Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31376 | 94351;94352;94353 | chr2:178547500;178547499;178547498 | chr2:179412227;179412226;179412225 |
| N2AB | 29735 | 89428;89429;89430 | chr2:178547500;178547499;178547498 | chr2:179412227;179412226;179412225 |
| N2A | 28808 | 86647;86648;86649 | chr2:178547500;178547499;178547498 | chr2:179412227;179412226;179412225 |
| N2B | 22311 | 67156;67157;67158 | chr2:178547500;178547499;178547498 | chr2:179412227;179412226;179412225 |
| Novex-1 | 22436 | 67531;67532;67533 | chr2:178547500;178547499;178547498 | chr2:179412227;179412226;179412225 |
| Novex-2 | 22503 | 67732;67733;67734 | chr2:178547500;178547499;178547498 | chr2:179412227;179412226;179412225 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | None | None | 1.0 | N | 0.794 | 0.483 | 0.654164466603 | gnomAD-4.0.0 | 1.59235E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85927E-06 | 0 | 0 |
| Y/H | rs1434130834  |
None | 1.0 | N | 0.731 | 0.451 | 0.479056812784 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Y/H | rs1434130834 |
None | 1.0 | N | 0.731 | 0.451 | 0.479056812784 | gnomAD-4.0.0 | 1.8595E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54301E-06 | 0 | 0 |
| Y/N | None | None | 1.0 | N | 0.785 | 0.482 | 0.528210255337 | gnomAD-4.0.0 | 2.73753E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.5982E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.7606 | likely_pathogenic | 0.7715 | pathogenic | -1.094 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| Y/C | 0.3491 | ambiguous | 0.3897 | ambiguous | -0.11 | Destabilizing | 1.0 | D | 0.794 | deleterious | N | 0.467850066 | None | None | N |
| Y/D | 0.3855 | ambiguous | 0.461 | ambiguous | 0.258 | Stabilizing | 1.0 | D | 0.778 | deleterious | N | 0.406156161 | None | None | N |
| Y/E | 0.8222 | likely_pathogenic | 0.8589 | pathogenic | 0.263 | Stabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| Y/F | 0.1525 | likely_benign | 0.1594 | benign | -0.511 | Destabilizing | 0.999 | D | 0.543 | neutral | N | 0.439578088 | None | None | N |
| Y/G | 0.3657 | ambiguous | 0.412 | ambiguous | -1.32 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| Y/H | 0.371 | ambiguous | 0.4149 | ambiguous | -0.079 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.469975566 | None | None | N |
| Y/I | 0.8797 | likely_pathogenic | 0.8966 | pathogenic | -0.483 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| Y/K | 0.8154 | likely_pathogenic | 0.8429 | pathogenic | -0.222 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| Y/L | 0.6941 | likely_pathogenic | 0.7281 | pathogenic | -0.483 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | N |
| Y/M | 0.8109 | likely_pathogenic | 0.8322 | pathogenic | -0.336 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| Y/N | 0.2155 | likely_benign | 0.2682 | benign | -0.474 | Destabilizing | 1.0 | D | 0.785 | deleterious | N | 0.415757079 | None | None | N |
| Y/P | 0.9546 | likely_pathogenic | 0.9621 | pathogenic | -0.671 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| Y/Q | 0.7769 | likely_pathogenic | 0.8026 | pathogenic | -0.427 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| Y/R | 0.7347 | likely_pathogenic | 0.7621 | pathogenic | 0.103 | Stabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| Y/S | 0.4549 | ambiguous | 0.4903 | ambiguous | -0.852 | Destabilizing | 1.0 | D | 0.769 | deleterious | N | 0.454544753 | None | None | N |
| Y/T | 0.7634 | likely_pathogenic | 0.781 | pathogenic | -0.755 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| Y/V | 0.7892 | likely_pathogenic | 0.8038 | pathogenic | -0.671 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| Y/W | 0.6505 | likely_pathogenic | 0.6556 | pathogenic | -0.503 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | 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.