Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18132 | 54619;54620;54621 | chr2:178604293;178604292;178604291 | chr2:179469020;179469019;179469018 |
| N2AB | 16491 | 49696;49697;49698 | chr2:178604293;178604292;178604291 | chr2:179469020;179469019;179469018 |
| N2A | 15564 | 46915;46916;46917 | chr2:178604293;178604292;178604291 | chr2:179469020;179469019;179469018 |
| N2B | 9067 | 27424;27425;27426 | chr2:178604293;178604292;178604291 | chr2:179469020;179469019;179469018 |
| Novex-1 | 9192 | 27799;27800;27801 | chr2:178604293;178604292;178604291 | chr2:179469020;179469019;179469018 |
| Novex-2 | 9259 | 28000;28001;28002 | chr2:178604293;178604292;178604291 | chr2:179469020;179469019;179469018 |
| 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/N | rs769730131  |
-0.535 | 0.642 | N | 0.385 | 0.183 | 0.644471222209 | gnomAD-2.1.1 | 6.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 7.42E-05 | None | 0 | None | 0 | 0 | 0 |
| I/N | rs769730131 |
-0.535 | 0.642 | N | 0.385 | 0.183 | 0.644471222209 | gnomAD-4.0.0 | 2.09592E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.00625E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | None | None | 0.01 | N | 0.107 | 0.149 | 0.53600533864 | gnomAD-4.0.0 | 4.19184E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.00625E-05 | None | 0 | 0 | 3.64631E-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 | 0.2981 | likely_benign | 0.4911 | ambiguous | -1.226 | Destabilizing | 0.003 | N | 0.12 | neutral | None | None | None | None | N |
| I/C | 0.7146 | likely_pathogenic | 0.8129 | pathogenic | -0.87 | Destabilizing | 0.981 | D | 0.318 | neutral | None | None | None | None | N |
| I/D | 0.5713 | likely_pathogenic | 0.7372 | pathogenic | -0.427 | Destabilizing | 0.003 | N | 0.142 | neutral | None | None | None | None | N |
| I/E | 0.4434 | ambiguous | 0.6048 | pathogenic | -0.415 | Destabilizing | 0.004 | N | 0.138 | neutral | None | None | None | None | N |
| I/F | 0.1747 | likely_benign | 0.2229 | benign | -0.728 | Destabilizing | 0.784 | D | 0.203 | neutral | N | 0.49373786 | None | None | N |
| I/G | 0.5808 | likely_pathogenic | 0.781 | pathogenic | -1.524 | Destabilizing | 0.329 | N | 0.299 | neutral | None | None | None | None | N |
| I/H | 0.3938 | ambiguous | 0.4956 | ambiguous | -0.54 | Destabilizing | 0.981 | D | 0.391 | neutral | None | None | None | None | N |
| I/K | 0.3065 | likely_benign | 0.4192 | ambiguous | -0.749 | Destabilizing | 0.495 | N | 0.314 | neutral | None | None | None | None | N |
| I/L | 0.0872 | likely_benign | 0.1104 | benign | -0.497 | Destabilizing | 0.139 | N | 0.173 | neutral | N | 0.449888295 | None | None | N |
| I/M | 0.1108 | likely_benign | 0.1417 | benign | -0.567 | Destabilizing | 0.927 | D | 0.206 | neutral | N | 0.49373786 | None | None | N |
| I/N | 0.2027 | likely_benign | 0.3102 | benign | -0.695 | Destabilizing | 0.642 | D | 0.385 | neutral | N | 0.44098081 | None | None | N |
| I/P | 0.5702 | likely_pathogenic | 0.7291 | pathogenic | -0.708 | Destabilizing | 0.828 | D | 0.419 | neutral | None | None | None | None | N |
| I/Q | 0.2764 | likely_benign | 0.3969 | ambiguous | -0.807 | Destabilizing | 0.704 | D | 0.423 | neutral | None | None | None | None | N |
| I/R | 0.2912 | likely_benign | 0.3812 | ambiguous | -0.209 | Destabilizing | 0.704 | D | 0.428 | neutral | None | None | None | None | N |
| I/S | 0.2286 | likely_benign | 0.3634 | ambiguous | -1.311 | Destabilizing | 0.27 | N | 0.287 | neutral | N | 0.444405118 | None | None | N |
| I/T | 0.2319 | likely_benign | 0.3882 | ambiguous | -1.173 | Destabilizing | 0.01 | N | 0.107 | neutral | N | 0.441922173 | None | None | N |
| I/V | 0.1065 | likely_benign | 0.1592 | benign | -0.708 | Destabilizing | 0.003 | N | 0.094 | neutral | N | 0.435958993 | None | None | N |
| I/W | 0.7416 | likely_pathogenic | 0.7927 | pathogenic | -0.772 | Destabilizing | 0.995 | D | 0.395 | neutral | None | None | None | None | N |
| I/Y | 0.4385 | ambiguous | 0.5123 | ambiguous | -0.541 | Destabilizing | 0.981 | D | 0.377 | 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.