Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3152 | 9679;9680;9681 | chr2:178767776;178767775;178767774 | chr2:179632503;179632502;179632501 |
| N2AB | 3152 | 9679;9680;9681 | chr2:178767776;178767775;178767774 | chr2:179632503;179632502;179632501 |
| N2A | 3152 | 9679;9680;9681 | chr2:178767776;178767775;178767774 | chr2:179632503;179632502;179632501 |
| N2B | 3106 | 9541;9542;9543 | chr2:178767776;178767775;178767774 | chr2:179632503;179632502;179632501 |
| Novex-1 | 3106 | 9541;9542;9543 | chr2:178767776;178767775;178767774 | chr2:179632503;179632502;179632501 |
| Novex-2 | 3106 | 9541;9542;9543 | chr2:178767776;178767775;178767774 | chr2:179632503;179632502;179632501 |
| Novex-3 | 3152 | 9679;9680;9681 | chr2:178767776;178767775;178767774 | chr2:179632503;179632502;179632501 |
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/M | None | None | 0.188 | N | 0.512 | 0.153 | 0.456089687795 | gnomAD-4.0.0 | 1.59061E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85657E-06 | 0 | 0 |
| I/T | rs1228152341  |
-0.67 | 0.027 | N | 0.493 | 0.252 | 0.589785090976 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| I/T | rs1228152341 |
-0.67 | 0.027 | N | 0.493 | 0.252 | 0.589785090976 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs1228152341 |
-0.67 | 0.027 | N | 0.493 | 0.252 | 0.589785090976 | gnomAD-4.0.0 | 6.57004E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46985E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.513 | ambiguous | 0.5245 | ambiguous | -0.917 | Destabilizing | None | N | 0.184 | neutral | None | None | None | None | N |
| I/C | 0.8462 | likely_pathogenic | 0.8274 | pathogenic | -0.69 | Destabilizing | 0.791 | D | 0.539 | neutral | None | None | None | None | N |
| I/D | 0.8975 | likely_pathogenic | 0.9081 | pathogenic | -0.379 | Destabilizing | 0.149 | N | 0.582 | neutral | None | None | None | None | N |
| I/E | 0.7803 | likely_pathogenic | 0.797 | pathogenic | -0.437 | Destabilizing | 0.149 | N | 0.587 | neutral | None | None | None | None | N |
| I/F | 0.2485 | likely_benign | 0.2534 | benign | -0.681 | Destabilizing | 0.188 | N | 0.491 | neutral | N | 0.504618731 | None | None | N |
| I/G | 0.8144 | likely_pathogenic | 0.8173 | pathogenic | -1.137 | Destabilizing | 0.081 | N | 0.555 | neutral | None | None | None | None | N |
| I/H | 0.7329 | likely_pathogenic | 0.7375 | pathogenic | -0.326 | Destabilizing | 0.935 | D | 0.535 | neutral | None | None | None | None | N |
| I/K | 0.608 | likely_pathogenic | 0.634 | pathogenic | -0.62 | Destabilizing | 0.149 | N | 0.59 | neutral | None | None | None | None | N |
| I/L | 0.1014 | likely_benign | 0.0889 | benign | -0.435 | Destabilizing | None | N | 0.099 | neutral | N | 0.478735164 | None | None | N |
| I/M | 0.1298 | likely_benign | 0.1239 | benign | -0.492 | Destabilizing | 0.188 | N | 0.512 | neutral | N | 0.504761662 | None | None | N |
| I/N | 0.5465 | ambiguous | 0.5664 | pathogenic | -0.414 | Destabilizing | 0.317 | N | 0.567 | neutral | N | 0.490381723 | None | None | N |
| I/P | 0.7861 | likely_pathogenic | 0.8114 | pathogenic | -0.563 | Destabilizing | 0.555 | D | 0.567 | neutral | None | None | None | None | N |
| I/Q | 0.6329 | likely_pathogenic | 0.6369 | pathogenic | -0.617 | Destabilizing | 0.555 | D | 0.579 | neutral | None | None | None | None | N |
| I/R | 0.5001 | ambiguous | 0.5249 | ambiguous | -0.037 | Destabilizing | 0.555 | D | 0.566 | neutral | None | None | None | None | N |
| I/S | 0.5419 | ambiguous | 0.5696 | pathogenic | -0.908 | Destabilizing | 0.005 | N | 0.278 | neutral | N | 0.457475873 | None | None | N |
| I/T | 0.4722 | ambiguous | 0.5037 | ambiguous | -0.856 | Destabilizing | 0.027 | N | 0.493 | neutral | N | 0.502341142 | None | None | N |
| I/V | 0.0907 | likely_benign | 0.0926 | benign | -0.563 | Destabilizing | 0.012 | N | 0.2 | neutral | N | 0.502194723 | None | None | N |
| I/W | 0.822 | likely_pathogenic | 0.8158 | pathogenic | -0.702 | Destabilizing | 0.935 | D | 0.559 | neutral | None | None | None | None | N |
| I/Y | 0.6703 | likely_pathogenic | 0.6697 | pathogenic | -0.48 | Destabilizing | 0.555 | D | 0.568 | 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.