Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28441 | 85546;85547;85548 | chr2:178560811;178560810;178560809 | chr2:179425538;179425537;179425536 |
| N2AB | 26800 | 80623;80624;80625 | chr2:178560811;178560810;178560809 | chr2:179425538;179425537;179425536 |
| N2A | 25873 | 77842;77843;77844 | chr2:178560811;178560810;178560809 | chr2:179425538;179425537;179425536 |
| N2B | 19376 | 58351;58352;58353 | chr2:178560811;178560810;178560809 | chr2:179425538;179425537;179425536 |
| Novex-1 | 19501 | 58726;58727;58728 | chr2:178560811;178560810;178560809 | chr2:179425538;179425537;179425536 |
| Novex-2 | 19568 | 58927;58928;58929 | chr2:178560811;178560810;178560809 | chr2:179425538;179425537;179425536 |
| 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/A | None | None | None | N | 0.105 | 0.124 | 0.311079019809 | gnomAD-4.0.0 | 6.8427E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9948E-07 | 0 | 0 |
| V/G | rs759245283  |
-0.883 | 0.055 | N | 0.573 | 0.159 | 0.620116128015 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/G | rs759245283 |
-0.883 | 0.055 | N | 0.573 | 0.159 | 0.620116128015 | gnomAD-4.0.0 | 6.15843E-06 | None | None | None | None | I | None | 2.98775E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79896E-06 | 5.79697E-05 | 1.65689E-05 |
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 | 0.1674 | likely_benign | 0.1617 | benign | -0.719 | Destabilizing | None | N | 0.105 | neutral | N | 0.440010523 | None | None | I |
| V/C | 0.6352 | likely_pathogenic | 0.6467 | pathogenic | -0.817 | Destabilizing | 0.628 | D | 0.589 | neutral | None | None | None | None | I |
| V/D | 0.5987 | likely_pathogenic | 0.569 | pathogenic | -0.303 | Destabilizing | 0.356 | N | 0.667 | neutral | None | None | None | None | I |
| V/E | 0.4121 | ambiguous | 0.3961 | ambiguous | -0.363 | Destabilizing | 0.106 | N | 0.662 | neutral | D | 0.525765425 | None | None | I |
| V/F | 0.1271 | likely_benign | 0.1294 | benign | -0.668 | Destabilizing | None | N | 0.231 | neutral | None | None | None | None | I |
| V/G | 0.3176 | likely_benign | 0.3049 | benign | -0.927 | Destabilizing | 0.055 | N | 0.573 | neutral | N | 0.519436886 | None | None | I |
| V/H | 0.5646 | likely_pathogenic | 0.5662 | pathogenic | -0.376 | Destabilizing | 0.628 | D | 0.585 | neutral | None | None | None | None | I |
| V/I | 0.081 | likely_benign | 0.0801 | benign | -0.293 | Destabilizing | 0.007 | N | 0.287 | neutral | None | None | None | None | I |
| V/K | 0.4379 | ambiguous | 0.4398 | ambiguous | -0.641 | Destabilizing | 0.072 | N | 0.609 | neutral | None | None | None | None | I |
| V/L | 0.1306 | likely_benign | 0.1321 | benign | -0.293 | Destabilizing | None | N | 0.097 | neutral | N | 0.472491088 | None | None | I |
| V/M | 0.0955 | likely_benign | 0.0907 | benign | -0.445 | Destabilizing | None | N | 0.131 | neutral | N | 0.495442927 | None | None | I |
| V/N | 0.4468 | ambiguous | 0.4068 | ambiguous | -0.453 | Destabilizing | 0.356 | N | 0.659 | neutral | None | None | None | None | I |
| V/P | 0.9085 | likely_pathogenic | 0.9172 | pathogenic | -0.399 | Destabilizing | 0.356 | N | 0.671 | neutral | None | None | None | None | I |
| V/Q | 0.3609 | ambiguous | 0.3578 | ambiguous | -0.616 | Destabilizing | 0.214 | N | 0.668 | neutral | None | None | None | None | I |
| V/R | 0.372 | ambiguous | 0.3781 | ambiguous | -0.157 | Destabilizing | 0.214 | N | 0.669 | neutral | None | None | None | None | I |
| V/S | 0.2763 | likely_benign | 0.2529 | benign | -0.909 | Destabilizing | 0.038 | N | 0.553 | neutral | None | None | None | None | I |
| V/T | 0.1921 | likely_benign | 0.1775 | benign | -0.851 | Destabilizing | 0.031 | N | 0.355 | neutral | None | None | None | None | I |
| V/W | 0.6702 | likely_pathogenic | 0.6741 | pathogenic | -0.766 | Destabilizing | 0.864 | D | 0.588 | neutral | None | None | None | None | I |
| V/Y | 0.4679 | ambiguous | 0.4855 | ambiguous | -0.475 | Destabilizing | 0.038 | N | 0.624 | neutral | None | None | None | None | I |
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.