Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24975 | 75148;75149;75150 | chr2:178571209;178571208;178571207 | chr2:179435936;179435935;179435934 |
| N2AB | 23334 | 70225;70226;70227 | chr2:178571209;178571208;178571207 | chr2:179435936;179435935;179435934 |
| N2A | 22407 | 67444;67445;67446 | chr2:178571209;178571208;178571207 | chr2:179435936;179435935;179435934 |
| N2B | 15910 | 47953;47954;47955 | chr2:178571209;178571208;178571207 | chr2:179435936;179435935;179435934 |
| Novex-1 | 16035 | 48328;48329;48330 | chr2:178571209;178571208;178571207 | chr2:179435936;179435935;179435934 |
| Novex-2 | 16102 | 48529;48530;48531 | chr2:178571209;178571208;178571207 | chr2:179435936;179435935;179435934 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/G | rs548753396  |
-0.95 | 1.0 | N | 0.596 | 0.426 | 0.586756053714 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| E/G | rs548753396 |
-0.95 | 1.0 | N | 0.596 | 0.426 | 0.586756053714 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| E/G | rs548753396 |
-0.95 | 1.0 | N | 0.596 | 0.426 | 0.586756053714 | gnomAD-4.0.0 | 6.57065E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.206 | likely_benign | 0.2092 | benign | -0.652 | Destabilizing | 0.999 | D | 0.641 | neutral | N | 0.470581863 | None | None | N |
| E/C | 0.9299 | likely_pathogenic | 0.9342 | pathogenic | -0.163 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| E/D | 0.2168 | likely_benign | 0.2328 | benign | -0.769 | Destabilizing | 0.999 | D | 0.601 | neutral | N | 0.49536207 | None | None | N |
| E/F | 0.9243 | likely_pathogenic | 0.9348 | pathogenic | -0.536 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | N |
| E/G | 0.3602 | ambiguous | 0.3737 | ambiguous | -0.913 | Destabilizing | 1.0 | D | 0.596 | neutral | N | 0.499894747 | None | None | N |
| E/H | 0.8069 | likely_pathogenic | 0.8136 | pathogenic | -0.657 | Destabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | N |
| E/I | 0.5882 | likely_pathogenic | 0.5957 | pathogenic | 0.026 | Stabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | N |
| E/K | 0.4003 | ambiguous | 0.4065 | ambiguous | -0.143 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | N | 0.480523044 | None | None | N |
| E/L | 0.6701 | likely_pathogenic | 0.6951 | pathogenic | 0.026 | Stabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| E/M | 0.6698 | likely_pathogenic | 0.68 | pathogenic | 0.353 | Stabilizing | 1.0 | D | 0.595 | neutral | None | None | None | None | N |
| E/N | 0.4895 | ambiguous | 0.5169 | ambiguous | -0.43 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| E/P | 0.5442 | ambiguous | 0.5461 | ambiguous | -0.179 | Destabilizing | 1.0 | D | 0.604 | neutral | None | None | None | None | N |
| E/Q | 0.3073 | likely_benign | 0.3022 | benign | -0.391 | Destabilizing | 1.0 | D | 0.671 | neutral | N | 0.510227465 | None | None | N |
| E/R | 0.572 | likely_pathogenic | 0.5691 | pathogenic | 0.028 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| E/S | 0.3782 | ambiguous | 0.3908 | ambiguous | -0.646 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| E/T | 0.4282 | ambiguous | 0.4419 | ambiguous | -0.442 | Destabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | N |
| E/V | 0.3785 | ambiguous | 0.387 | ambiguous | -0.179 | Destabilizing | 1.0 | D | 0.6 | neutral | N | 0.497337079 | None | None | N |
| E/W | 0.9787 | likely_pathogenic | 0.9814 | pathogenic | -0.382 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| E/Y | 0.8654 | likely_pathogenic | 0.8777 | pathogenic | -0.302 | Destabilizing | 1.0 | D | 0.599 | 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.