Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25522 | 76789;76790;76791 | chr2:178569568;178569567;178569566 | chr2:179434295;179434294;179434293 |
| N2AB | 23881 | 71866;71867;71868 | chr2:178569568;178569567;178569566 | chr2:179434295;179434294;179434293 |
| N2A | 22954 | 69085;69086;69087 | chr2:178569568;178569567;178569566 | chr2:179434295;179434294;179434293 |
| N2B | 16457 | 49594;49595;49596 | chr2:178569568;178569567;178569566 | chr2:179434295;179434294;179434293 |
| Novex-1 | 16582 | 49969;49970;49971 | chr2:178569568;178569567;178569566 | chr2:179434295;179434294;179434293 |
| Novex-2 | 16649 | 50170;50171;50172 | chr2:178569568;178569567;178569566 | chr2:179434295;179434294;179434293 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs372963832  |
-1.125 | 0.684 | N | 0.387 | 0.364 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| I/T | rs372963832 |
-1.125 | 0.684 | N | 0.387 | 0.364 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs372963832 |
-1.125 | 0.684 | N | 0.387 | 0.364 | None | gnomAD-4.0.0 | 1.67399E-05 | None | None | None | None | I | None | 1.3359E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.11957E-05 | 0 | 1.60226E-05 |
| I/V | rs1403999176 |
None | 0.003 | N | 0.173 | 0.06 | 0.557405679382 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.78011E-04 |
| I/V | rs1403999176 |
None | 0.003 | N | 0.173 | 0.06 | 0.557405679382 | gnomAD-4.0.0 | 5.12934E-06 | None | None | None | None | I | None | 0 | 1.69745E-05 | None | 0 | 2.43487E-05 | None | 0 | 0 | 2.39459E-06 | 0 | 2.84803E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6417 | likely_pathogenic | 0.6424 | pathogenic | -2.081 | Highly Destabilizing | 0.004 | N | 0.227 | neutral | None | None | None | None | I |
| I/C | 0.7357 | likely_pathogenic | 0.7309 | pathogenic | -1.41 | Destabilizing | 0.987 | D | 0.419 | neutral | None | None | None | None | I |
| I/D | 0.9751 | likely_pathogenic | 0.9733 | pathogenic | -1.699 | Destabilizing | 0.953 | D | 0.521 | neutral | None | None | None | None | I |
| I/E | 0.9345 | likely_pathogenic | 0.9324 | pathogenic | -1.589 | Destabilizing | 0.91 | D | 0.529 | neutral | None | None | None | None | I |
| I/F | 0.3931 | ambiguous | 0.4074 | ambiguous | -1.266 | Destabilizing | 0.91 | D | 0.444 | neutral | None | None | None | None | I |
| I/G | 0.905 | likely_pathogenic | 0.9004 | pathogenic | -2.516 | Highly Destabilizing | 0.59 | D | 0.515 | neutral | None | None | None | None | I |
| I/H | 0.888 | likely_pathogenic | 0.8863 | pathogenic | -1.774 | Destabilizing | 0.996 | D | 0.491 | neutral | None | None | None | None | I |
| I/K | 0.8536 | likely_pathogenic | 0.8518 | pathogenic | -1.549 | Destabilizing | 0.884 | D | 0.527 | neutral | N | 0.501029242 | None | None | I |
| I/L | 0.1446 | likely_benign | 0.14 | benign | -0.897 | Destabilizing | 0.164 | N | 0.325 | neutral | N | 0.494386513 | None | None | I |
| I/M | 0.1775 | likely_benign | 0.1748 | benign | -0.803 | Destabilizing | 0.939 | D | 0.445 | neutral | N | 0.496901412 | None | None | I |
| I/N | 0.7569 | likely_pathogenic | 0.738 | pathogenic | -1.577 | Destabilizing | 0.953 | D | 0.515 | neutral | None | None | None | None | I |
| I/P | 0.9776 | likely_pathogenic | 0.9768 | pathogenic | -1.265 | Destabilizing | 0.953 | D | 0.509 | neutral | None | None | None | None | I |
| I/Q | 0.8406 | likely_pathogenic | 0.8342 | pathogenic | -1.61 | Destabilizing | 0.953 | D | 0.511 | neutral | None | None | None | None | I |
| I/R | 0.7916 | likely_pathogenic | 0.7893 | pathogenic | -1.081 | Destabilizing | 0.939 | D | 0.515 | neutral | N | 0.505548693 | None | None | I |
| I/S | 0.7134 | likely_pathogenic | 0.6985 | pathogenic | -2.286 | Highly Destabilizing | 0.59 | D | 0.426 | neutral | None | None | None | None | I |
| I/T | 0.495 | ambiguous | 0.4886 | ambiguous | -2.047 | Highly Destabilizing | 0.684 | D | 0.387 | neutral | N | 0.49292494 | None | None | I |
| I/V | 0.0702 | likely_benign | 0.0712 | benign | -1.265 | Destabilizing | 0.003 | N | 0.173 | neutral | N | 0.400662701 | None | None | I |
| I/W | 0.9498 | likely_pathogenic | 0.9514 | pathogenic | -1.47 | Destabilizing | 0.996 | D | 0.561 | neutral | None | None | None | None | I |
| I/Y | 0.8194 | likely_pathogenic | 0.8256 | pathogenic | -1.21 | Destabilizing | 0.953 | D | 0.431 | 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.