Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21990 | 66193;66194;66195 | chr2:178582488;178582487;178582486 | chr2:179447215;179447214;179447213 |
| N2AB | 20349 | 61270;61271;61272 | chr2:178582488;178582487;178582486 | chr2:179447215;179447214;179447213 |
| N2A | 19422 | 58489;58490;58491 | chr2:178582488;178582487;178582486 | chr2:179447215;179447214;179447213 |
| N2B | 12925 | 38998;38999;39000 | chr2:178582488;178582487;178582486 | chr2:179447215;179447214;179447213 |
| Novex-1 | 13050 | 39373;39374;39375 | chr2:178582488;178582487;178582486 | chr2:179447215;179447214;179447213 |
| Novex-2 | 13117 | 39574;39575;39576 | chr2:178582488;178582487;178582486 | chr2:179447215;179447214;179447213 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs1356541458  |
-1.795 | 0.998 | N | 0.477 | 0.402 | 0.336892272479 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14837E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/D | rs1356541458 |
-1.795 | 0.998 | N | 0.477 | 0.402 | 0.336892272479 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/D | rs1356541458 |
-1.795 | 0.998 | N | 0.477 | 0.402 | 0.336892272479 | gnomAD-4.0.0 | 1.86013E-06 | None | None | None | None | N | None | 2.67194E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.09854E-05 | 0 |
| N/K | None | None | 0.999 | N | 0.604 | 0.297 | 0.184867976434 | gnomAD-4.0.0 | 1.20038E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31257E-06 | 0 | 0 |
| N/Y | None | None | 1.0 | N | 0.825 | 0.451 | 0.45746916685 | gnomAD-4.0.0 | 6.84599E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99834E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.753 | likely_pathogenic | 0.7053 | pathogenic | -0.961 | Destabilizing | 0.997 | D | 0.591 | neutral | None | None | None | None | N |
| N/C | 0.5117 | ambiguous | 0.4541 | ambiguous | -0.308 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| N/D | 0.6871 | likely_pathogenic | 0.6964 | pathogenic | -1.328 | Destabilizing | 0.998 | D | 0.477 | neutral | N | 0.470875032 | None | None | N |
| N/E | 0.9644 | likely_pathogenic | 0.95 | pathogenic | -1.184 | Destabilizing | 1.0 | D | 0.549 | neutral | None | None | None | None | N |
| N/F | 0.9486 | likely_pathogenic | 0.9195 | pathogenic | -0.694 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| N/G | 0.4841 | ambiguous | 0.467 | ambiguous | -1.317 | Destabilizing | 0.504 | D | 0.311 | neutral | None | None | None | None | N |
| N/H | 0.2025 | likely_benign | 0.1857 | benign | -0.979 | Destabilizing | 1.0 | D | 0.647 | neutral | N | 0.47236251 | None | None | N |
| N/I | 0.9802 | likely_pathogenic | 0.9676 | pathogenic | -0.039 | Destabilizing | 1.0 | D | 0.85 | deleterious | N | 0.486372394 | None | None | N |
| N/K | 0.9207 | likely_pathogenic | 0.8951 | pathogenic | -0.276 | Destabilizing | 0.999 | D | 0.604 | neutral | N | 0.508955241 | None | None | N |
| N/L | 0.9415 | likely_pathogenic | 0.9119 | pathogenic | -0.039 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| N/M | 0.9615 | likely_pathogenic | 0.94 | pathogenic | 0.391 | Stabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| N/P | 0.9979 | likely_pathogenic | 0.9974 | pathogenic | -0.317 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| N/Q | 0.8662 | likely_pathogenic | 0.8319 | pathogenic | -1.049 | Destabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| N/R | 0.8086 | likely_pathogenic | 0.7638 | pathogenic | -0.292 | Destabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | N |
| N/S | 0.141 | likely_benign | 0.1441 | benign | -1.088 | Destabilizing | 0.996 | D | 0.443 | neutral | N | 0.457238342 | None | None | N |
| N/T | 0.7861 | likely_pathogenic | 0.7336 | pathogenic | -0.754 | Destabilizing | 0.998 | D | 0.54 | neutral | N | 0.467000692 | None | None | N |
| N/V | 0.9562 | likely_pathogenic | 0.931 | pathogenic | -0.317 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| N/W | 0.9726 | likely_pathogenic | 0.9623 | pathogenic | -0.474 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| N/Y | 0.6147 | likely_pathogenic | 0.5247 | ambiguous | -0.198 | Destabilizing | 1.0 | D | 0.825 | deleterious | N | 0.502434701 | 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.