Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31321 | 94186;94187;94188 | chr2:178547665;178547664;178547663 | chr2:179412392;179412391;179412390 |
| N2AB | 29680 | 89263;89264;89265 | chr2:178547665;178547664;178547663 | chr2:179412392;179412391;179412390 |
| N2A | 28753 | 86482;86483;86484 | chr2:178547665;178547664;178547663 | chr2:179412392;179412391;179412390 |
| N2B | 22256 | 66991;66992;66993 | chr2:178547665;178547664;178547663 | chr2:179412392;179412391;179412390 |
| Novex-1 | 22381 | 67366;67367;67368 | chr2:178547665;178547664;178547663 | chr2:179412392;179412391;179412390 |
| Novex-2 | 22448 | 67567;67568;67569 | chr2:178547665;178547664;178547663 | chr2:179412392;179412391;179412390 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | None | None | 0.638 | N | 0.653 | 0.255 | 0.727734521826 | gnomAD-4.0.0 | 6.84169E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99431E-07 | 0 | 0 |
| V/I | rs794729535  |
-0.6 | 0.001 | N | 0.165 | 0.182 | 0.283371740733 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs794729535 |
-0.6 | 0.001 | N | 0.165 | 0.182 | 0.283371740733 | gnomAD-4.0.0 | 1.36834E-06 | None | None | None | None | N | None | 0 | 2.23634E-05 | None | 0 | 0 | None | 0 | 0 | 8.99433E-07 | 0 | 0 |
| V/L | None | None | 0.034 | N | 0.292 | 0.183 | 0.307966526162 | gnomAD-4.0.0 | 6.84169E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99431E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4807 | ambiguous | 0.4802 | ambiguous | -1.236 | Destabilizing | 0.334 | N | 0.41 | neutral | N | 0.475082222 | None | None | N |
| V/C | 0.8136 | likely_pathogenic | 0.8023 | pathogenic | -1.175 | Destabilizing | 0.982 | D | 0.626 | neutral | None | None | None | None | N |
| V/D | 0.8744 | likely_pathogenic | 0.8849 | pathogenic | -1.098 | Destabilizing | 0.781 | D | 0.733 | prob.delet. | D | 0.527522109 | None | None | N |
| V/E | 0.7269 | likely_pathogenic | 0.7567 | pathogenic | -1.146 | Destabilizing | 0.826 | D | 0.675 | neutral | None | None | None | None | N |
| V/F | 0.3493 | ambiguous | 0.3674 | ambiguous | -1.354 | Destabilizing | 0.638 | D | 0.653 | neutral | N | 0.490935206 | None | None | N |
| V/G | 0.644 | likely_pathogenic | 0.6306 | pathogenic | -1.469 | Destabilizing | 0.781 | D | 0.73 | prob.delet. | N | 0.502038022 | None | None | N |
| V/H | 0.8617 | likely_pathogenic | 0.878 | pathogenic | -1.106 | Destabilizing | 0.982 | D | 0.708 | prob.delet. | None | None | None | None | N |
| V/I | 0.0626 | likely_benign | 0.0618 | benign | -0.719 | Destabilizing | 0.001 | N | 0.165 | neutral | N | 0.468322127 | None | None | N |
| V/K | 0.6118 | likely_pathogenic | 0.6828 | pathogenic | -0.878 | Destabilizing | 0.826 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/L | 0.2655 | likely_benign | 0.2721 | benign | -0.719 | Destabilizing | 0.034 | N | 0.292 | neutral | N | 0.474891185 | None | None | N |
| V/M | 0.2314 | likely_benign | 0.2289 | benign | -0.577 | Destabilizing | 0.7 | D | 0.558 | neutral | None | None | None | None | N |
| V/N | 0.7105 | likely_pathogenic | 0.7266 | pathogenic | -0.691 | Destabilizing | 0.935 | D | 0.721 | prob.delet. | None | None | None | None | N |
| V/P | 0.7743 | likely_pathogenic | 0.7578 | pathogenic | -0.858 | Destabilizing | 0.935 | D | 0.687 | prob.neutral | None | None | None | None | N |
| V/Q | 0.6543 | likely_pathogenic | 0.6821 | pathogenic | -0.95 | Destabilizing | 0.935 | D | 0.669 | neutral | None | None | None | None | N |
| V/R | 0.5852 | likely_pathogenic | 0.6461 | pathogenic | -0.419 | Destabilizing | 0.826 | D | 0.717 | prob.delet. | None | None | None | None | N |
| V/S | 0.621 | likely_pathogenic | 0.6226 | pathogenic | -1.196 | Destabilizing | 0.826 | D | 0.675 | prob.neutral | None | None | None | None | N |
| V/T | 0.4321 | ambiguous | 0.4471 | ambiguous | -1.138 | Destabilizing | 0.399 | N | 0.479 | neutral | None | None | None | None | N |
| V/W | 0.9302 | likely_pathogenic | 0.94 | pathogenic | -1.455 | Destabilizing | 0.982 | D | 0.691 | prob.neutral | None | None | None | None | N |
| V/Y | 0.7695 | likely_pathogenic | 0.786 | pathogenic | -1.118 | Destabilizing | 0.826 | D | 0.659 | 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.