Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22001 | 66226;66227;66228 | chr2:178582455;178582454;178582453 | chr2:179447182;179447181;179447180 |
| N2AB | 20360 | 61303;61304;61305 | chr2:178582455;178582454;178582453 | chr2:179447182;179447181;179447180 |
| N2A | 19433 | 58522;58523;58524 | chr2:178582455;178582454;178582453 | chr2:179447182;179447181;179447180 |
| N2B | 12936 | 39031;39032;39033 | chr2:178582455;178582454;178582453 | chr2:179447182;179447181;179447180 |
| Novex-1 | 13061 | 39406;39407;39408 | chr2:178582455;178582454;178582453 | chr2:179447182;179447181;179447180 |
| Novex-2 | 13128 | 39607;39608;39609 | chr2:178582455;178582454;178582453 | chr2:179447182;179447181;179447180 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs777788378  |
-0.171 | 0.08 | N | 0.282 | 0.266 | 0.39300627 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.63E-05 | None | 0 | None | 0 | 0 | 0 |
| P/L | rs777788378 |
-0.171 | 0.08 | N | 0.282 | 0.266 | 0.39300627 | gnomAD-4.0.0 | 6.84554E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53113E-05 | None | 0 | 0 | 0 | 0 | 0 |
| P/R | rs777788378 |
None | 0.81 | N | 0.294 | 0.351 | 0.37970752 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 6.32911E-03 | 0 | 0 | 0 |
| P/R | rs777788378 |
None | 0.81 | N | 0.294 | 0.351 | 0.37970752 | gnomAD-4.0.0 | 1.85998E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.30251E-04 | 8.47909E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1169 | likely_benign | 0.1485 | benign | -0.374 | Destabilizing | 0.001 | N | 0.139 | neutral | N | 0.41033262 | None | None | N |
| P/C | 0.8261 | likely_pathogenic | 0.8314 | pathogenic | -0.56 | Destabilizing | 0.977 | D | 0.28 | neutral | None | None | None | None | N |
| P/D | 0.857 | likely_pathogenic | 0.8358 | pathogenic | -0.313 | Destabilizing | 0.766 | D | 0.284 | neutral | None | None | None | None | N |
| P/E | 0.6506 | likely_pathogenic | 0.6168 | pathogenic | -0.423 | Destabilizing | 0.617 | D | 0.255 | neutral | None | None | None | None | N |
| P/F | 0.8648 | likely_pathogenic | 0.8608 | pathogenic | -0.635 | Destabilizing | 0.85 | D | 0.302 | neutral | None | None | None | None | N |
| P/G | 0.5804 | likely_pathogenic | 0.5953 | pathogenic | -0.49 | Destabilizing | 0.25 | N | 0.274 | neutral | None | None | None | None | N |
| P/H | 0.643 | likely_pathogenic | 0.5791 | pathogenic | -0.04 | Destabilizing | 0.009 | N | 0.259 | neutral | N | 0.4858118 | None | None | N |
| P/I | 0.5747 | likely_pathogenic | 0.5458 | ambiguous | -0.214 | Destabilizing | 0.447 | N | 0.338 | neutral | None | None | None | None | N |
| P/K | 0.7095 | likely_pathogenic | 0.647 | pathogenic | -0.369 | Destabilizing | 0.617 | D | 0.263 | neutral | None | None | None | None | N |
| P/L | 0.2865 | likely_benign | 0.2658 | benign | -0.214 | Destabilizing | 0.08 | N | 0.282 | neutral | N | 0.38599432 | None | None | N |
| P/M | 0.5289 | ambiguous | 0.5156 | ambiguous | -0.405 | Destabilizing | 0.127 | N | 0.286 | neutral | None | None | None | None | N |
| P/N | 0.7031 | likely_pathogenic | 0.6814 | pathogenic | -0.084 | Destabilizing | 0.85 | D | 0.297 | neutral | None | None | None | None | N |
| P/Q | 0.4293 | ambiguous | 0.386 | ambiguous | -0.316 | Destabilizing | 0.92 | D | 0.276 | neutral | None | None | None | None | N |
| P/R | 0.5975 | likely_pathogenic | 0.5353 | ambiguous | 0.126 | Stabilizing | 0.81 | D | 0.294 | neutral | N | 0.4135463 | None | None | N |
| P/S | 0.3553 | ambiguous | 0.3571 | ambiguous | -0.413 | Destabilizing | 0.201 | N | 0.293 | neutral | N | 0.41745058 | None | None | N |
| P/T | 0.28 | likely_benign | 0.268 | benign | -0.424 | Destabilizing | 0.549 | D | 0.275 | neutral | N | 0.439442 | None | None | N |
| P/V | 0.4072 | ambiguous | 0.3958 | ambiguous | -0.235 | Destabilizing | 0.447 | N | 0.282 | neutral | None | None | None | None | N |
| P/W | 0.9337 | likely_pathogenic | 0.9208 | pathogenic | -0.717 | Destabilizing | 0.992 | D | 0.331 | neutral | None | None | None | None | N |
| P/Y | 0.8338 | likely_pathogenic | 0.8114 | pathogenic | -0.418 | Destabilizing | 0.85 | D | 0.301 | neutral | 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.