Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21371 | 64336;64337;64338 | chr2:178586790;178586789;178586788 | chr2:179451517;179451516;179451515 |
| N2AB | 19730 | 59413;59414;59415 | chr2:178586790;178586789;178586788 | chr2:179451517;179451516;179451515 |
| N2A | 18803 | 56632;56633;56634 | chr2:178586790;178586789;178586788 | chr2:179451517;179451516;179451515 |
| N2B | 12306 | 37141;37142;37143 | chr2:178586790;178586789;178586788 | chr2:179451517;179451516;179451515 |
| Novex-1 | 12431 | 37516;37517;37518 | chr2:178586790;178586789;178586788 | chr2:179451517;179451516;179451515 |
| Novex-2 | 12498 | 37717;37718;37719 | chr2:178586790;178586789;178586788 | chr2:179451517;179451516;179451515 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs748901968  |
None | 0.549 | N | 0.577 | 0.221 | 0.498323335527 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/G | rs748901968 |
None | 0.549 | N | 0.577 | 0.221 | 0.498323335527 | gnomAD-4.0.0 | 1.30258E-05 | None | None | None | None | N | None | 0 | 1.67246E-05 | None | 0 | 0 | None | 0 | 0 | 1.52657E-05 | 0 | 3.20554E-05 |
| R/S | rs2049074403 |
None | 0.379 | N | 0.557 | 0.18 | 0.286465849087 | gnomAD-4.0.0 | 1.59492E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43997E-05 | 0 |
| R/T | None | None | 0.549 | N | 0.586 | 0.217 | 0.409398589964 | gnomAD-4.0.0 | 1.59501E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86339E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7285 | likely_pathogenic | 0.5765 | pathogenic | -0.936 | Destabilizing | 0.25 | N | 0.52 | neutral | None | None | None | None | N |
| R/C | 0.4626 | ambiguous | 0.328 | benign | -0.873 | Destabilizing | 0.992 | D | 0.623 | neutral | None | None | None | None | N |
| R/D | 0.9441 | likely_pathogenic | 0.89 | pathogenic | -0.099 | Destabilizing | 0.617 | D | 0.597 | neutral | None | None | None | None | N |
| R/E | 0.6676 | likely_pathogenic | 0.5271 | ambiguous | 0.096 | Stabilizing | 0.25 | N | 0.511 | neutral | None | None | None | None | N |
| R/F | 0.8909 | likely_pathogenic | 0.8065 | pathogenic | -0.265 | Destabilizing | 0.972 | D | 0.61 | neutral | None | None | None | None | N |
| R/G | 0.5913 | likely_pathogenic | 0.4354 | ambiguous | -1.32 | Destabilizing | 0.549 | D | 0.577 | neutral | N | 0.421992405 | None | None | N |
| R/H | 0.4067 | ambiguous | 0.2884 | benign | -1.409 | Destabilizing | 0.92 | D | 0.529 | neutral | None | None | None | None | N |
| R/I | 0.631 | likely_pathogenic | 0.4516 | ambiguous | 0.133 | Stabilizing | 0.92 | D | 0.611 | neutral | None | None | None | None | N |
| R/K | 0.1883 | likely_benign | 0.1352 | benign | -0.778 | Destabilizing | 0.001 | N | 0.137 | neutral | N | 0.429342452 | None | None | N |
| R/L | 0.5274 | ambiguous | 0.388 | ambiguous | 0.133 | Stabilizing | 0.617 | D | 0.577 | neutral | None | None | None | None | N |
| R/M | 0.6412 | likely_pathogenic | 0.4511 | ambiguous | -0.418 | Destabilizing | 0.963 | D | 0.577 | neutral | N | 0.494028648 | None | None | N |
| R/N | 0.9065 | likely_pathogenic | 0.8184 | pathogenic | -0.546 | Destabilizing | 0.617 | D | 0.537 | neutral | None | None | None | None | N |
| R/P | 0.9258 | likely_pathogenic | 0.8851 | pathogenic | -0.204 | Destabilizing | 0.92 | D | 0.597 | neutral | None | None | None | None | N |
| R/Q | 0.2175 | likely_benign | 0.1518 | benign | -0.477 | Destabilizing | 0.447 | N | 0.569 | neutral | None | None | None | None | N |
| R/S | 0.8482 | likely_pathogenic | 0.7317 | pathogenic | -1.316 | Destabilizing | 0.379 | N | 0.557 | neutral | N | 0.435305632 | None | None | N |
| R/T | 0.6945 | likely_pathogenic | 0.5027 | ambiguous | -0.905 | Destabilizing | 0.549 | D | 0.586 | neutral | N | 0.44051945 | None | None | N |
| R/V | 0.6476 | likely_pathogenic | 0.4897 | ambiguous | -0.204 | Destabilizing | 0.85 | D | 0.584 | neutral | None | None | None | None | N |
| R/W | 0.538 | ambiguous | 0.3969 | ambiguous | 0.146 | Stabilizing | 0.99 | D | 0.667 | neutral | N | 0.482880129 | None | None | N |
| R/Y | 0.7801 | likely_pathogenic | 0.6583 | pathogenic | 0.358 | Stabilizing | 0.972 | D | 0.618 | 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.