Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25906 | 77941;77942;77943 | chr2:178568416;178568415;178568414 | chr2:179433143;179433142;179433141 |
| N2AB | 24265 | 73018;73019;73020 | chr2:178568416;178568415;178568414 | chr2:179433143;179433142;179433141 |
| N2A | 23338 | 70237;70238;70239 | chr2:178568416;178568415;178568414 | chr2:179433143;179433142;179433141 |
| N2B | 16841 | 50746;50747;50748 | chr2:178568416;178568415;178568414 | chr2:179433143;179433142;179433141 |
| Novex-1 | 16966 | 51121;51122;51123 | chr2:178568416;178568415;178568414 | chr2:179433143;179433142;179433141 |
| Novex-2 | 17033 | 51322;51323;51324 | chr2:178568416;178568415;178568414 | chr2:179433143;179433142;179433141 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/K | rs56341835  |
0.456 | 0.999 | N | 0.577 | 0.348 | None | gnomAD-2.1.1 | 5.61713E-04 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 5.18E-05 | None | 0 | None | 3.60664E-04 | 1.11101E-03 | 4.23012E-04 |
| E/K | rs56341835 |
0.456 | 0.999 | N | 0.577 | 0.348 | None | gnomAD-3.1.2 | 5.91895E-04 | None | None | None | None | N | None | 1.20691E-04 | 0 | 0 | 0 | 0 | None | 2.82592E-04 | 0 | 1.20609E-03 | 0 | 0 |
| E/K | rs56341835 |
0.456 | 0.999 | N | 0.577 | 0.348 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| E/K | rs56341835 |
0.456 | 0.999 | N | 0.577 | 0.348 | None | gnomAD-4.0.0 | 8.38711E-04 | None | None | None | None | N | None | 1.46682E-04 | 1.66872E-05 | None | 0 | 2.23674E-05 | None | 5.47354E-04 | 0 | 1.07413E-03 | 0 | 6.08604E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.2706 | likely_benign | 0.2605 | benign | -0.627 | Destabilizing | 0.999 | D | 0.649 | neutral | N | 0.506667085 | None | None | N |
| E/C | 0.9222 | likely_pathogenic | 0.9094 | pathogenic | 0.097 | Stabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | N |
| E/D | 0.1112 | likely_benign | 0.1096 | benign | -0.42 | Destabilizing | 0.999 | D | 0.482 | neutral | N | 0.385434172 | None | None | N |
| E/F | 0.8917 | likely_pathogenic | 0.8922 | pathogenic | -0.666 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | N |
| E/G | 0.2648 | likely_benign | 0.2649 | benign | -0.838 | Destabilizing | 1.0 | D | 0.666 | neutral | N | 0.495276655 | None | None | N |
| E/H | 0.7093 | likely_pathogenic | 0.6797 | pathogenic | -0.768 | Destabilizing | 1.0 | D | 0.597 | neutral | None | None | None | None | N |
| E/I | 0.6676 | likely_pathogenic | 0.6826 | pathogenic | -0.097 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| E/K | 0.3968 | ambiguous | 0.3917 | ambiguous | 0.245 | Stabilizing | 0.999 | D | 0.577 | neutral | N | 0.495103297 | None | None | N |
| E/L | 0.6559 | likely_pathogenic | 0.6586 | pathogenic | -0.097 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| E/M | 0.6782 | likely_pathogenic | 0.6752 | pathogenic | 0.314 | Stabilizing | 1.0 | D | 0.595 | neutral | None | None | None | None | N |
| E/N | 0.292 | likely_benign | 0.2788 | benign | -0.018 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| E/P | 0.9487 | likely_pathogenic | 0.9518 | pathogenic | -0.254 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| E/Q | 0.2732 | likely_benign | 0.2536 | benign | -0.001 | Destabilizing | 1.0 | D | 0.604 | neutral | N | 0.521212463 | None | None | N |
| E/R | 0.5882 | likely_pathogenic | 0.5733 | pathogenic | 0.259 | Stabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| E/S | 0.2574 | likely_benign | 0.246 | benign | -0.206 | Destabilizing | 0.999 | D | 0.624 | neutral | None | None | None | None | N |
| E/T | 0.2762 | likely_benign | 0.2837 | benign | -0.031 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| E/V | 0.4465 | ambiguous | 0.4477 | ambiguous | -0.254 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | N | 0.477458398 | None | None | N |
| E/W | 0.9684 | likely_pathogenic | 0.9668 | pathogenic | -0.529 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| E/Y | 0.8001 | likely_pathogenic | 0.7947 | pathogenic | -0.425 | Destabilizing | 1.0 | D | 0.633 | 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.