Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24871 | 74836;74837;74838 | chr2:178571521;178571520;178571519 | chr2:179436248;179436247;179436246 |
| N2AB | 23230 | 69913;69914;69915 | chr2:178571521;178571520;178571519 | chr2:179436248;179436247;179436246 |
| N2A | 22303 | 67132;67133;67134 | chr2:178571521;178571520;178571519 | chr2:179436248;179436247;179436246 |
| N2B | 15806 | 47641;47642;47643 | chr2:178571521;178571520;178571519 | chr2:179436248;179436247;179436246 |
| Novex-1 | 15931 | 48016;48017;48018 | chr2:178571521;178571520;178571519 | chr2:179436248;179436247;179436246 |
| Novex-2 | 15998 | 48217;48218;48219 | chr2:178571521;178571520;178571519 | chr2:179436248;179436247;179436246 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/G | rs1277175098  |
-1.367 | 0.028 | N | 0.354 | 0.13 | 0.276898752692 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| C/G | rs1277175098 |
-1.367 | 0.028 | N | 0.354 | 0.13 | 0.276898752692 | gnomAD-4.0.0 | 1.59239E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85958E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.2003 | likely_benign | 0.1629 | benign | -1.244 | Destabilizing | 0.001 | N | 0.078 | neutral | None | None | None | None | N |
| C/D | 0.7314 | likely_pathogenic | 0.7226 | pathogenic | 0.143 | Stabilizing | 0.148 | N | 0.41 | neutral | None | None | None | None | N |
| C/E | 0.8054 | likely_pathogenic | 0.789 | pathogenic | 0.151 | Stabilizing | 0.08 | N | 0.37 | neutral | None | None | None | None | N |
| C/F | 0.1552 | likely_benign | 0.1605 | benign | -0.932 | Destabilizing | 0.391 | N | 0.557 | neutral | N | 0.434420197 | None | None | N |
| C/G | 0.0871 | likely_benign | 0.0884 | benign | -1.455 | Destabilizing | 0.028 | N | 0.354 | neutral | N | 0.351919031 | None | None | N |
| C/H | 0.4835 | ambiguous | 0.4818 | ambiguous | -1.403 | Destabilizing | 0.001 | N | 0.425 | neutral | None | None | None | None | N |
| C/I | 0.3369 | likely_benign | 0.3225 | benign | -0.749 | Destabilizing | 0.148 | N | 0.445 | neutral | None | None | None | None | N |
| C/K | 0.7931 | likely_pathogenic | 0.7755 | pathogenic | -0.459 | Destabilizing | 0.08 | N | 0.375 | neutral | None | None | None | None | N |
| C/L | 0.2474 | likely_benign | 0.2534 | benign | -0.749 | Destabilizing | 0.036 | N | 0.267 | neutral | None | None | None | None | N |
| C/M | 0.3573 | ambiguous | 0.3392 | benign | -0.084 | Destabilizing | 0.901 | D | 0.442 | neutral | None | None | None | None | N |
| C/N | 0.3041 | likely_benign | 0.2881 | benign | -0.138 | Destabilizing | 0.08 | N | 0.434 | neutral | None | None | None | None | N |
| C/P | 0.4808 | ambiguous | 0.4045 | ambiguous | -0.889 | Destabilizing | 0.46 | N | 0.529 | neutral | None | None | None | None | N |
| C/Q | 0.5597 | ambiguous | 0.5352 | ambiguous | -0.257 | Destabilizing | 0.296 | N | 0.554 | neutral | None | None | None | None | N |
| C/R | 0.5711 | likely_pathogenic | 0.5547 | ambiguous | -0.122 | Destabilizing | 0.241 | N | 0.534 | neutral | N | 0.385626173 | None | None | N |
| C/S | 0.129 | likely_benign | 0.1119 | benign | -0.686 | Destabilizing | None | N | 0.15 | neutral | N | 0.326231153 | None | None | N |
| C/T | 0.2099 | likely_benign | 0.1819 | benign | -0.53 | Destabilizing | 0.001 | N | 0.141 | neutral | None | None | None | None | N |
| C/V | 0.2563 | likely_benign | 0.239 | benign | -0.889 | Destabilizing | 0.036 | N | 0.283 | neutral | None | None | None | None | N |
| C/W | 0.4662 | ambiguous | 0.4714 | ambiguous | -0.831 | Destabilizing | 0.963 | D | 0.497 | neutral | N | 0.477960331 | None | None | N |
| C/Y | 0.2507 | likely_benign | 0.2521 | benign | -0.795 | Destabilizing | 0.137 | N | 0.519 | neutral | N | 0.434420197 | 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.