Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3026 | 9301;9302;9303 | chr2:178768760;178768759;178768758 | chr2:179633487;179633486;179633485 |
| N2AB | 3026 | 9301;9302;9303 | chr2:178768760;178768759;178768758 | chr2:179633487;179633486;179633485 |
| N2A | 3026 | 9301;9302;9303 | chr2:178768760;178768759;178768758 | chr2:179633487;179633486;179633485 |
| N2B | 2980 | 9163;9164;9165 | chr2:178768760;178768759;178768758 | chr2:179633487;179633486;179633485 |
| Novex-1 | 2980 | 9163;9164;9165 | chr2:178768760;178768759;178768758 | chr2:179633487;179633486;179633485 |
| Novex-2 | 2980 | 9163;9164;9165 | chr2:178768760;178768759;178768758 | chr2:179633487;179633486;179633485 |
| Novex-3 | 3026 | 9301;9302;9303 | chr2:178768760;178768759;178768758 | chr2:179633487;179633486;179633485 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/I | rs11900987  |
0.338 | 0.642 | N | 0.571 | 0.251 | None | gnomAD-2.1.1 | 5.87166E-04 | None | None | None | None | N | None | 6.36713E-03 | 5.65E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 3.1E-05 | 0 |
| N/I | rs11900987 |
0.338 | 0.642 | N | 0.571 | 0.251 | None | gnomAD-3.1.2 | 1.82638E-03 | None | None | None | None | N | None | 6.41737E-03 | 3.27097E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 2.39006E-03 |
| N/I | rs11900987 |
0.338 | 0.642 | N | 0.571 | 0.251 | None | 1000 genomes | 1.59744E-03 | None | None | None | None | N | None | 6.1E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| N/I | rs11900987 |
0.338 | 0.642 | N | 0.571 | 0.251 | None | gnomAD-4.0.0 | 4.50396E-04 | None | None | None | None | N | None | 7.95449E-03 | 1.83266E-04 | None | 0 | 0 | None | 0 | 9.89772E-04 | 2.37288E-05 | 5.48992E-05 | 1.27988E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.2335 | likely_benign | 0.4198 | ambiguous | -0.492 | Destabilizing | 0.176 | N | 0.468 | neutral | None | None | None | None | N |
| N/C | 0.2581 | likely_benign | 0.4428 | ambiguous | -0.478 | Destabilizing | 0.981 | D | 0.587 | neutral | None | None | None | None | N |
| N/D | 0.4326 | ambiguous | 0.5616 | ambiguous | -2.227 | Highly Destabilizing | 0.425 | N | 0.439 | neutral | N | 0.460287045 | None | None | N |
| N/E | 0.735 | likely_pathogenic | 0.8633 | pathogenic | -2.075 | Highly Destabilizing | 0.495 | N | 0.422 | neutral | None | None | None | None | N |
| N/F | 0.545 | ambiguous | 0.7442 | pathogenic | -0.52 | Destabilizing | 0.944 | D | 0.586 | neutral | None | None | None | None | N |
| N/G | 0.4134 | ambiguous | 0.6202 | pathogenic | -0.793 | Destabilizing | 0.329 | N | 0.391 | neutral | None | None | None | None | N |
| N/H | 0.1301 | likely_benign | 0.1858 | benign | -0.579 | Destabilizing | 0.975 | D | 0.515 | neutral | N | 0.442620588 | None | None | N |
| N/I | 0.171 | likely_benign | 0.2849 | benign | 0.263 | Stabilizing | 0.642 | D | 0.571 | neutral | N | 0.388828671 | None | None | N |
| N/K | 0.6575 | likely_pathogenic | 0.8311 | pathogenic | -0.103 | Destabilizing | 0.425 | N | 0.42 | neutral | N | 0.425863566 | None | None | N |
| N/L | 0.2347 | likely_benign | 0.3325 | benign | 0.263 | Stabilizing | 0.329 | N | 0.484 | neutral | None | None | None | None | N |
| N/M | 0.2647 | likely_benign | 0.4234 | ambiguous | 0.492 | Stabilizing | 0.981 | D | 0.57 | neutral | None | None | None | None | N |
| N/P | 0.9614 | likely_pathogenic | 0.973 | pathogenic | 0.039 | Stabilizing | 0.828 | D | 0.553 | neutral | None | None | None | None | N |
| N/Q | 0.4824 | ambiguous | 0.6725 | pathogenic | -1.1 | Destabilizing | 0.828 | D | 0.471 | neutral | None | None | None | None | N |
| N/R | 0.6722 | likely_pathogenic | 0.8192 | pathogenic | -0.055 | Destabilizing | 0.704 | D | 0.433 | neutral | None | None | None | None | N |
| N/S | 0.0785 | likely_benign | 0.1144 | benign | -0.921 | Destabilizing | 0.003 | N | 0.254 | neutral | N | 0.402233836 | None | None | N |
| N/T | 0.0872 | likely_benign | 0.1638 | benign | -0.618 | Destabilizing | 0.003 | N | 0.267 | neutral | N | 0.301555942 | None | None | N |
| N/V | 0.1791 | likely_benign | 0.3004 | benign | 0.039 | Stabilizing | 0.329 | N | 0.51 | neutral | None | None | None | None | N |
| N/W | 0.8554 | likely_pathogenic | 0.9291 | pathogenic | -0.533 | Destabilizing | 0.995 | D | 0.625 | neutral | None | None | None | None | N |
| N/Y | 0.213 | likely_benign | 0.336 | benign | -0.067 | Destabilizing | 0.975 | D | 0.569 | neutral | N | 0.473552143 | 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.