Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25005 | 75238;75239;75240 | chr2:178571119;178571118;178571117 | chr2:179435846;179435845;179435844 |
| N2AB | 23364 | 70315;70316;70317 | chr2:178571119;178571118;178571117 | chr2:179435846;179435845;179435844 |
| N2A | 22437 | 67534;67535;67536 | chr2:178571119;178571118;178571117 | chr2:179435846;179435845;179435844 |
| N2B | 15940 | 48043;48044;48045 | chr2:178571119;178571118;178571117 | chr2:179435846;179435845;179435844 |
| Novex-1 | 16065 | 48418;48419;48420 | chr2:178571119;178571118;178571117 | chr2:179435846;179435845;179435844 |
| Novex-2 | 16132 | 48619;48620;48621 | chr2:178571119;178571118;178571117 | chr2:179435846;179435845;179435844 |
| 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/A | rs761496228  |
0.274 | 0.841 | N | 0.581 | 0.327 | 0.326881540566 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/A | rs761496228 |
0.274 | 0.841 | N | 0.581 | 0.327 | 0.326881540566 | gnomAD-4.0.0 | 1.59194E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43291E-05 | 0 |
| D/E | rs2154169091 |
None | 0.955 | N | 0.503 | 0.114 | 0.211220785272 | gnomAD-4.0.0 | 1.59203E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88565E-05 | 0 | 0 | 0 | 0 |
| D/N | rs766883705 |
0.545 | 0.974 | N | 0.771 | 0.334 | 0.322510055762 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65948E-04 |
| D/N | rs766883705 |
0.545 | 0.974 | N | 0.771 | 0.334 | 0.322510055762 | gnomAD-4.0.0 | 1.59203E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77516E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.6993 | likely_pathogenic | 0.6973 | pathogenic | -0.368 | Destabilizing | 0.841 | D | 0.581 | neutral | N | 0.46161496 | None | None | N |
| D/C | 0.9596 | likely_pathogenic | 0.9577 | pathogenic | 0.019 | Stabilizing | 0.999 | D | 0.85 | deleterious | None | None | None | None | N |
| D/E | 0.6142 | likely_pathogenic | 0.6313 | pathogenic | -0.346 | Destabilizing | 0.955 | D | 0.503 | neutral | N | 0.509184528 | None | None | N |
| D/F | 0.9184 | likely_pathogenic | 0.9204 | pathogenic | -0.374 | Destabilizing | 0.999 | D | 0.788 | deleterious | None | None | None | None | N |
| D/G | 0.804 | likely_pathogenic | 0.7942 | pathogenic | -0.549 | Destabilizing | 0.032 | N | 0.378 | neutral | N | 0.470680314 | None | None | N |
| D/H | 0.7966 | likely_pathogenic | 0.7932 | pathogenic | -0.217 | Destabilizing | 0.999 | D | 0.827 | deleterious | N | 0.485331983 | None | None | N |
| D/I | 0.8776 | likely_pathogenic | 0.8818 | pathogenic | 0.057 | Stabilizing | 0.997 | D | 0.796 | deleterious | None | None | None | None | N |
| D/K | 0.928 | likely_pathogenic | 0.9291 | pathogenic | 0.267 | Stabilizing | 0.98 | D | 0.798 | deleterious | None | None | None | None | N |
| D/L | 0.8189 | likely_pathogenic | 0.8261 | pathogenic | 0.057 | Stabilizing | 0.99 | D | 0.711 | prob.delet. | None | None | None | None | N |
| D/M | 0.9431 | likely_pathogenic | 0.9466 | pathogenic | 0.238 | Stabilizing | 0.999 | D | 0.853 | deleterious | None | None | None | None | N |
| D/N | 0.3256 | likely_benign | 0.3366 | benign | 0.001 | Stabilizing | 0.974 | D | 0.771 | deleterious | N | 0.470568636 | None | None | N |
| D/P | 0.9605 | likely_pathogenic | 0.9552 | pathogenic | -0.063 | Destabilizing | 0.997 | D | 0.78 | deleterious | None | None | None | None | N |
| D/Q | 0.8813 | likely_pathogenic | 0.8807 | pathogenic | 0.019 | Stabilizing | 0.997 | D | 0.793 | deleterious | None | None | None | None | N |
| D/R | 0.9422 | likely_pathogenic | 0.9404 | pathogenic | 0.405 | Stabilizing | 0.99 | D | 0.785 | deleterious | None | None | None | None | N |
| D/S | 0.4779 | ambiguous | 0.4718 | ambiguous | -0.103 | Destabilizing | 0.933 | D | 0.723 | deleterious | None | None | None | None | N |
| D/T | 0.8129 | likely_pathogenic | 0.8072 | pathogenic | 0.037 | Stabilizing | 0.99 | D | 0.801 | deleterious | None | None | None | None | N |
| D/V | 0.7644 | likely_pathogenic | 0.7712 | pathogenic | -0.063 | Destabilizing | 0.987 | D | 0.72 | deleterious | N | 0.484522289 | None | None | N |
| D/W | 0.9866 | likely_pathogenic | 0.9873 | pathogenic | -0.25 | Destabilizing | 0.999 | D | 0.843 | deleterious | None | None | None | None | N |
| D/Y | 0.6331 | likely_pathogenic | 0.6293 | pathogenic | -0.144 | Destabilizing | 0.999 | D | 0.803 | deleterious | N | 0.487484803 | 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.