Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3376 | 10351;10352;10353 | chr2:178759161;178759160;178759159 | chr2:179623888;179623887;179623886 |
| N2AB | 3376 | 10351;10352;10353 | chr2:178759161;178759160;178759159 | chr2:179623888;179623887;179623886 |
| N2A | 3376 | 10351;10352;10353 | chr2:178759161;178759160;178759159 | chr2:179623888;179623887;179623886 |
| N2B | 3330 | 10213;10214;10215 | chr2:178759161;178759160;178759159 | chr2:179623888;179623887;179623886 |
| Novex-1 | 3330 | 10213;10214;10215 | chr2:178759161;178759160;178759159 | chr2:179623888;179623887;179623886 |
| Novex-2 | 3330 | 10213;10214;10215 | chr2:178759161;178759160;178759159 | chr2:179623888;179623887;179623886 |
| Novex-3 | 3376 | 10351;10352;10353 | chr2:178759161;178759160;178759159 | chr2:179623888;179623887;179623886 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs781368765  |
0.966 | 0.574 | N | 0.611 | 0.28 | 0.615590475704 | gnomAD-2.1.1 | 2.49E-05 | None | None | None | None | N | None | 2.00481E-04 | 2.83E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/L | rs781368765 |
0.966 | 0.574 | N | 0.611 | 0.28 | 0.615590475704 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.20825E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/L | rs781368765 |
0.966 | 0.574 | N | 0.611 | 0.28 | 0.615590475704 | gnomAD-4.0.0 | 9.29588E-06 | None | None | None | None | N | None | 1.60304E-04 | 1.66767E-05 | None | 0 | 0 | None | 0 | 0 | 8.47525E-07 | 1.09837E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1044 | likely_benign | 0.0849 | benign | -0.363 | Destabilizing | 0.001 | N | 0.25 | neutral | N | 0.516794867 | None | None | N |
| S/C | 0.1716 | likely_benign | 0.1359 | benign | -0.014 | Destabilizing | 0.005 | N | 0.517 | neutral | None | None | None | None | N |
| S/D | 0.499 | ambiguous | 0.4861 | ambiguous | -0.743 | Destabilizing | 0.388 | N | 0.615 | neutral | None | None | None | None | N |
| S/E | 0.5327 | ambiguous | 0.5464 | ambiguous | -0.569 | Destabilizing | 0.388 | N | 0.621 | neutral | None | None | None | None | N |
| S/F | 0.2146 | likely_benign | 0.1785 | benign | -0.361 | Destabilizing | 0.818 | D | 0.621 | neutral | None | None | None | None | N |
| S/G | 0.187 | likely_benign | 0.154 | benign | -0.735 | Destabilizing | 0.116 | N | 0.584 | neutral | None | None | None | None | N |
| S/H | 0.3868 | ambiguous | 0.3735 | ambiguous | -1.047 | Destabilizing | 0.981 | D | 0.599 | neutral | None | None | None | None | N |
| S/I | 0.2162 | likely_benign | 0.1803 | benign | 0.57 | Stabilizing | 0.527 | D | 0.632 | neutral | None | None | None | None | N |
| S/K | 0.7781 | likely_pathogenic | 0.752 | pathogenic | 0.145 | Stabilizing | 0.388 | N | 0.619 | neutral | None | None | None | None | N |
| S/L | 0.1378 | likely_benign | 0.1115 | benign | 0.57 | Stabilizing | 0.574 | D | 0.611 | neutral | N | 0.513533318 | None | None | N |
| S/M | 0.2661 | likely_benign | 0.2064 | benign | 0.403 | Stabilizing | 0.944 | D | 0.609 | neutral | None | None | None | None | N |
| S/N | 0.1884 | likely_benign | 0.1757 | benign | -0.464 | Destabilizing | 0.388 | N | 0.625 | neutral | None | None | None | None | N |
| S/P | 0.9429 | likely_pathogenic | 0.9139 | pathogenic | 0.293 | Stabilizing | 0.773 | D | 0.629 | neutral | D | 0.668399199 | None | None | N |
| S/Q | 0.5347 | ambiguous | 0.5317 | ambiguous | -0.233 | Destabilizing | 0.818 | D | 0.617 | neutral | None | None | None | None | N |
| S/R | 0.655 | likely_pathogenic | 0.6312 | pathogenic | -0.207 | Destabilizing | 0.69 | D | 0.627 | neutral | None | None | None | None | N |
| S/T | 0.0955 | likely_benign | 0.0835 | benign | -0.196 | Destabilizing | 0.001 | N | 0.265 | neutral | N | 0.430832586 | None | None | N |
| S/V | 0.2339 | likely_benign | 0.1907 | benign | 0.293 | Stabilizing | 0.241 | N | 0.611 | neutral | None | None | None | None | N |
| S/W | 0.4046 | ambiguous | 0.3303 | benign | -0.679 | Destabilizing | 0.99 | D | 0.695 | prob.neutral | D | 0.669497761 | None | None | N |
| S/Y | 0.2259 | likely_benign | 0.184 | benign | -0.155 | Destabilizing | 0.818 | D | 0.611 | 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.