Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25042 | 75349;75350;75351 | chr2:178571008;178571007;178571006 | chr2:179435735;179435734;179435733 |
| N2AB | 23401 | 70426;70427;70428 | chr2:178571008;178571007;178571006 | chr2:179435735;179435734;179435733 |
| N2A | 22474 | 67645;67646;67647 | chr2:178571008;178571007;178571006 | chr2:179435735;179435734;179435733 |
| N2B | 15977 | 48154;48155;48156 | chr2:178571008;178571007;178571006 | chr2:179435735;179435734;179435733 |
| Novex-1 | 16102 | 48529;48530;48531 | chr2:178571008;178571007;178571006 | chr2:179435735;179435734;179435733 |
| Novex-2 | 16169 | 48730;48731;48732 | chr2:178571008;178571007;178571006 | chr2:179435735;179435734;179435733 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs775091036  |
-2.622 | None | N | 0.418 | 0.1 | None | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/T | rs775091036 |
-2.622 | None | N | 0.418 | 0.1 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| I/T | rs775091036 |
-2.622 | None | N | 0.418 | 0.1 | None | gnomAD-4.0.0 | 5.58005E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.64636E-04 | 6.78423E-06 | 0 | 0 |
| I/V | None | None | None | N | 0.173 | 0.066 | 0.188950314367 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3116 | likely_benign | 0.2816 | benign | -2.326 | Highly Destabilizing | 0.007 | N | 0.595 | neutral | None | None | None | None | N |
| I/C | 0.6413 | likely_pathogenic | 0.6475 | pathogenic | -1.632 | Destabilizing | 0.356 | N | 0.658 | neutral | None | None | None | None | N |
| I/D | 0.813 | likely_pathogenic | 0.7881 | pathogenic | -2.443 | Highly Destabilizing | 0.136 | N | 0.706 | prob.neutral | None | None | None | None | N |
| I/E | 0.7217 | likely_pathogenic | 0.705 | pathogenic | -2.229 | Highly Destabilizing | 0.136 | N | 0.683 | prob.neutral | None | None | None | None | N |
| I/F | 0.1675 | likely_benign | 0.1842 | benign | -1.331 | Destabilizing | None | N | 0.292 | neutral | N | 0.519249593 | None | None | N |
| I/G | 0.7541 | likely_pathogenic | 0.7246 | pathogenic | -2.861 | Highly Destabilizing | 0.136 | N | 0.682 | prob.neutral | None | None | None | None | N |
| I/H | 0.5327 | ambiguous | 0.5337 | ambiguous | -2.306 | Highly Destabilizing | 0.628 | D | 0.677 | prob.neutral | None | None | None | None | N |
| I/K | 0.62 | likely_pathogenic | 0.6114 | pathogenic | -1.739 | Destabilizing | 0.136 | N | 0.688 | prob.neutral | None | None | None | None | N |
| I/L | 0.1104 | likely_benign | 0.116 | benign | -0.796 | Destabilizing | 0.002 | N | 0.401 | neutral | N | 0.484982304 | None | None | N |
| I/M | 0.0906 | likely_benign | 0.0923 | benign | -0.801 | Destabilizing | 0.171 | N | 0.624 | neutral | N | 0.484041763 | None | None | N |
| I/N | 0.3501 | ambiguous | 0.3139 | benign | -2.025 | Highly Destabilizing | 0.295 | N | 0.709 | prob.delet. | N | 0.470150562 | None | None | N |
| I/P | 0.98 | likely_pathogenic | 0.9747 | pathogenic | -1.285 | Destabilizing | 0.628 | D | 0.711 | prob.delet. | None | None | None | None | N |
| I/Q | 0.5569 | ambiguous | 0.547 | ambiguous | -1.9 | Destabilizing | 0.628 | D | 0.694 | prob.neutral | None | None | None | None | N |
| I/R | 0.5041 | ambiguous | 0.4894 | ambiguous | -1.472 | Destabilizing | 0.356 | N | 0.699 | prob.neutral | None | None | None | None | N |
| I/S | 0.2844 | likely_benign | 0.2438 | benign | -2.737 | Highly Destabilizing | 0.029 | N | 0.663 | neutral | N | 0.468060194 | None | None | N |
| I/T | 0.1253 | likely_benign | 0.1048 | benign | -2.378 | Highly Destabilizing | None | N | 0.418 | neutral | N | 0.495140582 | None | None | N |
| I/V | 0.0581 | likely_benign | 0.0576 | benign | -1.285 | Destabilizing | None | N | 0.173 | neutral | N | 0.440615451 | None | None | N |
| I/W | 0.751 | likely_pathogenic | 0.7616 | pathogenic | -1.702 | Destabilizing | 0.864 | D | 0.683 | prob.neutral | None | None | None | None | N |
| I/Y | 0.5122 | ambiguous | 0.5246 | ambiguous | -1.393 | Destabilizing | 0.038 | N | 0.683 | prob.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.