Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33701 | 101326;101327;101328 | chr2:178535514;178535513;178535512 | chr2:179400241;179400240;179400239 |
| N2AB | 32060 | 96403;96404;96405 | chr2:178535514;178535513;178535512 | chr2:179400241;179400240;179400239 |
| N2A | 31133 | 93622;93623;93624 | chr2:178535514;178535513;178535512 | chr2:179400241;179400240;179400239 |
| N2B | 24636 | 74131;74132;74133 | chr2:178535514;178535513;178535512 | chr2:179400241;179400240;179400239 |
| Novex-1 | 24761 | 74506;74507;74508 | chr2:178535514;178535513;178535512 | chr2:179400241;179400240;179400239 |
| Novex-2 | 24828 | 74707;74708;74709 | chr2:178535514;178535513;178535512 | chr2:179400241;179400240;179400239 |
| 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/I | rs754435284  |
-0.58 | None | N | 0.143 | 0.083 | 0.305410167561 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/I | rs754435284 |
-0.58 | None | N | 0.143 | 0.083 | 0.305410167561 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs754435284 |
-0.58 | None | N | 0.143 | 0.083 | 0.305410167561 | gnomAD-4.0.0 | 3.84281E-06 | None | None | None | None | N | None | 1.69102E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.67989E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4778 | ambiguous | 0.4071 | ambiguous | -0.952 | Destabilizing | 0.133 | N | 0.453 | neutral | N | 0.503880283 | None | None | N |
| V/C | 0.8435 | likely_pathogenic | 0.833 | pathogenic | -0.901 | Destabilizing | 0.976 | D | 0.591 | neutral | None | None | None | None | N |
| V/D | 0.8401 | likely_pathogenic | 0.7829 | pathogenic | -0.653 | Destabilizing | 0.866 | D | 0.714 | prob.delet. | N | 0.502340737 | None | None | N |
| V/E | 0.6971 | likely_pathogenic | 0.6544 | pathogenic | -0.729 | Destabilizing | 0.581 | D | 0.679 | prob.neutral | None | None | None | None | N |
| V/F | 0.4259 | ambiguous | 0.3455 | ambiguous | -1.221 | Destabilizing | 0.706 | D | 0.599 | neutral | N | 0.478262227 | None | None | N |
| V/G | 0.6402 | likely_pathogenic | 0.5326 | ambiguous | -1.13 | Destabilizing | 0.898 | D | 0.7 | prob.neutral | N | 0.498746339 | None | None | N |
| V/H | 0.8903 | likely_pathogenic | 0.866 | pathogenic | -0.811 | Destabilizing | 0.982 | D | 0.716 | prob.delet. | None | None | None | None | N |
| V/I | 0.0721 | likely_benign | 0.0742 | benign | -0.602 | Destabilizing | None | N | 0.143 | neutral | N | 0.431150606 | None | None | N |
| V/K | 0.7443 | likely_pathogenic | 0.6907 | pathogenic | -0.536 | Destabilizing | 0.752 | D | 0.688 | prob.neutral | None | None | None | None | N |
| V/L | 0.3964 | ambiguous | 0.3338 | benign | -0.602 | Destabilizing | 0.002 | N | 0.293 | neutral | N | 0.515038639 | None | None | N |
| V/M | 0.2891 | likely_benign | 0.2588 | benign | -0.463 | Destabilizing | 0.695 | D | 0.501 | neutral | None | None | None | None | N |
| V/N | 0.6827 | likely_pathogenic | 0.6231 | pathogenic | -0.324 | Destabilizing | 0.578 | D | 0.722 | prob.delet. | None | None | None | None | N |
| V/P | 0.8455 | likely_pathogenic | 0.7508 | pathogenic | -0.685 | Destabilizing | 0.578 | D | 0.681 | prob.neutral | None | None | None | None | N |
| V/Q | 0.7283 | likely_pathogenic | 0.6827 | pathogenic | -0.605 | Destabilizing | 0.868 | D | 0.699 | prob.neutral | None | None | None | None | N |
| V/R | 0.7232 | likely_pathogenic | 0.6438 | pathogenic | -0.117 | Destabilizing | 0.866 | D | 0.723 | prob.delet. | None | None | None | None | N |
| V/S | 0.5869 | likely_pathogenic | 0.5144 | ambiguous | -0.784 | Destabilizing | 0.777 | D | 0.587 | neutral | None | None | None | None | N |
| V/T | 0.3573 | ambiguous | 0.3393 | benign | -0.762 | Destabilizing | 0.165 | N | 0.443 | neutral | None | None | None | None | N |
| V/W | 0.9575 | likely_pathogenic | 0.9342 | pathogenic | -1.291 | Destabilizing | 0.995 | D | 0.719 | prob.delet. | None | None | None | None | N |
| V/Y | 0.8448 | likely_pathogenic | 0.7962 | pathogenic | -0.934 | Destabilizing | 0.866 | D | 0.595 | 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.