Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17518 | 52777;52778;52779 | chr2:178608331;178608330;178608329 | chr2:179473058;179473057;179473056 |
| N2AB | 15877 | 47854;47855;47856 | chr2:178608331;178608330;178608329 | chr2:179473058;179473057;179473056 |
| N2A | 14950 | 45073;45074;45075 | chr2:178608331;178608330;178608329 | chr2:179473058;179473057;179473056 |
| N2B | 8453 | 25582;25583;25584 | chr2:178608331;178608330;178608329 | chr2:179473058;179473057;179473056 |
| Novex-1 | 8578 | 25957;25958;25959 | chr2:178608331;178608330;178608329 | chr2:179473058;179473057;179473056 |
| Novex-2 | 8645 | 26158;26159;26160 | chr2:178608331;178608330;178608329 | chr2:179473058;179473057;179473056 |
| 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/C | rs200974180  |
-1.03 | 1.0 | N | 0.777 | 0.449 | 0.634164238192 | gnomAD-2.1.1 | 7.18E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| R/C | rs200974180 |
-1.03 | 1.0 | N | 0.777 | 0.449 | 0.634164238192 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs200974180 |
-1.03 | 1.0 | N | 0.777 | 0.449 | 0.634164238192 | gnomAD-4.0.0 | 5.58226E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.6326E-06 | 0 | 0 |
| R/H | rs559590585 |
-1.915 | 1.0 | N | 0.733 | 0.446 | 0.300110245524 | gnomAD-2.1.1 | 4.05E-05 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 5.66E-05 | None | 0 | None | 0 | 7.16E-05 | 0 |
| R/H | rs559590585 |
-1.915 | 1.0 | N | 0.733 | 0.446 | 0.300110245524 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 4.42E-05 | 0 | 0 |
| R/H | rs559590585 |
-1.915 | 1.0 | N | 0.733 | 0.446 | 0.300110245524 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/H | rs559590585 |
-1.915 | 1.0 | N | 0.733 | 0.446 | 0.300110245524 | gnomAD-4.0.0 | 1.6746E-05 | None | None | None | None | N | None | 1.33408E-05 | 6.67757E-05 | None | 0 | 2.24477E-05 | None | 0 | 0 | 1.61137E-05 | 0 | 3.20533E-05 |
| R/P | rs559590585 |
None | 1.0 | N | 0.788 | 0.465 | 0.404034981753 | gnomAD-4.0.0 | 6.84789E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99915E-07 | 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 | 0.9523 | likely_pathogenic | 0.8837 | pathogenic | -1.132 | Destabilizing | 0.999 | D | 0.599 | neutral | None | None | None | None | N |
| R/C | 0.7374 | likely_pathogenic | 0.5778 | pathogenic | -0.99 | Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.497159269 | None | None | N |
| R/D | 0.9917 | likely_pathogenic | 0.9823 | pathogenic | -0.124 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| R/E | 0.9515 | likely_pathogenic | 0.8906 | pathogenic | 0.05 | Stabilizing | 0.999 | D | 0.607 | neutral | None | None | None | None | N |
| R/F | 0.9725 | likely_pathogenic | 0.9371 | pathogenic | -0.692 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| R/G | 0.9483 | likely_pathogenic | 0.8875 | pathogenic | -1.49 | Destabilizing | 1.0 | D | 0.745 | deleterious | N | 0.482409148 | None | None | N |
| R/H | 0.5485 | ambiguous | 0.3979 | ambiguous | -1.731 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.47098671 | None | None | N |
| R/I | 0.8831 | likely_pathogenic | 0.7496 | pathogenic | -0.142 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| R/K | 0.3268 | likely_benign | 0.21 | benign | -0.902 | Destabilizing | 0.998 | D | 0.452 | neutral | None | None | None | None | N |
| R/L | 0.8198 | likely_pathogenic | 0.6715 | pathogenic | -0.142 | Destabilizing | 1.0 | D | 0.745 | deleterious | N | 0.516518719 | None | None | N |
| R/M | 0.9061 | likely_pathogenic | 0.7703 | pathogenic | -0.558 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| R/N | 0.9839 | likely_pathogenic | 0.9651 | pathogenic | -0.539 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| R/P | 0.8814 | likely_pathogenic | 0.7796 | pathogenic | -0.453 | Destabilizing | 1.0 | D | 0.788 | deleterious | N | 0.496874166 | None | None | N |
| R/Q | 0.5382 | ambiguous | 0.3574 | ambiguous | -0.582 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/S | 0.9808 | likely_pathogenic | 0.9559 | pathogenic | -1.387 | Destabilizing | 1.0 | D | 0.776 | deleterious | N | 0.519190878 | None | None | N |
| R/T | 0.9344 | likely_pathogenic | 0.8306 | pathogenic | -1.001 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| R/V | 0.8908 | likely_pathogenic | 0.768 | pathogenic | -0.453 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| R/W | 0.7819 | likely_pathogenic | 0.626 | pathogenic | -0.266 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| R/Y | 0.94 | likely_pathogenic | 0.878 | pathogenic | -0.044 | Destabilizing | 1.0 | D | 0.801 | deleterious | 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.