Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16717 | 50374;50375;50376 | chr2:178612376;178612375;178612374 | chr2:179477103;179477102;179477101 |
| N2AB | 15076 | 45451;45452;45453 | chr2:178612376;178612375;178612374 | chr2:179477103;179477102;179477101 |
| N2A | 14149 | 42670;42671;42672 | chr2:178612376;178612375;178612374 | chr2:179477103;179477102;179477101 |
| N2B | 7652 | 23179;23180;23181 | chr2:178612376;178612375;178612374 | chr2:179477103;179477102;179477101 |
| Novex-1 | 7777 | 23554;23555;23556 | chr2:178612376;178612375;178612374 | chr2:179477103;179477102;179477101 |
| Novex-2 | 7844 | 23755;23756;23757 | chr2:178612376;178612375;178612374 | chr2:179477103;179477102;179477101 |
| 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/D | rs369623681  |
-0.52 | 0.434 | D | 0.206 | 0.157 | 0.227260227426 | gnomAD-2.1.1 | 1.08E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.57E-05 | 0 |
| E/D | rs369623681 |
-0.52 | 0.434 | D | 0.206 | 0.157 | 0.227260227426 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| E/D | rs369623681 |
-0.52 | 0.434 | D | 0.206 | 0.157 | 0.227260227426 | gnomAD-4.0.0 | 2.17067E-05 | None | None | None | None | N | None | 1.33679E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54409E-05 | 4.3929E-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 | 0.5554 | ambiguous | 0.7267 | pathogenic | -0.581 | Destabilizing | 0.998 | D | 0.657 | neutral | N | 0.502383784 | None | None | N |
| E/C | 0.9933 | likely_pathogenic | 0.9973 | pathogenic | 0.027 | Stabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| E/D | 0.2738 | likely_benign | 0.4658 | ambiguous | -0.591 | Destabilizing | 0.434 | N | 0.206 | neutral | D | 0.574879811 | None | None | N |
| E/F | 0.9899 | likely_pathogenic | 0.997 | pathogenic | -0.601 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| E/G | 0.7117 | likely_pathogenic | 0.8342 | pathogenic | -0.804 | Destabilizing | 0.999 | D | 0.639 | neutral | D | 0.598653112 | None | None | N |
| E/H | 0.96 | likely_pathogenic | 0.9875 | pathogenic | -0.678 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| E/I | 0.9077 | likely_pathogenic | 0.9642 | pathogenic | -0.018 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| E/K | 0.7641 | likely_pathogenic | 0.8948 | pathogenic | 0.151 | Stabilizing | 0.998 | D | 0.658 | neutral | N | 0.467173326 | None | None | N |
| E/L | 0.9332 | likely_pathogenic | 0.9765 | pathogenic | -0.018 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| E/M | 0.9471 | likely_pathogenic | 0.9786 | pathogenic | 0.335 | Stabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| E/N | 0.7909 | likely_pathogenic | 0.9048 | pathogenic | -0.127 | Destabilizing | 0.999 | D | 0.724 | prob.delet. | None | None | None | None | N |
| E/P | 0.8397 | likely_pathogenic | 0.9364 | pathogenic | -0.185 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| E/Q | 0.662 | likely_pathogenic | 0.8088 | pathogenic | -0.107 | Destabilizing | 0.999 | D | 0.715 | prob.delet. | N | 0.480728709 | None | None | N |
| E/R | 0.8757 | likely_pathogenic | 0.9497 | pathogenic | 0.222 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| E/S | 0.6792 | likely_pathogenic | 0.8197 | pathogenic | -0.304 | Destabilizing | 0.997 | D | 0.669 | neutral | None | None | None | None | N |
| E/T | 0.7849 | likely_pathogenic | 0.9053 | pathogenic | -0.125 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| E/V | 0.7691 | likely_pathogenic | 0.8956 | pathogenic | -0.185 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | D | 0.562738549 | None | None | N |
| E/W | 0.9973 | likely_pathogenic | 0.9992 | pathogenic | -0.472 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| E/Y | 0.9775 | likely_pathogenic | 0.9937 | pathogenic | -0.363 | Destabilizing | 1.0 | D | 0.687 | prob.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.