Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27003 | 81232;81233;81234 | chr2:178565125;178565124;178565123 | chr2:179429852;179429851;179429850 |
| N2AB | 25362 | 76309;76310;76311 | chr2:178565125;178565124;178565123 | chr2:179429852;179429851;179429850 |
| N2A | 24435 | 73528;73529;73530 | chr2:178565125;178565124;178565123 | chr2:179429852;179429851;179429850 |
| N2B | 17938 | 54037;54038;54039 | chr2:178565125;178565124;178565123 | chr2:179429852;179429851;179429850 |
| Novex-1 | 18063 | 54412;54413;54414 | chr2:178565125;178565124;178565123 | chr2:179429852;179429851;179429850 |
| Novex-2 | 18130 | 54613;54614;54615 | chr2:178565125;178565124;178565123 | chr2:179429852;179429851;179429850 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/Y | rs1359547274  |
-1.298 | 0.99 | N | 0.666 | 0.513 | 0.739085393083 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 9.98E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| C/Y | rs1359547274 |
-1.298 | 0.99 | N | 0.666 | 0.513 | 0.739085393083 | gnomAD-4.0.0 | 1.59216E-06 | None | None | None | None | I | None | 0 | 0 | None | 4.7719E-05 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.7212 | likely_pathogenic | 0.6438 | pathogenic | -1.739 | Destabilizing | 0.559 | D | 0.563 | neutral | None | None | None | None | I |
| C/D | 0.9843 | likely_pathogenic | 0.9787 | pathogenic | -0.103 | Destabilizing | 0.956 | D | 0.697 | prob.neutral | None | None | None | None | I |
| C/E | 0.9925 | likely_pathogenic | 0.9902 | pathogenic | -0.044 | Destabilizing | 0.956 | D | 0.701 | prob.neutral | None | None | None | None | I |
| C/F | 0.7194 | likely_pathogenic | 0.6732 | pathogenic | -1.247 | Destabilizing | 0.97 | D | 0.663 | neutral | N | 0.477431944 | None | None | I |
| C/G | 0.5013 | ambiguous | 0.4401 | ambiguous | -2.003 | Highly Destabilizing | 0.698 | D | 0.656 | neutral | N | 0.462734588 | None | None | I |
| C/H | 0.9553 | likely_pathogenic | 0.9441 | pathogenic | -1.945 | Destabilizing | 0.998 | D | 0.698 | prob.neutral | None | None | None | None | I |
| C/I | 0.874 | likely_pathogenic | 0.8432 | pathogenic | -1.075 | Destabilizing | 0.978 | D | 0.605 | neutral | None | None | None | None | I |
| C/K | 0.9952 | likely_pathogenic | 0.9937 | pathogenic | -0.803 | Destabilizing | 0.956 | D | 0.693 | prob.neutral | None | None | None | None | I |
| C/L | 0.8778 | likely_pathogenic | 0.8481 | pathogenic | -1.075 | Destabilizing | 0.86 | D | 0.565 | neutral | None | None | None | None | I |
| C/M | 0.8839 | likely_pathogenic | 0.8531 | pathogenic | -0.237 | Destabilizing | 0.998 | D | 0.593 | neutral | None | None | None | None | I |
| C/N | 0.8721 | likely_pathogenic | 0.8401 | pathogenic | -0.614 | Destabilizing | 0.956 | D | 0.703 | prob.neutral | None | None | None | None | I |
| C/P | 0.9963 | likely_pathogenic | 0.9953 | pathogenic | -1.272 | Destabilizing | 0.978 | D | 0.697 | prob.neutral | None | None | None | None | I |
| C/Q | 0.9695 | likely_pathogenic | 0.9599 | pathogenic | -0.63 | Destabilizing | 0.956 | D | 0.708 | prob.delet. | None | None | None | None | I |
| C/R | 0.9673 | likely_pathogenic | 0.9602 | pathogenic | -0.561 | Destabilizing | 0.942 | D | 0.696 | prob.neutral | N | 0.516822576 | None | None | I |
| C/S | 0.4527 | ambiguous | 0.3874 | ambiguous | -1.199 | Destabilizing | 0.058 | N | 0.463 | neutral | N | 0.401574273 | None | None | I |
| C/T | 0.7328 | likely_pathogenic | 0.6978 | pathogenic | -0.969 | Destabilizing | 0.754 | D | 0.573 | neutral | None | None | None | None | I |
| C/V | 0.7392 | likely_pathogenic | 0.6922 | pathogenic | -1.272 | Destabilizing | 0.86 | D | 0.597 | neutral | None | None | None | None | I |
| C/W | 0.9432 | likely_pathogenic | 0.9273 | pathogenic | -1.143 | Destabilizing | 0.997 | D | 0.689 | prob.neutral | N | 0.50392999 | None | None | I |
| C/Y | 0.8936 | likely_pathogenic | 0.8635 | pathogenic | -1.155 | Destabilizing | 0.99 | D | 0.666 | neutral | N | 0.485572246 | None | None | I |
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.