Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15315 | 46168;46169;46170 | chr2:178620578;178620577;178620576 | chr2:179485305;179485304;179485303 |
| N2AB | 13674 | 41245;41246;41247 | chr2:178620578;178620577;178620576 | chr2:179485305;179485304;179485303 |
| N2A | 12747 | 38464;38465;38466 | chr2:178620578;178620577;178620576 | chr2:179485305;179485304;179485303 |
| N2B | 6250 | 18973;18974;18975 | chr2:178620578;178620577;178620576 | chr2:179485305;179485304;179485303 |
| Novex-1 | 6375 | 19348;19349;19350 | chr2:178620578;178620577;178620576 | chr2:179485305;179485304;179485303 |
| Novex-2 | 6442 | 19549;19550;19551 | chr2:178620578;178620577;178620576 | chr2:179485305;179485304;179485303 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/G | None | None | 1.0 | D | 0.608 | 0.562 | 0.401185642668 | gnomAD-4.0.0 | 6.00161E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.56251E-06 | 0 | 0 |
| E/K | rs1191106743  |
-0.447 | 0.999 | N | 0.616 | 0.384 | 0.270889551736 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| E/K | rs1191106743 |
-0.447 | 0.999 | N | 0.616 | 0.384 | 0.270889551736 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/K | rs1191106743 |
-0.447 | 0.999 | N | 0.616 | 0.384 | 0.270889551736 | gnomAD-4.0.0 | 3.10331E-06 | None | None | None | None | N | None | 1.33715E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.5456E-06 | 1.1005E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.4743 | ambiguous | 0.577 | pathogenic | -0.662 | Destabilizing | 0.999 | D | 0.612 | neutral | N | 0.477031165 | None | None | N |
| E/C | 0.9856 | likely_pathogenic | 0.991 | pathogenic | -0.423 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| E/D | 0.7485 | likely_pathogenic | 0.8055 | pathogenic | -0.766 | Destabilizing | 0.999 | D | 0.455 | neutral | D | 0.528544579 | None | None | N |
| E/F | 0.9819 | likely_pathogenic | 0.9899 | pathogenic | 0.041 | Stabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | N |
| E/G | 0.5219 | ambiguous | 0.6045 | pathogenic | -0.989 | Destabilizing | 1.0 | D | 0.608 | neutral | D | 0.62149396 | None | None | N |
| E/H | 0.9506 | likely_pathogenic | 0.9698 | pathogenic | 0.127 | Stabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | N |
| E/I | 0.8785 | likely_pathogenic | 0.9263 | pathogenic | 0.218 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| E/K | 0.6754 | likely_pathogenic | 0.7708 | pathogenic | -0.158 | Destabilizing | 0.999 | D | 0.616 | neutral | N | 0.474045096 | None | None | N |
| E/L | 0.8838 | likely_pathogenic | 0.9267 | pathogenic | 0.218 | Stabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | N |
| E/M | 0.9037 | likely_pathogenic | 0.9439 | pathogenic | 0.375 | Stabilizing | 1.0 | D | 0.63 | neutral | None | None | None | None | N |
| E/N | 0.8822 | likely_pathogenic | 0.9192 | pathogenic | -0.785 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| E/P | 0.8619 | likely_pathogenic | 0.9226 | pathogenic | -0.054 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| E/Q | 0.4163 | ambiguous | 0.4905 | ambiguous | -0.656 | Destabilizing | 1.0 | D | 0.618 | neutral | D | 0.58147638 | None | None | N |
| E/R | 0.7641 | likely_pathogenic | 0.832 | pathogenic | 0.25 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| E/S | 0.7505 | likely_pathogenic | 0.8111 | pathogenic | -1.01 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| E/T | 0.8236 | likely_pathogenic | 0.8787 | pathogenic | -0.727 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| E/V | 0.7041 | likely_pathogenic | 0.8011 | pathogenic | -0.054 | Destabilizing | 1.0 | D | 0.661 | neutral | N | 0.466561099 | None | None | N |
| E/W | 0.9926 | likely_pathogenic | 0.9956 | pathogenic | 0.37 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| E/Y | 0.9654 | likely_pathogenic | 0.9815 | pathogenic | 0.328 | Stabilizing | 1.0 | D | 0.65 | 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.