178571575;178571574;178571573 | chr2:179436302;179436301;179436300 |
| Novex-1 | 15913 | 47962;47963;47964 | chr2:178571575;178571574;178571573 | chr2:179436302;179436301;179436300 |
| Novex-2 | 15980 | 48163;48164;48165 | chr2:178571575;178571574;178571573 | chr2:179436302;179436301;179436300 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/S | rs756071728  |
-0.216 | 0.958 | N | 0.299 | 0.225 | 0.199424873507 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.98E-06 | 0 |
| T/S | rs756071728 |
-0.216 | 0.958 | N | 0.299 | 0.225 | 0.199424873507 | gnomAD-4.0.0 | 3.18492E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71899E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1619 | likely_benign | 0.1272 | benign | -0.453 | Destabilizing | 0.919 | D | 0.321 | neutral | N | 0.513209055 | None | None | N |
| T/C | 0.6532 | likely_pathogenic | 0.5374 | ambiguous | -0.097 | Destabilizing | 1.0 | D | 0.604 | neutral | None | None | None | None | N |
| T/D | 0.6561 | likely_pathogenic | 0.5293 | ambiguous | -0.069 | Destabilizing | 0.991 | D | 0.5 | neutral | None | None | None | None | N |
| T/E | 0.6474 | likely_pathogenic | 0.5505 | ambiguous | -0.165 | Destabilizing | 0.938 | D | 0.457 | neutral | None | None | None | None | N |
| T/F | 0.7016 | likely_pathogenic | 0.612 | pathogenic | -1.098 | Destabilizing | 0.998 | D | 0.641 | neutral | None | None | None | None | N |
| T/G | 0.2995 | likely_benign | 0.214 | benign | -0.538 | Destabilizing | 0.991 | D | 0.509 | neutral | None | None | None | None | N |
| T/H | 0.5459 | ambiguous | 0.4263 | ambiguous | -0.992 | Destabilizing | 0.999 | D | 0.644 | neutral | None | None | None | None | N |
| T/I | 0.7012 | likely_pathogenic | 0.6262 | pathogenic | -0.345 | Destabilizing | 0.994 | D | 0.527 | neutral | N | 0.49841349 | None | None | N |
| T/K | 0.4964 | ambiguous | 0.4177 | ambiguous | -0.264 | Destabilizing | 0.142 | N | 0.262 | neutral | N | 0.483616867 | None | None | N |
| T/L | 0.2762 | likely_benign | 0.2326 | benign | -0.345 | Destabilizing | 0.968 | D | 0.425 | neutral | None | None | None | None | N |
| T/M | 0.2072 | likely_benign | 0.1692 | benign | 0.126 | Stabilizing | 1.0 | D | 0.589 | neutral | None | None | None | None | N |
| T/N | 0.2231 | likely_benign | 0.1685 | benign | None | Stabilizing | 0.991 | D | 0.505 | neutral | None | None | None | None | N |
| T/P | 0.8052 | likely_pathogenic | 0.74 | pathogenic | -0.356 | Destabilizing | 0.994 | D | 0.528 | neutral | N | 0.48186617 | None | None | N |
| T/Q | 0.438 | ambiguous | 0.3575 | ambiguous | -0.334 | Destabilizing | 0.991 | D | 0.53 | neutral | None | None | None | None | N |
| T/R | 0.4914 | ambiguous | 0.404 | ambiguous | 0.009 | Stabilizing | 0.976 | D | 0.501 | neutral | N | 0.498298318 | None | None | N |
| T/S | 0.1167 | likely_benign | 0.0889 | benign | -0.177 | Destabilizing | 0.958 | D | 0.299 | neutral | N | 0.426896792 | None | None | N |
| T/V | 0.4716 | ambiguous | 0.4183 | ambiguous | -0.356 | Destabilizing | 0.968 | D | 0.369 | neutral | None | None | None | None | N |
| T/W | 0.918 | likely_pathogenic | 0.8594 | pathogenic | -1.084 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| T/Y | 0.6857 | likely_pathogenic | 0.567 | pathogenic | -0.795 | Destabilizing | 0.998 | D | 0.642 | 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.