Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18091 | 54496;54497;54498 | chr2:178604818;178604817;178604816 | chr2:179469545;179469544;179469543 |
| N2AB | 16450 | 49573;49574;49575 | chr2:178604818;178604817;178604816 | chr2:179469545;179469544;179469543 |
| N2A | 15523 | 46792;46793;46794 | chr2:178604818;178604817;178604816 | chr2:179469545;179469544;179469543 |
| N2B | 9026 | 27301;27302;27303 | chr2:178604818;178604817;178604816 | chr2:179469545;179469544;179469543 |
| Novex-1 | 9151 | 27676;27677;27678 | chr2:178604818;178604817;178604816 | chr2:179469545;179469544;179469543 |
| Novex-2 | 9218 | 27877;27878;27879 | chr2:178604818;178604817;178604816 | chr2:179469545;179469544;179469543 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs2054393920  |
None | 1.0 | N | 0.369 | 0.161 | 0.235038932564 | gnomAD-4.0.0 | 1.11577E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.94921E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs751597873 |
-0.302 | 1.0 | N | 0.585 | 0.399 | 0.285698343383 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| D/N | None | None | 1.0 | N | 0.605 | 0.398 | 0.267299060538 | gnomAD-4.0.0 | 1.59423E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86362E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.8759 | likely_pathogenic | 0.8581 | pathogenic | -0.436 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | N | 0.470999936 | None | None | I |
| D/C | 0.9696 | likely_pathogenic | 0.9611 | pathogenic | 0.097 | Stabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | I |
| D/E | 0.6831 | likely_pathogenic | 0.6479 | pathogenic | -0.426 | Destabilizing | 1.0 | D | 0.369 | neutral | N | 0.520268313 | None | None | I |
| D/F | 0.966 | likely_pathogenic | 0.9581 | pathogenic | -0.498 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | I |
| D/G | 0.8509 | likely_pathogenic | 0.8219 | pathogenic | -0.635 | Destabilizing | 1.0 | D | 0.633 | neutral | N | 0.491750764 | None | None | I |
| D/H | 0.8996 | likely_pathogenic | 0.871 | pathogenic | -0.534 | Destabilizing | 1.0 | D | 0.585 | neutral | N | 0.47249442 | None | None | I |
| D/I | 0.9529 | likely_pathogenic | 0.9484 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| D/K | 0.9654 | likely_pathogenic | 0.954 | pathogenic | 0.175 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| D/L | 0.9267 | likely_pathogenic | 0.9245 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | I |
| D/M | 0.9789 | likely_pathogenic | 0.9777 | pathogenic | 0.374 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| D/N | 0.4655 | ambiguous | 0.4494 | ambiguous | -0.076 | Destabilizing | 1.0 | D | 0.605 | neutral | N | 0.512648908 | None | None | I |
| D/P | 0.9954 | likely_pathogenic | 0.9941 | pathogenic | -0.094 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | I |
| D/Q | 0.9071 | likely_pathogenic | 0.8913 | pathogenic | -0.045 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | I |
| D/R | 0.96 | likely_pathogenic | 0.9443 | pathogenic | 0.234 | Stabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| D/S | 0.7174 | likely_pathogenic | 0.6894 | pathogenic | -0.176 | Destabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | I |
| D/T | 0.8922 | likely_pathogenic | 0.8733 | pathogenic | -0.023 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| D/V | 0.8826 | likely_pathogenic | 0.869 | pathogenic | -0.094 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | N | 0.488116687 | None | None | I |
| D/W | 0.9917 | likely_pathogenic | 0.9889 | pathogenic | -0.391 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | I |
| D/Y | 0.8439 | likely_pathogenic | 0.8215 | pathogenic | -0.279 | Destabilizing | 1.0 | D | 0.621 | neutral | N | 0.502645345 | None | None | I |
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.