Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15770 | 47533;47534;47535 | chr2:178618043;178618042;178618041 | chr2:179482770;179482769;179482768 |
| N2AB | 14129 | 42610;42611;42612 | chr2:178618043;178618042;178618041 | chr2:179482770;179482769;179482768 |
| N2A | 13202 | 39829;39830;39831 | chr2:178618043;178618042;178618041 | chr2:179482770;179482769;179482768 |
| N2B | 6705 | 20338;20339;20340 | chr2:178618043;178618042;178618041 | chr2:179482770;179482769;179482768 |
| Novex-1 | 6830 | 20713;20714;20715 | chr2:178618043;178618042;178618041 | chr2:179482770;179482769;179482768 |
| Novex-2 | 6897 | 20914;20915;20916 | chr2:178618043;178618042;178618041 | chr2:179482770;179482769;179482768 |
| 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/G | None | None | 0.908 | D | 0.823 | 0.524 | 0.824649001973 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| V/M | rs376192778  |
-0.747 | 0.83 | D | 0.705 | 0.32 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs376192778 |
-0.747 | 0.83 | D | 0.705 | 0.32 | None | gnomAD-4.0.0 | 6.5825E-06 | None | None | None | None | N | None | 2.41476E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.3281 | likely_benign | 0.3699 | ambiguous | -1.263 | Destabilizing | 0.581 | D | 0.467 | neutral | N | 0.503558459 | None | None | N |
| V/C | 0.7042 | likely_pathogenic | 0.743 | pathogenic | -1.206 | Destabilizing | 0.993 | D | 0.762 | deleterious | None | None | None | None | N |
| V/D | 0.7632 | likely_pathogenic | 0.7846 | pathogenic | -0.895 | Destabilizing | 0.929 | D | 0.841 | deleterious | None | None | None | None | N |
| V/E | 0.5821 | likely_pathogenic | 0.5882 | pathogenic | -0.935 | Destabilizing | 0.908 | D | 0.806 | deleterious | D | 0.688178139 | None | None | N |
| V/F | 0.3875 | ambiguous | 0.3913 | ambiguous | -1.276 | Destabilizing | 0.866 | D | 0.809 | deleterious | None | None | None | None | N |
| V/G | 0.4673 | ambiguous | 0.4893 | ambiguous | -1.513 | Destabilizing | 0.908 | D | 0.823 | deleterious | D | 0.65194985 | None | None | N |
| V/H | 0.8056 | likely_pathogenic | 0.8162 | pathogenic | -1.085 | Destabilizing | 0.993 | D | 0.832 | deleterious | None | None | None | None | N |
| V/I | 0.0782 | likely_benign | 0.0874 | benign | -0.699 | Destabilizing | 0.006 | N | 0.265 | neutral | None | None | None | None | N |
| V/K | 0.5549 | ambiguous | 0.5577 | ambiguous | -0.877 | Destabilizing | 0.929 | D | 0.808 | deleterious | None | None | None | None | N |
| V/L | 0.3695 | ambiguous | 0.4245 | ambiguous | -0.699 | Destabilizing | 0.09 | N | 0.387 | neutral | D | 0.523417025 | None | None | N |
| V/M | 0.2378 | likely_benign | 0.2503 | benign | -0.631 | Destabilizing | 0.83 | D | 0.705 | prob.neutral | D | 0.628938466 | None | None | N |
| V/N | 0.5522 | ambiguous | 0.5892 | pathogenic | -0.683 | Destabilizing | 0.976 | D | 0.839 | deleterious | None | None | None | None | N |
| V/P | 0.8906 | likely_pathogenic | 0.9075 | pathogenic | -0.853 | Destabilizing | 0.976 | D | 0.826 | deleterious | None | None | None | None | N |
| V/Q | 0.5547 | ambiguous | 0.5556 | ambiguous | -0.915 | Destabilizing | 0.976 | D | 0.822 | deleterious | None | None | None | None | N |
| V/R | 0.5094 | ambiguous | 0.5097 | ambiguous | -0.415 | Destabilizing | 0.929 | D | 0.839 | deleterious | None | None | None | None | N |
| V/S | 0.4339 | ambiguous | 0.4637 | ambiguous | -1.231 | Destabilizing | 0.929 | D | 0.805 | deleterious | None | None | None | None | N |
| V/T | 0.2406 | likely_benign | 0.2504 | benign | -1.157 | Destabilizing | 0.648 | D | 0.597 | neutral | None | None | None | None | N |
| V/W | 0.9208 | likely_pathogenic | 0.9172 | pathogenic | -1.357 | Destabilizing | 0.993 | D | 0.825 | deleterious | None | None | None | None | N |
| V/Y | 0.7511 | likely_pathogenic | 0.7475 | pathogenic | -1.035 | Destabilizing | 0.929 | D | 0.815 | deleterious | 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.