Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16663 | 50212;50213;50214 | chr2:178612538;178612537;178612536 | chr2:179477265;179477264;179477263 |
| N2AB | 15022 | 45289;45290;45291 | chr2:178612538;178612537;178612536 | chr2:179477265;179477264;179477263 |
| N2A | 14095 | 42508;42509;42510 | chr2:178612538;178612537;178612536 | chr2:179477265;179477264;179477263 |
| N2B | 7598 | 23017;23018;23019 | chr2:178612538;178612537;178612536 | chr2:179477265;179477264;179477263 |
| Novex-1 | 7723 | 23392;23393;23394 | chr2:178612538;178612537;178612536 | chr2:179477265;179477264;179477263 |
| Novex-2 | 7790 | 23593;23594;23595 | chr2:178612538;178612537;178612536 | chr2:179477265;179477264;179477263 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs774556838  |
-1.296 | 0.925 | N | 0.469 | 0.322 | 0.626729916089 | gnomAD-2.1.1 | 1.23E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.76E-05 | 0 |
| I/T | rs774556838 |
-1.296 | 0.925 | N | 0.469 | 0.322 | 0.626729916089 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.95E-05 | 0 | 0 |
| I/T | rs774556838 |
-1.296 | 0.925 | N | 0.469 | 0.322 | 0.626729916089 | gnomAD-4.0.0 | 1.61339E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.2052E-05 | 0 | 0 |
| I/V | rs1410838349 |
None | 0.954 | N | 0.365 | 0.185 | 0.494031935134 | gnomAD-4.0.0 | 3.42538E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49995E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8741 | likely_pathogenic | 0.8494 | pathogenic | -1.708 | Destabilizing | 0.871 | D | 0.494 | neutral | None | None | None | None | N |
| I/C | 0.9246 | likely_pathogenic | 0.9168 | pathogenic | -1.697 | Destabilizing | 1.0 | D | 0.533 | neutral | None | None | None | None | N |
| I/D | 0.9932 | likely_pathogenic | 0.9921 | pathogenic | -1.848 | Destabilizing | 0.991 | D | 0.673 | neutral | None | None | None | None | N |
| I/E | 0.9861 | likely_pathogenic | 0.9826 | pathogenic | -1.845 | Destabilizing | 0.991 | D | 0.645 | neutral | None | None | None | None | N |
| I/F | 0.755 | likely_pathogenic | 0.7791 | pathogenic | -1.569 | Destabilizing | 0.998 | D | 0.441 | neutral | N | 0.50814975 | None | None | N |
| I/G | 0.9812 | likely_pathogenic | 0.9795 | pathogenic | -2.001 | Highly Destabilizing | 0.991 | D | 0.615 | neutral | None | None | None | None | N |
| I/H | 0.978 | likely_pathogenic | 0.9739 | pathogenic | -1.319 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| I/K | 0.9673 | likely_pathogenic | 0.963 | pathogenic | -1.184 | Destabilizing | 0.991 | D | 0.654 | neutral | None | None | None | None | N |
| I/L | 0.4766 | ambiguous | 0.4837 | ambiguous | -0.968 | Destabilizing | 0.954 | D | 0.343 | neutral | N | 0.483205323 | None | None | N |
| I/M | 0.3788 | ambiguous | 0.3966 | ambiguous | -0.93 | Destabilizing | 0.998 | D | 0.437 | neutral | N | 0.47299464 | None | None | N |
| I/N | 0.9293 | likely_pathogenic | 0.8971 | pathogenic | -1.168 | Destabilizing | 0.989 | D | 0.685 | prob.neutral | D | 0.583985998 | None | None | N |
| I/P | 0.9804 | likely_pathogenic | 0.9874 | pathogenic | -1.187 | Destabilizing | 0.996 | D | 0.713 | prob.delet. | None | None | None | None | N |
| I/Q | 0.9646 | likely_pathogenic | 0.9616 | pathogenic | -1.42 | Destabilizing | 0.996 | D | 0.715 | prob.delet. | None | None | None | None | N |
| I/R | 0.9548 | likely_pathogenic | 0.949 | pathogenic | -0.631 | Destabilizing | 0.996 | D | 0.713 | prob.delet. | None | None | None | None | N |
| I/S | 0.8759 | likely_pathogenic | 0.8422 | pathogenic | -1.75 | Destabilizing | 0.489 | N | 0.352 | neutral | N | 0.485289508 | None | None | N |
| I/T | 0.8041 | likely_pathogenic | 0.6934 | pathogenic | -1.631 | Destabilizing | 0.925 | D | 0.469 | neutral | N | 0.484602361 | None | None | N |
| I/V | 0.1702 | likely_benign | 0.1393 | benign | -1.187 | Destabilizing | 0.954 | D | 0.365 | neutral | N | 0.41696925 | None | None | N |
| I/W | 0.9845 | likely_pathogenic | 0.9897 | pathogenic | -1.633 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| I/Y | 0.9551 | likely_pathogenic | 0.96 | pathogenic | -1.328 | Destabilizing | 0.999 | D | 0.544 | 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.