Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28701 | 86326;86327;86328 | chr2:178560031;178560030;178560029 | chr2:179424758;179424757;179424756 |
| N2AB | 27060 | 81403;81404;81405 | chr2:178560031;178560030;178560029 | chr2:179424758;179424757;179424756 |
| N2A | 26133 | 78622;78623;78624 | chr2:178560031;178560030;178560029 | chr2:179424758;179424757;179424756 |
| N2B | 19636 | 59131;59132;59133 | chr2:178560031;178560030;178560029 | chr2:179424758;179424757;179424756 |
| Novex-1 | 19761 | 59506;59507;59508 | chr2:178560031;178560030;178560029 | chr2:179424758;179424757;179424756 |
| Novex-2 | 19828 | 59707;59708;59709 | chr2:178560031;178560030;178560029 | chr2:179424758;179424757;179424756 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | rs769512321  |
-0.86 | 0.295 | N | 0.555 | 0.217 | 0.386395597597 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| S/F | rs769512321 |
-0.86 | 0.295 | N | 0.555 | 0.217 | 0.386395597597 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/F | rs769512321 |
-0.86 | 0.295 | N | 0.555 | 0.217 | 0.386395597597 | gnomAD-4.0.0 | 6.57384E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46998E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0428 | likely_benign | 0.0435 | benign | -0.515 | Destabilizing | None | N | 0.124 | neutral | N | 0.33725901 | None | None | N |
| S/C | 0.086 | likely_benign | 0.0854 | benign | -0.286 | Destabilizing | 0.295 | N | 0.503 | neutral | N | 0.385610317 | None | None | N |
| S/D | 0.4273 | ambiguous | 0.4487 | ambiguous | 0.11 | Stabilizing | 0.031 | N | 0.337 | neutral | None | None | None | None | N |
| S/E | 0.498 | ambiguous | 0.52 | ambiguous | 0.198 | Stabilizing | 0.031 | N | 0.351 | neutral | None | None | None | None | N |
| S/F | 0.2272 | likely_benign | 0.2582 | benign | -0.741 | Destabilizing | 0.295 | N | 0.555 | neutral | N | 0.420624181 | None | None | N |
| S/G | 0.0781 | likely_benign | 0.0757 | benign | -0.803 | Destabilizing | None | N | 0.138 | neutral | None | None | None | None | N |
| S/H | 0.4142 | ambiguous | 0.4287 | ambiguous | -1.017 | Destabilizing | 0.628 | D | 0.501 | neutral | None | None | None | None | N |
| S/I | 0.1361 | likely_benign | 0.1487 | benign | 0.164 | Stabilizing | 0.072 | N | 0.468 | neutral | None | None | None | None | N |
| S/K | 0.7124 | likely_pathogenic | 0.7411 | pathogenic | 0.01 | Stabilizing | 0.031 | N | 0.347 | neutral | None | None | None | None | N |
| S/L | 0.1221 | likely_benign | 0.1368 | benign | 0.164 | Stabilizing | 0.016 | N | 0.444 | neutral | None | None | None | None | N |
| S/M | 0.1801 | likely_benign | 0.2014 | benign | -0.011 | Destabilizing | 0.356 | N | 0.506 | neutral | None | None | None | None | N |
| S/N | 0.198 | likely_benign | 0.2094 | benign | -0.306 | Destabilizing | 0.031 | N | 0.348 | neutral | None | None | None | None | N |
| S/P | 0.3913 | ambiguous | 0.4051 | ambiguous | -0.029 | Destabilizing | 0.055 | N | 0.467 | neutral | N | 0.482040786 | None | None | N |
| S/Q | 0.5063 | ambiguous | 0.535 | ambiguous | -0.211 | Destabilizing | 0.136 | N | 0.441 | neutral | None | None | None | None | N |
| S/R | 0.6503 | likely_pathogenic | 0.675 | pathogenic | -0.107 | Destabilizing | 0.072 | N | 0.48 | neutral | None | None | None | None | N |
| S/T | 0.0793 | likely_benign | 0.0877 | benign | -0.248 | Destabilizing | None | N | 0.143 | neutral | N | 0.428745019 | None | None | N |
| S/V | 0.1022 | likely_benign | 0.1127 | benign | -0.029 | Destabilizing | 0.016 | N | 0.445 | neutral | None | None | None | None | N |
| S/W | 0.4434 | ambiguous | 0.4961 | ambiguous | -0.865 | Destabilizing | 0.864 | D | 0.525 | neutral | None | None | None | None | N |
| S/Y | 0.2114 | likely_benign | 0.2382 | benign | -0.448 | Destabilizing | 0.295 | N | 0.549 | neutral | N | 0.443829114 | 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.