Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16661 | 50206;50207;50208 | chr2:178612544;178612543;178612542 | chr2:179477271;179477270;179477269 |
| N2AB | 15020 | 45283;45284;45285 | chr2:178612544;178612543;178612542 | chr2:179477271;179477270;179477269 |
| N2A | 14093 | 42502;42503;42504 | chr2:178612544;178612543;178612542 | chr2:179477271;179477270;179477269 |
| N2B | 7596 | 23011;23012;23013 | chr2:178612544;178612543;178612542 | chr2:179477271;179477270;179477269 |
| Novex-1 | 7721 | 23386;23387;23388 | chr2:178612544;178612543;178612542 | chr2:179477271;179477270;179477269 |
| Novex-2 | 7788 | 23587;23588;23589 | chr2:178612544;178612543;178612542 | chr2:179477271;179477270;179477269 |
| 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 | None | None | 0.961 | N | 0.467 | 0.311 | 0.586144602217 | gnomAD-4.0.0 | 1.3702E-06 | None | None | None | None | N | None | 0 | 0 | None | 3.83083E-05 | 0 | None | 0 | 0 | 0 | 0 | 1.65942E-05 |
| I/V | rs1353241870  |
-0.255 | 0.044 | N | 0.107 | 0.103 | 0.523961927912 | gnomAD-2.1.1 | 4.12E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 0 | 0 |
| I/V | rs1353241870 |
-0.255 | 0.044 | N | 0.107 | 0.103 | 0.523961927912 | gnomAD-4.0.0 | 1.59611E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43521E-05 | 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 | 0.5138 | ambiguous | 0.5491 | ambiguous | -0.984 | Destabilizing | 0.931 | D | 0.464 | neutral | None | None | None | None | N |
| I/C | 0.7863 | likely_pathogenic | 0.8216 | pathogenic | -0.638 | Destabilizing | 1.0 | D | 0.559 | neutral | None | None | None | None | N |
| I/D | 0.8505 | likely_pathogenic | 0.9175 | pathogenic | -0.492 | Destabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | N |
| I/E | 0.6698 | likely_pathogenic | 0.7923 | pathogenic | -0.572 | Destabilizing | 0.999 | D | 0.591 | neutral | None | None | None | None | N |
| I/F | 0.3532 | ambiguous | 0.384 | ambiguous | -0.852 | Destabilizing | 0.994 | D | 0.494 | neutral | N | 0.483118021 | None | None | N |
| I/G | 0.774 | likely_pathogenic | 0.8219 | pathogenic | -1.194 | Destabilizing | 0.999 | D | 0.541 | neutral | None | None | None | None | N |
| I/H | 0.7287 | likely_pathogenic | 0.7975 | pathogenic | -0.406 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| I/K | 0.5986 | likely_pathogenic | 0.7572 | pathogenic | -0.603 | Destabilizing | 0.999 | D | 0.605 | neutral | None | None | None | None | N |
| I/L | 0.1909 | likely_benign | 0.1905 | benign | -0.536 | Destabilizing | 0.689 | D | 0.174 | neutral | N | 0.446762896 | None | None | N |
| I/M | 0.1533 | likely_benign | 0.1679 | benign | -0.421 | Destabilizing | 0.994 | D | 0.55 | neutral | N | 0.479486329 | None | None | N |
| I/N | 0.4086 | ambiguous | 0.4873 | ambiguous | -0.344 | Destabilizing | 0.998 | D | 0.638 | neutral | N | 0.475145118 | None | None | N |
| I/P | 0.9644 | likely_pathogenic | 0.9731 | pathogenic | -0.652 | Destabilizing | 0.999 | D | 0.637 | neutral | None | None | None | None | N |
| I/Q | 0.5762 | likely_pathogenic | 0.6639 | pathogenic | -0.604 | Destabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | N |
| I/R | 0.5622 | ambiguous | 0.7177 | pathogenic | 0.041 | Stabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | N |
| I/S | 0.4097 | ambiguous | 0.4602 | ambiguous | -0.837 | Destabilizing | 0.994 | D | 0.502 | neutral | N | 0.365399367 | None | None | N |
| I/T | 0.2618 | likely_benign | 0.3099 | benign | -0.81 | Destabilizing | 0.961 | D | 0.467 | neutral | N | 0.384337754 | None | None | N |
| I/V | 0.1028 | likely_benign | 0.1028 | benign | -0.652 | Destabilizing | 0.044 | N | 0.107 | neutral | N | 0.372218716 | None | None | N |
| I/W | 0.8792 | likely_pathogenic | 0.9236 | pathogenic | -0.851 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| I/Y | 0.7401 | likely_pathogenic | 0.8028 | pathogenic | -0.626 | Destabilizing | 0.999 | D | 0.579 | 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.