Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28421 | 85486;85487;85488 | chr2:178560871;178560870;178560869 | chr2:179425598;179425597;179425596 |
| N2AB | 26780 | 80563;80564;80565 | chr2:178560871;178560870;178560869 | chr2:179425598;179425597;179425596 |
| N2A | 25853 | 77782;77783;77784 | chr2:178560871;178560870;178560869 | chr2:179425598;179425597;179425596 |
| N2B | 19356 | 58291;58292;58293 | chr2:178560871;178560870;178560869 | chr2:179425598;179425597;179425596 |
| Novex-1 | 19481 | 58666;58667;58668 | chr2:178560871;178560870;178560869 | chr2:179425598;179425597;179425596 |
| Novex-2 | 19548 | 58867;58868;58869 | chr2:178560871;178560870;178560869 | chr2:179425598;179425597;179425596 |
| 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/K | rs749273378  |
-0.492 | 0.667 | N | 0.634 | 0.308 | 0.776285685458 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/K | rs749273378 |
-0.492 | 0.667 | N | 0.634 | 0.308 | 0.776285685458 | gnomAD-4.0.0 | 1.59154E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43283E-05 | 0 |
| I/T | rs749273378 |
None | 0.124 | N | 0.448 | 0.261 | 0.578844998551 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs749273378 |
None | 0.124 | N | 0.448 | 0.261 | 0.578844998551 | gnomAD-4.0.0 | 2.56253E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39284E-06 | 0 | 2.84544E-05 |
| I/V | rs371356428 |
-0.604 | None | N | 0.187 | 0.038 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs371356428 |
-0.604 | None | N | 0.187 | 0.038 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs371356428 |
-0.604 | None | N | 0.187 | 0.038 | None | gnomAD-4.0.0 | 3.71833E-06 | None | None | None | None | N | None | 1.33447E-05 | 0 | None | 0 | 4.46528E-05 | None | 3.1249E-05 | 0 | 8.4759E-07 | 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 | 0.2096 | likely_benign | 0.1962 | benign | -1.298 | Destabilizing | 0.072 | N | 0.44 | neutral | None | None | None | None | N |
| I/C | 0.4818 | ambiguous | 0.4493 | ambiguous | -0.655 | Destabilizing | 0.909 | D | 0.489 | neutral | None | None | None | None | N |
| I/D | 0.377 | ambiguous | 0.3535 | ambiguous | -0.87 | Destabilizing | 0.726 | D | 0.643 | neutral | None | None | None | None | N |
| I/E | 0.3019 | likely_benign | 0.2884 | benign | -0.946 | Destabilizing | 0.726 | D | 0.639 | neutral | None | None | None | None | N |
| I/F | 0.1405 | likely_benign | 0.127 | benign | -1.199 | Destabilizing | 0.567 | D | 0.431 | neutral | None | None | None | None | N |
| I/G | 0.3592 | ambiguous | 0.3192 | benign | -1.534 | Destabilizing | 0.726 | D | 0.633 | neutral | None | None | None | None | N |
| I/H | 0.2926 | likely_benign | 0.2787 | benign | -0.808 | Destabilizing | 0.968 | D | 0.663 | neutral | None | None | None | None | N |
| I/K | 0.191 | likely_benign | 0.1781 | benign | -0.757 | Destabilizing | 0.667 | D | 0.634 | neutral | N | 0.43875973 | None | None | N |
| I/L | 0.0836 | likely_benign | 0.08 | benign | -0.76 | Destabilizing | None | N | 0.195 | neutral | N | 0.495231875 | None | None | N |
| I/M | 0.0964 | likely_benign | 0.089 | benign | -0.427 | Destabilizing | 0.497 | N | 0.437 | neutral | N | 0.508334458 | None | None | N |
| I/N | 0.1223 | likely_benign | 0.1219 | benign | -0.431 | Destabilizing | 0.89 | D | 0.646 | neutral | None | None | None | None | N |
| I/P | 0.7632 | likely_pathogenic | 0.6998 | pathogenic | -0.907 | Destabilizing | 0.726 | D | 0.641 | neutral | None | None | None | None | N |
| I/Q | 0.2189 | likely_benign | 0.2052 | benign | -0.728 | Destabilizing | 0.89 | D | 0.641 | neutral | None | None | None | None | N |
| I/R | 0.1479 | likely_benign | 0.1414 | benign | -0.09 | Destabilizing | 0.667 | D | 0.647 | neutral | N | 0.452171744 | None | None | N |
| I/S | 0.1231 | likely_benign | 0.1205 | benign | -0.942 | Destabilizing | 0.567 | D | 0.513 | neutral | None | None | None | None | N |
| I/T | 0.1268 | likely_benign | 0.1243 | benign | -0.913 | Destabilizing | 0.124 | N | 0.448 | neutral | N | 0.431719114 | None | None | N |
| I/V | 0.0628 | likely_benign | 0.0613 | benign | -0.907 | Destabilizing | None | N | 0.187 | neutral | N | 0.459945865 | None | None | N |
| I/W | 0.7153 | likely_pathogenic | 0.6819 | pathogenic | -1.202 | Destabilizing | 0.968 | D | 0.709 | prob.delet. | None | None | None | None | N |
| I/Y | 0.3729 | ambiguous | 0.3636 | ambiguous | -0.975 | Destabilizing | 0.726 | D | 0.457 | 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.