Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1460 | 4603;4604;4605 | chr2:178777806;178777805;178777804 | chr2:179642533;179642532;179642531 |
| N2AB | 1460 | 4603;4604;4605 | chr2:178777806;178777805;178777804 | chr2:179642533;179642532;179642531 |
| N2A | 1460 | 4603;4604;4605 | chr2:178777806;178777805;178777804 | chr2:179642533;179642532;179642531 |
| N2B | 1414 | 4465;4466;4467 | chr2:178777806;178777805;178777804 | chr2:179642533;179642532;179642531 |
| Novex-1 | 1414 | 4465;4466;4467 | chr2:178777806;178777805;178777804 | chr2:179642533;179642532;179642531 |
| Novex-2 | 1414 | 4465;4466;4467 | chr2:178777806;178777805;178777804 | chr2:179642533;179642532;179642531 |
| Novex-3 | 1460 | 4603;4604;4605 | chr2:178777806;178777805;178777804 | chr2:179642533;179642532;179642531 |
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/L | rs771127151  |
0.01 | 0.997 | N | 0.477 | 0.453 | 0.580379909603 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs771127151 |
0.01 | 0.997 | N | 0.477 | 0.453 | 0.580379909603 | gnomAD-4.0.0 | 1.59074E-06 | None | None | None | None | I | None | 0 | 2.28666E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs771127151 |
-0.318 | 1.0 | D | 0.638 | 0.429 | 0.675916937895 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 0 |
| V/M | rs771127151 |
-0.318 | 1.0 | D | 0.638 | 0.429 | 0.675916937895 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs771127151 |
-0.318 | 1.0 | D | 0.638 | 0.429 | 0.675916937895 | gnomAD-4.0.0 | 6.40387E-06 | None | None | None | None | I | None | 0 | 1.69469E-05 | None | 0 | 0 | None | 0 | 0 | 9.56869E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7837 | likely_pathogenic | 0.7929 | pathogenic | -1.04 | Destabilizing | 0.999 | D | 0.476 | neutral | D | 0.533546891 | None | None | I |
| V/C | 0.9639 | likely_pathogenic | 0.9648 | pathogenic | -0.774 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | I |
| V/D | 0.9841 | likely_pathogenic | 0.9822 | pathogenic | -0.873 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| V/E | 0.9359 | likely_pathogenic | 0.9351 | pathogenic | -0.891 | Destabilizing | 1.0 | D | 0.655 | neutral | D | 0.535706775 | None | None | I |
| V/F | 0.6863 | likely_pathogenic | 0.6442 | pathogenic | -0.77 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| V/G | 0.8939 | likely_pathogenic | 0.8874 | pathogenic | -1.306 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | D | 0.623948217 | None | None | I |
| V/H | 0.9733 | likely_pathogenic | 0.9689 | pathogenic | -0.71 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| V/I | 0.1236 | likely_benign | 0.1167 | benign | -0.433 | Destabilizing | 0.998 | D | 0.423 | neutral | None | None | None | None | I |
| V/K | 0.9477 | likely_pathogenic | 0.9427 | pathogenic | -1.016 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | I |
| V/L | 0.5118 | ambiguous | 0.4829 | ambiguous | -0.433 | Destabilizing | 0.997 | D | 0.477 | neutral | N | 0.470547369 | None | None | I |
| V/M | 0.5927 | likely_pathogenic | 0.5688 | pathogenic | -0.432 | Destabilizing | 1.0 | D | 0.638 | neutral | D | 0.588431502 | None | None | I |
| V/N | 0.9482 | likely_pathogenic | 0.9432 | pathogenic | -0.859 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| V/P | 0.979 | likely_pathogenic | 0.9774 | pathogenic | -0.6 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| V/Q | 0.8958 | likely_pathogenic | 0.8875 | pathogenic | -1.018 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| V/R | 0.9037 | likely_pathogenic | 0.8931 | pathogenic | -0.458 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| V/S | 0.8617 | likely_pathogenic | 0.8564 | pathogenic | -1.306 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| V/T | 0.7561 | likely_pathogenic | 0.7597 | pathogenic | -1.218 | Destabilizing | 0.999 | D | 0.587 | neutral | None | None | None | None | I |
| V/W | 0.9914 | likely_pathogenic | 0.9902 | pathogenic | -0.942 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| V/Y | 0.9571 | likely_pathogenic | 0.9502 | pathogenic | -0.652 | Destabilizing | 1.0 | D | 0.675 | 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.