Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1765 | 5518;5519;5520 | chr2:178776571;178776570;178776569 | chr2:179641298;179641297;179641296 |
| N2AB | 1765 | 5518;5519;5520 | chr2:178776571;178776570;178776569 | chr2:179641298;179641297;179641296 |
| N2A | 1765 | 5518;5519;5520 | chr2:178776571;178776570;178776569 | chr2:179641298;179641297;179641296 |
| N2B | 1719 | 5380;5381;5382 | chr2:178776571;178776570;178776569 | chr2:179641298;179641297;179641296 |
| Novex-1 | 1719 | 5380;5381;5382 | chr2:178776571;178776570;178776569 | chr2:179641298;179641297;179641296 |
| Novex-2 | 1719 | 5380;5381;5382 | chr2:178776571;178776570;178776569 | chr2:179641298;179641297;179641296 |
| Novex-3 | 1765 | 5518;5519;5520 | chr2:178776571;178776570;178776569 | chr2:179641298;179641297;179641296 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | None | None | None | N | 0.095 | 0.083 | 0.0666544352282 | gnomAD-4.0.0 | 6.84403E-07 | None | None | None | None | I | None | 0 | 2.23634E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| G/D | rs2092251339  |
None | None | N | 0.145 | 0.152 | 0.0884992946249 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07211E-04 | 0 |
| G/D | rs2092251339 |
None | None | N | 0.145 | 0.152 | 0.0884992946249 | gnomAD-4.0.0 | 1.2397E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.09789E-05 | 1.60061E-05 |
| G/R | None | None | 0.055 | N | 0.427 | 0.237 | 0.547384771329 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 6.33473E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.1039 | likely_benign | 0.0736 | benign | -0.466 | Destabilizing | None | N | 0.095 | neutral | N | 0.391999608 | None | None | I |
| G/C | 0.3725 | ambiguous | 0.253 | benign | -0.808 | Destabilizing | 0.612 | D | 0.504 | neutral | N | 0.503970995 | None | None | I |
| G/D | 0.397 | ambiguous | 0.2427 | benign | -0.707 | Destabilizing | None | N | 0.145 | neutral | N | 0.438923814 | None | None | I |
| G/E | 0.2501 | likely_benign | 0.1428 | benign | -0.82 | Destabilizing | None | N | 0.196 | neutral | None | None | None | None | I |
| G/F | 0.7416 | likely_pathogenic | 0.5972 | pathogenic | -0.938 | Destabilizing | 0.356 | N | 0.533 | neutral | None | None | None | None | I |
| G/H | 0.496 | ambiguous | 0.3212 | benign | -0.913 | Destabilizing | 0.214 | N | 0.492 | neutral | None | None | None | None | I |
| G/I | 0.3868 | ambiguous | 0.2368 | benign | -0.314 | Destabilizing | 0.214 | N | 0.511 | neutral | None | None | None | None | I |
| G/K | 0.5549 | ambiguous | 0.3503 | ambiguous | -1.057 | Destabilizing | 0.038 | N | 0.439 | neutral | None | None | None | None | I |
| G/L | 0.4292 | ambiguous | 0.2842 | benign | -0.314 | Destabilizing | 0.038 | N | 0.47 | neutral | None | None | None | None | I |
| G/M | 0.47 | ambiguous | 0.3266 | benign | -0.315 | Destabilizing | 0.676 | D | 0.501 | neutral | None | None | None | None | I |
| G/N | 0.3095 | likely_benign | 0.1985 | benign | -0.665 | Destabilizing | None | N | 0.139 | neutral | None | None | None | None | I |
| G/P | 0.7959 | likely_pathogenic | 0.6822 | pathogenic | -0.325 | Destabilizing | 0.214 | N | 0.456 | neutral | None | None | None | None | I |
| G/Q | 0.2927 | likely_benign | 0.1797 | benign | -0.899 | Destabilizing | 0.038 | N | 0.44 | neutral | None | None | None | None | I |
| G/R | 0.3995 | ambiguous | 0.2493 | benign | -0.665 | Destabilizing | 0.055 | N | 0.427 | neutral | N | 0.405543019 | None | None | I |
| G/S | 0.0958 | likely_benign | 0.0703 | benign | -0.882 | Destabilizing | 0.012 | N | 0.336 | neutral | N | 0.374927474 | None | None | I |
| G/T | 0.1539 | likely_benign | 0.093 | benign | -0.918 | Destabilizing | 0.038 | N | 0.445 | neutral | None | None | None | None | I |
| G/V | 0.2382 | likely_benign | 0.138 | benign | -0.325 | Destabilizing | 0.029 | N | 0.473 | neutral | N | 0.452462347 | None | None | I |
| G/W | 0.6411 | likely_pathogenic | 0.4697 | ambiguous | -1.204 | Destabilizing | 0.864 | D | 0.519 | neutral | None | None | None | None | I |
| G/Y | 0.6497 | likely_pathogenic | 0.4796 | ambiguous | -0.816 | Destabilizing | 0.356 | N | 0.533 | neutral | None | None | None | None | I |
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.