Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28419 | 85480;85481;85482 | chr2:178560877;178560876;178560875 | chr2:179425604;179425603;179425602 |
| N2AB | 26778 | 80557;80558;80559 | chr2:178560877;178560876;178560875 | chr2:179425604;179425603;179425602 |
| N2A | 25851 | 77776;77777;77778 | chr2:178560877;178560876;178560875 | chr2:179425604;179425603;179425602 |
| N2B | 19354 | 58285;58286;58287 | chr2:178560877;178560876;178560875 | chr2:179425604;179425603;179425602 |
| Novex-1 | 19479 | 58660;58661;58662 | chr2:178560877;178560876;178560875 | chr2:179425604;179425603;179425602 |
| Novex-2 | 19546 | 58861;58862;58863 | chr2:178560877;178560876;178560875 | chr2:179425604;179425603;179425602 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | None | None | 0.032 | N | 0.274 | 0.142 | 0.0846915920261 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/Y | rs1703397478  |
None | 0.997 | N | 0.677 | 0.396 | 0.51028768548 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3406 | ambiguous | 0.3098 | benign | -0.4 | Destabilizing | 0.698 | D | 0.513 | neutral | N | 0.469556861 | None | None | N |
| D/C | 0.8087 | likely_pathogenic | 0.7728 | pathogenic | -0.051 | Destabilizing | 0.998 | D | 0.713 | prob.delet. | None | None | None | None | N |
| D/E | 0.23 | likely_benign | 0.2304 | benign | -0.427 | Destabilizing | 0.014 | N | 0.233 | neutral | N | 0.484107151 | None | None | N |
| D/F | 0.7659 | likely_pathogenic | 0.7152 | pathogenic | -0.311 | Destabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | N |
| D/G | 0.214 | likely_benign | 0.1961 | benign | -0.64 | Destabilizing | 0.698 | D | 0.491 | neutral | N | 0.455465078 | None | None | N |
| D/H | 0.497 | ambiguous | 0.4256 | ambiguous | -0.381 | Destabilizing | 0.992 | D | 0.514 | neutral | N | 0.476900695 | None | None | N |
| D/I | 0.7177 | likely_pathogenic | 0.6785 | pathogenic | 0.195 | Stabilizing | 0.978 | D | 0.699 | prob.neutral | None | None | None | None | N |
| D/K | 0.6443 | likely_pathogenic | 0.5879 | pathogenic | -0.012 | Destabilizing | 0.754 | D | 0.495 | neutral | None | None | None | None | N |
| D/L | 0.6649 | likely_pathogenic | 0.6154 | pathogenic | 0.195 | Stabilizing | 0.956 | D | 0.688 | prob.neutral | None | None | None | None | N |
| D/M | 0.8458 | likely_pathogenic | 0.8034 | pathogenic | 0.462 | Stabilizing | 0.998 | D | 0.69 | prob.neutral | None | None | None | None | N |
| D/N | 0.1598 | likely_benign | 0.1404 | benign | -0.277 | Destabilizing | 0.032 | N | 0.274 | neutral | N | 0.465633247 | None | None | N |
| D/P | 0.9297 | likely_pathogenic | 0.9206 | pathogenic | 0.02 | Stabilizing | 0.978 | D | 0.517 | neutral | None | None | None | None | N |
| D/Q | 0.5655 | likely_pathogenic | 0.5215 | ambiguous | -0.224 | Destabilizing | 0.915 | D | 0.479 | neutral | None | None | None | None | N |
| D/R | 0.6659 | likely_pathogenic | 0.6054 | pathogenic | 0.143 | Stabilizing | 0.956 | D | 0.619 | neutral | None | None | None | None | N |
| D/S | 0.2468 | likely_benign | 0.2209 | benign | -0.432 | Destabilizing | 0.754 | D | 0.42 | neutral | None | None | None | None | N |
| D/T | 0.5188 | ambiguous | 0.4846 | ambiguous | -0.249 | Destabilizing | 0.956 | D | 0.497 | neutral | None | None | None | None | N |
| D/V | 0.4793 | ambiguous | 0.4484 | ambiguous | 0.02 | Stabilizing | 0.942 | D | 0.686 | prob.neutral | N | 0.477407675 | None | None | N |
| D/W | 0.9294 | likely_pathogenic | 0.9079 | pathogenic | -0.183 | Destabilizing | 0.998 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/Y | 0.2561 | likely_benign | 0.2236 | benign | -0.092 | Destabilizing | 0.997 | D | 0.677 | prob.neutral | N | 0.468760394 | 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.