Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1595 | 5008;5009;5010 | chr2:178777180;178777179;178777178 | chr2:179641907;179641906;179641905 |
| N2AB | 1595 | 5008;5009;5010 | chr2:178777180;178777179;178777178 | chr2:179641907;179641906;179641905 |
| N2A | 1595 | 5008;5009;5010 | chr2:178777180;178777179;178777178 | chr2:179641907;179641906;179641905 |
| N2B | 1549 | 4870;4871;4872 | chr2:178777180;178777179;178777178 | chr2:179641907;179641906;179641905 |
| Novex-1 | 1549 | 4870;4871;4872 | chr2:178777180;178777179;178777178 | chr2:179641907;179641906;179641905 |
| Novex-2 | 1549 | 4870;4871;4872 | chr2:178777180;178777179;178777178 | chr2:179641907;179641906;179641905 |
| Novex-3 | 1595 | 5008;5009;5010 | chr2:178777180;178777179;178777178 | chr2:179641907;179641906;179641905 |
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/S | rs1012905833  |
-0.631 | 1.0 | N | 0.715 | 0.562 | 0.808767119372 | gnomAD-2.1.1 | 1.06E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.33E-05 | 0 |
| I/S | rs1012905833 |
-0.631 | 1.0 | N | 0.715 | 0.562 | 0.808767119372 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/S | rs1012905833 |
-0.631 | 1.0 | N | 0.715 | 0.562 | 0.808767119372 | gnomAD-4.0.0 | 1.30114E-05 | None | None | None | None | N | None | 1.33494E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69492E-05 | 0 | 0 |
| I/V | None | None | 0.993 | N | 0.305 | 0.265 | 0.678929657206 | gnomAD-4.0.0 | 1.59064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85677E-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 | 0.9742 | likely_pathogenic | 0.9419 | pathogenic | -1.452 | Destabilizing | 0.999 | D | 0.57 | neutral | None | None | None | None | N |
| I/C | 0.9938 | likely_pathogenic | 0.9855 | pathogenic | -0.923 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| I/D | 0.9972 | likely_pathogenic | 0.9933 | pathogenic | -0.872 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/E | 0.9942 | likely_pathogenic | 0.9854 | pathogenic | -0.851 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| I/F | 0.8509 | likely_pathogenic | 0.7486 | pathogenic | -0.911 | Destabilizing | 1.0 | D | 0.657 | neutral | N | 0.501065761 | None | None | N |
| I/G | 0.9962 | likely_pathogenic | 0.9908 | pathogenic | -1.777 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/H | 0.9936 | likely_pathogenic | 0.9833 | pathogenic | -0.878 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| I/K | 0.9872 | likely_pathogenic | 0.9713 | pathogenic | -1.055 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| I/L | 0.5423 | ambiguous | 0.4125 | ambiguous | -0.634 | Destabilizing | 0.993 | D | 0.299 | neutral | N | 0.455606716 | None | None | N |
| I/M | 0.5543 | ambiguous | 0.4049 | ambiguous | -0.572 | Destabilizing | 1.0 | D | 0.644 | neutral | D | 0.535853725 | None | None | N |
| I/N | 0.9745 | likely_pathogenic | 0.9438 | pathogenic | -0.963 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | N | 0.507390251 | None | None | N |
| I/P | 0.9873 | likely_pathogenic | 0.9725 | pathogenic | -0.875 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/Q | 0.9915 | likely_pathogenic | 0.9785 | pathogenic | -1.083 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| I/R | 0.9756 | likely_pathogenic | 0.9523 | pathogenic | -0.479 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| I/S | 0.9762 | likely_pathogenic | 0.9499 | pathogenic | -1.558 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.495974145 | None | None | N |
| I/T | 0.963 | likely_pathogenic | 0.9182 | pathogenic | -1.415 | Destabilizing | 1.0 | D | 0.666 | neutral | N | 0.486900949 | None | None | N |
| I/V | 0.356 | ambiguous | 0.2589 | benign | -0.875 | Destabilizing | 0.993 | D | 0.305 | neutral | N | 0.494988138 | None | None | N |
| I/W | 0.9926 | likely_pathogenic | 0.9846 | pathogenic | -0.999 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/Y | 0.9744 | likely_pathogenic | 0.9507 | pathogenic | -0.77 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | 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.