Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13818 | 41677;41678;41679 | chr2:178636119;178636118;178636117 | chr2:179500846;179500845;179500844 |
| N2AB | 12177 | 36754;36755;36756 | chr2:178636119;178636118;178636117 | chr2:179500846;179500845;179500844 |
| N2A | 11250 | 33973;33974;33975 | chr2:178636119;178636118;178636117 | chr2:179500846;179500845;179500844 |
| N2B | 4753 | 14482;14483;14484 | chr2:178636119;178636118;178636117 | chr2:179500846;179500845;179500844 |
| Novex-1 | 4878 | 14857;14858;14859 | chr2:178636119;178636118;178636117 | chr2:179500846;179500845;179500844 |
| Novex-2 | 4945 | 15058;15059;15060 | chr2:178636119;178636118;178636117 | chr2:179500846;179500845;179500844 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | rs929168416  |
-0.147 | 0.772 | N | 0.538 | 0.149 | 0.379881503574 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/N | rs929168416 |
-0.147 | 0.772 | N | 0.538 | 0.149 | 0.379881503574 | gnomAD-4.0.0 | 6.84444E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15974E-05 | 0 |
| I/T | rs929168416 |
None | 0.491 | N | 0.448 | 0.204 | 0.264081493735 | gnomAD-4.0.0 | 2.05333E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69895E-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 | 0.529 | ambiguous | 0.5262 | ambiguous | -0.918 | Destabilizing | 0.345 | N | 0.358 | neutral | None | None | None | None | N |
| I/C | 0.9327 | likely_pathogenic | 0.928 | pathogenic | -0.775 | Destabilizing | 0.991 | D | 0.38 | neutral | None | None | None | None | N |
| I/D | 0.8725 | likely_pathogenic | 0.8564 | pathogenic | -0.431 | Destabilizing | 0.39 | N | 0.495 | neutral | None | None | None | None | N |
| I/E | 0.7273 | likely_pathogenic | 0.7189 | pathogenic | -0.49 | Destabilizing | 0.017 | N | 0.269 | neutral | None | None | None | None | N |
| I/F | 0.3782 | ambiguous | 0.3847 | ambiguous | -0.688 | Destabilizing | 0.772 | D | 0.325 | neutral | N | 0.337413956 | None | None | N |
| I/G | 0.9113 | likely_pathogenic | 0.9081 | pathogenic | -1.132 | Destabilizing | 0.561 | D | 0.492 | neutral | None | None | None | None | N |
| I/H | 0.8323 | likely_pathogenic | 0.8235 | pathogenic | -0.312 | Destabilizing | 0.965 | D | 0.369 | neutral | None | None | None | None | N |
| I/K | 0.6341 | likely_pathogenic | 0.6404 | pathogenic | -0.678 | Destabilizing | 0.002 | N | 0.229 | neutral | None | None | None | None | N |
| I/L | 0.2107 | likely_benign | 0.2169 | benign | -0.454 | Destabilizing | 0.001 | N | 0.111 | neutral | N | 0.333722963 | None | None | N |
| I/M | 0.1615 | likely_benign | 0.1637 | benign | -0.523 | Destabilizing | 0.772 | D | 0.4 | neutral | N | 0.344811313 | None | None | N |
| I/N | 0.5915 | likely_pathogenic | 0.5497 | ambiguous | -0.527 | Destabilizing | 0.772 | D | 0.538 | neutral | N | 0.351367457 | None | None | N |
| I/P | 0.6556 | likely_pathogenic | 0.6945 | pathogenic | -0.575 | Destabilizing | 0.901 | D | 0.537 | neutral | None | None | None | None | N |
| I/Q | 0.7316 | likely_pathogenic | 0.721 | pathogenic | -0.724 | Destabilizing | 0.818 | D | 0.538 | neutral | None | None | None | None | N |
| I/R | 0.5706 | likely_pathogenic | 0.569 | pathogenic | -0.081 | Destabilizing | 0.39 | N | 0.524 | neutral | None | None | None | None | N |
| I/S | 0.6492 | likely_pathogenic | 0.6212 | pathogenic | -1.007 | Destabilizing | 0.491 | N | 0.416 | neutral | N | 0.347496488 | None | None | N |
| I/T | 0.321 | likely_benign | 0.3244 | benign | -0.956 | Destabilizing | 0.491 | N | 0.448 | neutral | N | 0.34537723 | None | None | N |
| I/V | 0.1104 | likely_benign | 0.1196 | benign | -0.575 | Destabilizing | 0.005 | N | 0.129 | neutral | N | 0.331117055 | None | None | N |
| I/W | 0.912 | likely_pathogenic | 0.913 | pathogenic | -0.714 | Destabilizing | 0.991 | D | 0.392 | neutral | None | None | None | None | N |
| I/Y | 0.7913 | likely_pathogenic | 0.7678 | pathogenic | -0.495 | Destabilizing | 0.901 | D | 0.475 | 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.