Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2595 | 8008;8009;8010 | chr2:178773181;178773180;178773179 | chr2:179637908;179637907;179637906 |
| N2AB | 2595 | 8008;8009;8010 | chr2:178773181;178773180;178773179 | chr2:179637908;179637907;179637906 |
| N2A | 2595 | 8008;8009;8010 | chr2:178773181;178773180;178773179 | chr2:179637908;179637907;179637906 |
| N2B | 2549 | 7870;7871;7872 | chr2:178773181;178773180;178773179 | chr2:179637908;179637907;179637906 |
| Novex-1 | 2549 | 7870;7871;7872 | chr2:178773181;178773180;178773179 | chr2:179637908;179637907;179637906 |
| Novex-2 | 2549 | 7870;7871;7872 | chr2:178773181;178773180;178773179 | chr2:179637908;179637907;179637906 |
| Novex-3 | 2595 | 8008;8009;8010 | chr2:178773181;178773180;178773179 | chr2:179637908;179637907;179637906 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/V | rs760786665  |
-0.903 | 0.985 | N | 0.451 | 0.383 | 0.682569885038 | gnomAD-2.1.1 | 2.4E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.3E-05 | 0 |
| M/V | rs760786665 |
-0.903 | 0.985 | N | 0.451 | 0.383 | 0.682569885038 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| M/V | rs760786665 |
-0.903 | 0.985 | N | 0.451 | 0.383 | 0.682569885038 | gnomAD-4.0.0 | 3.20247E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.7411E-05 | 0 | 2.84333E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.645 | likely_pathogenic | 0.658 | pathogenic | -1.154 | Destabilizing | 0.989 | D | 0.511 | neutral | None | None | None | None | N |
| M/C | 0.8513 | likely_pathogenic | 0.8787 | pathogenic | -0.429 | Destabilizing | 1.0 | D | 0.558 | neutral | None | None | None | None | N |
| M/D | 0.828 | likely_pathogenic | 0.8197 | pathogenic | -0.416 | Destabilizing | 0.999 | D | 0.672 | neutral | None | None | None | None | N |
| M/E | 0.5118 | ambiguous | 0.5082 | ambiguous | -0.472 | Destabilizing | 0.999 | D | 0.527 | neutral | None | None | None | None | N |
| M/F | 0.5268 | ambiguous | 0.5685 | pathogenic | -0.803 | Destabilizing | 0.999 | D | 0.46 | neutral | None | None | None | None | N |
| M/G | 0.6437 | likely_pathogenic | 0.632 | pathogenic | -1.35 | Destabilizing | 0.995 | D | 0.561 | neutral | None | None | None | None | N |
| M/H | 0.6431 | likely_pathogenic | 0.6297 | pathogenic | -0.556 | Destabilizing | 1.0 | D | 0.644 | neutral | None | None | None | None | N |
| M/I | 0.7696 | likely_pathogenic | 0.7973 | pathogenic | -0.701 | Destabilizing | 0.985 | D | 0.498 | neutral | N | 0.509097814 | None | None | N |
| M/K | 0.2247 | likely_benign | 0.2178 | benign | -0.056 | Destabilizing | 0.994 | D | 0.521 | neutral | N | 0.487446492 | None | None | N |
| M/L | 0.2012 | likely_benign | 0.2128 | benign | -0.701 | Destabilizing | 0.927 | D | 0.299 | neutral | N | 0.508602122 | None | None | N |
| M/N | 0.5505 | ambiguous | 0.5373 | ambiguous | 0.223 | Stabilizing | 0.999 | D | 0.64 | neutral | None | None | None | None | N |
| M/P | 0.9322 | likely_pathogenic | 0.9277 | pathogenic | -0.826 | Destabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | N |
| M/Q | 0.2171 | likely_benign | 0.2105 | benign | -0.014 | Destabilizing | 0.999 | D | 0.467 | neutral | None | None | None | None | N |
| M/R | 0.2398 | likely_benign | 0.2392 | benign | 0.513 | Stabilizing | 0.998 | D | 0.503 | neutral | N | 0.492885905 | None | None | N |
| M/S | 0.558 | ambiguous | 0.5493 | ambiguous | -0.221 | Destabilizing | 0.995 | D | 0.49 | neutral | None | None | None | None | N |
| M/T | 0.4014 | ambiguous | 0.3979 | ambiguous | -0.187 | Destabilizing | 0.994 | D | 0.516 | neutral | N | 0.44297243 | None | None | N |
| M/V | 0.2686 | likely_benign | 0.2937 | benign | -0.826 | Destabilizing | 0.985 | D | 0.451 | neutral | N | 0.4920411 | None | None | N |
| M/W | 0.7795 | likely_pathogenic | 0.7989 | pathogenic | -0.707 | Destabilizing | 1.0 | D | 0.595 | neutral | None | None | None | None | N |
| M/Y | 0.7407 | likely_pathogenic | 0.759 | pathogenic | -0.638 | Destabilizing | 0.999 | D | 0.549 | 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.