Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25982 | 78169;78170;78171 | chr2:178568188;178568187;178568186 | chr2:179432915;179432914;179432913 |
| N2AB | 24341 | 73246;73247;73248 | chr2:178568188;178568187;178568186 | chr2:179432915;179432914;179432913 |
| N2A | 23414 | 70465;70466;70467 | chr2:178568188;178568187;178568186 | chr2:179432915;179432914;179432913 |
| N2B | 16917 | 50974;50975;50976 | chr2:178568188;178568187;178568186 | chr2:179432915;179432914;179432913 |
| Novex-1 | 17042 | 51349;51350;51351 | chr2:178568188;178568187;178568186 | chr2:179432915;179432914;179432913 |
| Novex-2 | 17109 | 51550;51551;51552 | chr2:178568188;178568187;178568186 | chr2:179432915;179432914;179432913 |
| 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/N | rs760050553  |
None | 0.162 | N | 0.599 | 0.363 | 0.724408429609 | gnomAD-4.0.0 | 6.84291E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73551E-04 | 0 | 0 | 0 |
| I/T | rs760050553 |
-2.089 | 0.006 | N | 0.378 | 0.287 | 0.638618496958 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/T | rs760050553 |
-2.089 | 0.006 | N | 0.378 | 0.287 | 0.638618496958 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs760050553 |
-2.089 | 0.006 | N | 0.378 | 0.287 | 0.638618496958 | gnomAD-4.0.0 | 1.05367E-05 | None | None | None | None | N | None | 6.67967E-05 | 0 | None | 0 | 6.68777E-05 | None | 0 | 0 | 4.23876E-06 | 4.39165E-05 | 0 |
| I/V | None | None | None | N | 0.115 | 0.06 | 0.151104730317 | gnomAD-4.0.0 | 1.59171E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77331E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2225 | likely_benign | 0.2495 | benign | -2.221 | Highly Destabilizing | 0.003 | N | 0.364 | neutral | None | None | None | None | N |
| I/C | 0.5784 | likely_pathogenic | 0.5602 | ambiguous | -1.445 | Destabilizing | 0.204 | N | 0.429 | neutral | None | None | None | None | N |
| I/D | 0.8972 | likely_pathogenic | 0.918 | pathogenic | -2.595 | Highly Destabilizing | 0.204 | N | 0.604 | neutral | None | None | None | None | N |
| I/E | 0.6861 | likely_pathogenic | 0.7332 | pathogenic | -2.356 | Highly Destabilizing | 0.068 | N | 0.582 | neutral | None | None | None | None | N |
| I/F | 0.2281 | likely_benign | 0.2369 | benign | -1.372 | Destabilizing | 0.026 | N | 0.422 | neutral | N | 0.514438419 | None | None | N |
| I/G | 0.7547 | likely_pathogenic | 0.78 | pathogenic | -2.73 | Highly Destabilizing | 0.068 | N | 0.562 | neutral | None | None | None | None | N |
| I/H | 0.6801 | likely_pathogenic | 0.6921 | pathogenic | -2.031 | Highly Destabilizing | 0.747 | D | 0.597 | neutral | None | None | None | None | N |
| I/K | 0.5054 | ambiguous | 0.5262 | ambiguous | -1.762 | Destabilizing | 0.035 | N | 0.574 | neutral | None | None | None | None | N |
| I/L | 0.1307 | likely_benign | 0.1311 | benign | -0.747 | Destabilizing | None | N | 0.125 | neutral | N | 0.47510924 | None | None | N |
| I/M | 0.1003 | likely_benign | 0.1059 | benign | -0.653 | Destabilizing | 0.001 | N | 0.273 | neutral | N | 0.464656834 | None | None | N |
| I/N | 0.6187 | likely_pathogenic | 0.66 | pathogenic | -2.245 | Highly Destabilizing | 0.162 | N | 0.599 | neutral | N | 0.500954249 | None | None | N |
| I/P | 0.9617 | likely_pathogenic | 0.9696 | pathogenic | -1.221 | Destabilizing | 0.439 | N | 0.608 | neutral | None | None | None | None | N |
| I/Q | 0.5364 | ambiguous | 0.5645 | pathogenic | -2.075 | Highly Destabilizing | 0.204 | N | 0.599 | neutral | None | None | None | None | N |
| I/R | 0.4327 | ambiguous | 0.4533 | ambiguous | -1.553 | Destabilizing | 0.204 | N | 0.596 | neutral | None | None | None | None | N |
| I/S | 0.4127 | ambiguous | 0.4476 | ambiguous | -2.866 | Highly Destabilizing | 0.026 | N | 0.517 | neutral | N | 0.497912375 | None | None | N |
| I/T | 0.1413 | likely_benign | 0.1562 | benign | -2.473 | Highly Destabilizing | 0.006 | N | 0.378 | neutral | N | 0.475960233 | None | None | N |
| I/V | 0.0458 | likely_benign | 0.0452 | benign | -1.221 | Destabilizing | None | N | 0.115 | neutral | N | 0.381332287 | None | None | N |
| I/W | 0.8967 | likely_pathogenic | 0.9046 | pathogenic | -1.689 | Destabilizing | 0.747 | D | 0.642 | neutral | None | None | None | None | N |
| I/Y | 0.6964 | likely_pathogenic | 0.7079 | pathogenic | -1.363 | Destabilizing | 0.204 | N | 0.517 | 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.