Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28380 | 85363;85364;85365 | chr2:178560994;178560993;178560992 | chr2:179425721;179425720;179425719 |
| N2AB | 26739 | 80440;80441;80442 | chr2:178560994;178560993;178560992 | chr2:179425721;179425720;179425719 |
| N2A | 25812 | 77659;77660;77661 | chr2:178560994;178560993;178560992 | chr2:179425721;179425720;179425719 |
| N2B | 19315 | 58168;58169;58170 | chr2:178560994;178560993;178560992 | chr2:179425721;179425720;179425719 |
| Novex-1 | 19440 | 58543;58544;58545 | chr2:178560994;178560993;178560992 | chr2:179425721;179425720;179425719 |
| Novex-2 | 19507 | 58744;58745;58746 | chr2:178560994;178560993;178560992 | chr2:179425721;179425720;179425719 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | None | None | 0.997 | N | 0.685 | 0.418 | 0.402326594622 | gnomAD-4.0.0 | 6.84193E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99449E-07 | 0 | 0 |
| D/N | rs1703440197  |
None | 0.904 | N | 0.549 | 0.308 | 0.322510055762 | gnomAD-4.0.0 | 6.84193E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99449E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3122 | likely_benign | 0.3028 | benign | -0.281 | Destabilizing | 0.822 | D | 0.649 | neutral | N | 0.482668009 | None | None | N |
| D/C | 0.8115 | likely_pathogenic | 0.8145 | pathogenic | -0.095 | Destabilizing | 0.998 | D | 0.769 | deleterious | None | None | None | None | N |
| D/E | 0.3479 | ambiguous | 0.3575 | ambiguous | -0.612 | Destabilizing | 0.025 | N | 0.242 | neutral | N | 0.468063916 | None | None | N |
| D/F | 0.762 | likely_pathogenic | 0.7657 | pathogenic | -0.335 | Destabilizing | 0.956 | D | 0.778 | deleterious | None | None | None | None | N |
| D/G | 0.3542 | ambiguous | 0.3327 | benign | -0.551 | Destabilizing | 0.904 | D | 0.623 | neutral | N | 0.50920125 | None | None | N |
| D/H | 0.4451 | ambiguous | 0.4425 | ambiguous | -0.749 | Destabilizing | 0.997 | D | 0.685 | prob.neutral | N | 0.520975681 | None | None | N |
| D/I | 0.5342 | ambiguous | 0.5608 | ambiguous | 0.401 | Stabilizing | 0.043 | N | 0.561 | neutral | None | None | None | None | N |
| D/K | 0.617 | likely_pathogenic | 0.642 | pathogenic | -0.576 | Destabilizing | 0.86 | D | 0.631 | neutral | None | None | None | None | N |
| D/L | 0.5764 | likely_pathogenic | 0.5892 | pathogenic | 0.401 | Stabilizing | 0.514 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/M | 0.7709 | likely_pathogenic | 0.7696 | pathogenic | 0.742 | Stabilizing | 0.988 | D | 0.767 | deleterious | None | None | None | None | N |
| D/N | 0.1745 | likely_benign | 0.1617 | benign | -0.599 | Destabilizing | 0.904 | D | 0.549 | neutral | N | 0.517319301 | None | None | N |
| D/P | 0.9307 | likely_pathogenic | 0.9475 | pathogenic | 0.198 | Stabilizing | 0.993 | D | 0.709 | prob.delet. | None | None | None | None | N |
| D/Q | 0.5602 | ambiguous | 0.5649 | pathogenic | -0.506 | Destabilizing | 0.956 | D | 0.575 | neutral | None | None | None | None | N |
| D/R | 0.6099 | likely_pathogenic | 0.6279 | pathogenic | -0.49 | Destabilizing | 0.956 | D | 0.733 | prob.delet. | None | None | None | None | N |
| D/S | 0.2289 | likely_benign | 0.2196 | benign | -0.809 | Destabilizing | 0.86 | D | 0.501 | neutral | None | None | None | None | N |
| D/T | 0.4154 | ambiguous | 0.4235 | ambiguous | -0.622 | Destabilizing | 0.86 | D | 0.638 | neutral | None | None | None | None | N |
| D/V | 0.3387 | likely_benign | 0.3468 | ambiguous | 0.198 | Stabilizing | 0.443 | N | 0.687 | prob.neutral | N | 0.513510991 | None | None | N |
| D/W | 0.9393 | likely_pathogenic | 0.9377 | pathogenic | -0.368 | Destabilizing | 0.998 | D | 0.742 | deleterious | None | None | None | None | N |
| D/Y | 0.3476 | ambiguous | 0.3334 | benign | -0.198 | Destabilizing | 0.97 | D | 0.777 | deleterious | N | 0.483592869 | 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.