Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23179 | 69760;69761;69762 | chr2:178576709;178576708;178576707 | chr2:179441436;179441435;179441434 |
| N2AB | 21538 | 64837;64838;64839 | chr2:178576709;178576708;178576707 | chr2:179441436;179441435;179441434 |
| N2A | 20611 | 62056;62057;62058 | chr2:178576709;178576708;178576707 | chr2:179441436;179441435;179441434 |
| N2B | 14114 | 42565;42566;42567 | chr2:178576709;178576708;178576707 | chr2:179441436;179441435;179441434 |
| Novex-1 | 14239 | 42940;42941;42942 | chr2:178576709;178576708;178576707 | chr2:179441436;179441435;179441434 |
| Novex-2 | 14306 | 43141;43142;43143 | chr2:178576709;178576708;178576707 | chr2:179441436;179441435;179441434 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 0.117 | N | 0.519 | 0.359 | 0.385743280973 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| R/K | None | None | None | N | 0.156 | 0.102 | 0.250039746154 | gnomAD-4.0.0 | 2.73712E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 6.93963E-04 | 0 | 0 | 0 |
| R/T | rs763091757  |
-1.734 | 0.117 | N | 0.483 | 0.23 | 0.286465849087 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 5.79E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/T | rs763091757 |
-1.734 | 0.117 | N | 0.483 | 0.23 | 0.286465849087 | gnomAD-4.0.0 | 2.73712E-06 | None | None | None | None | N | None | 0 | 6.70841E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65673E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9338 | likely_pathogenic | 0.9494 | pathogenic | -1.948 | Destabilizing | 0.035 | N | 0.503 | neutral | None | None | None | None | N |
| R/C | 0.4169 | ambiguous | 0.4613 | ambiguous | -1.895 | Destabilizing | 0.935 | D | 0.649 | neutral | None | None | None | None | N |
| R/D | 0.9942 | likely_pathogenic | 0.9955 | pathogenic | -0.819 | Destabilizing | 0.149 | N | 0.566 | neutral | None | None | None | None | N |
| R/E | 0.9192 | likely_pathogenic | 0.9382 | pathogenic | -0.627 | Destabilizing | 0.035 | N | 0.545 | neutral | None | None | None | None | N |
| R/F | 0.9251 | likely_pathogenic | 0.9441 | pathogenic | -1.366 | Destabilizing | 0.791 | D | 0.638 | neutral | None | None | None | None | N |
| R/G | 0.8808 | likely_pathogenic | 0.9071 | pathogenic | -2.286 | Highly Destabilizing | 0.117 | N | 0.519 | neutral | N | 0.49712327 | None | None | N |
| R/H | 0.264 | likely_benign | 0.3047 | benign | -2.15 | Highly Destabilizing | 0.555 | D | 0.489 | neutral | None | None | None | None | N |
| R/I | 0.8801 | likely_pathogenic | 0.9146 | pathogenic | -0.979 | Destabilizing | 0.484 | N | 0.632 | neutral | N | 0.49686978 | None | None | N |
| R/K | 0.1382 | likely_benign | 0.1453 | benign | -1.451 | Destabilizing | None | N | 0.156 | neutral | N | 0.412487487 | None | None | N |
| R/L | 0.7135 | likely_pathogenic | 0.7752 | pathogenic | -0.979 | Destabilizing | 0.149 | N | 0.519 | neutral | None | None | None | None | N |
| R/M | 0.7457 | likely_pathogenic | 0.799 | pathogenic | -1.369 | Destabilizing | 0.791 | D | 0.531 | neutral | None | None | None | None | N |
| R/N | 0.9747 | likely_pathogenic | 0.9794 | pathogenic | -1.223 | Destabilizing | 0.149 | N | 0.485 | neutral | None | None | None | None | N |
| R/P | 0.9963 | likely_pathogenic | 0.9973 | pathogenic | -1.289 | Destabilizing | 0.555 | D | 0.575 | neutral | None | None | None | None | N |
| R/Q | 0.2756 | likely_benign | 0.2992 | benign | -1.23 | Destabilizing | 0.081 | N | 0.518 | neutral | None | None | None | None | N |
| R/S | 0.9726 | likely_pathogenic | 0.9779 | pathogenic | -2.196 | Highly Destabilizing | 0.062 | N | 0.497 | neutral | N | 0.520847103 | None | None | N |
| R/T | 0.9324 | likely_pathogenic | 0.9475 | pathogenic | -1.795 | Destabilizing | 0.117 | N | 0.483 | neutral | N | 0.478512036 | None | None | N |
| R/V | 0.9045 | likely_pathogenic | 0.9312 | pathogenic | -1.289 | Destabilizing | 0.38 | N | 0.607 | neutral | None | None | None | None | N |
| R/W | 0.5874 | likely_pathogenic | 0.6738 | pathogenic | -0.84 | Destabilizing | 0.935 | D | 0.68 | prob.neutral | None | None | None | None | N |
| R/Y | 0.8513 | likely_pathogenic | 0.8777 | pathogenic | -0.668 | Destabilizing | 0.791 | D | 0.606 | 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.