Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3346 | 10261;10262;10263 | chr2:178764255;178764254;178764253 | chr2:179628982;179628981;179628980 |
| N2AB | 3346 | 10261;10262;10263 | chr2:178764255;178764254;178764253 | chr2:179628982;179628981;179628980 |
| N2A | 3346 | 10261;10262;10263 | chr2:178764255;178764254;178764253 | chr2:179628982;179628981;179628980 |
| N2B | 3300 | 10123;10124;10125 | chr2:178764255;178764254;178764253 | chr2:179628982;179628981;179628980 |
| Novex-1 | 3300 | 10123;10124;10125 | chr2:178764255;178764254;178764253 | chr2:179628982;179628981;179628980 |
| Novex-2 | 3300 | 10123;10124;10125 | chr2:178764255;178764254;178764253 | chr2:179628982;179628981;179628980 |
| Novex-3 | 3346 | 10261;10262;10263 | chr2:178764255;178764254;178764253 | chr2:179628982;179628981;179628980 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | None | None | 0.484 | N | 0.351 | 0.279 | 0.3691244813 | gnomAD-4.0.0 | 1.36819E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.04337E-05 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | None | None | None | N | 0.239 | 0.063 | 0.256283259241 | gnomAD-4.0.0 | 6.84097E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99315E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5227 | ambiguous | 0.5095 | ambiguous | -0.868 | Destabilizing | 0.824 | D | 0.347 | neutral | None | None | None | None | N |
| A/D | 0.2415 | likely_benign | 0.2879 | benign | -0.36 | Destabilizing | 0.062 | N | 0.361 | neutral | N | 0.488979689 | None | None | N |
| A/E | 0.1634 | likely_benign | 0.2 | benign | -0.438 | Destabilizing | 0.001 | N | 0.207 | neutral | None | None | None | None | N |
| A/F | 0.2964 | likely_benign | 0.3559 | ambiguous | -0.624 | Destabilizing | 0.555 | D | 0.391 | neutral | None | None | None | None | N |
| A/G | 0.1844 | likely_benign | 0.197 | benign | -0.518 | Destabilizing | 0.062 | N | 0.317 | neutral | N | 0.510642928 | None | None | N |
| A/H | 0.3783 | ambiguous | 0.4385 | ambiguous | -0.417 | Destabilizing | 0.824 | D | 0.378 | neutral | None | None | None | None | N |
| A/I | 0.1809 | likely_benign | 0.2129 | benign | -0.147 | Destabilizing | 0.081 | N | 0.304 | neutral | None | None | None | None | N |
| A/K | 0.2925 | likely_benign | 0.3621 | ambiguous | -0.794 | Destabilizing | 0.081 | N | 0.313 | neutral | None | None | None | None | N |
| A/L | 0.1523 | likely_benign | 0.1874 | benign | -0.147 | Destabilizing | 0.035 | N | 0.335 | neutral | None | None | None | None | N |
| A/M | 0.1652 | likely_benign | 0.1927 | benign | -0.429 | Destabilizing | 0.555 | D | 0.325 | neutral | None | None | None | None | N |
| A/N | 0.1803 | likely_benign | 0.2324 | benign | -0.631 | Destabilizing | 0.235 | N | 0.38 | neutral | None | None | None | None | N |
| A/P | 0.7645 | likely_pathogenic | 0.865 | pathogenic | -0.183 | Destabilizing | 0.484 | N | 0.351 | neutral | N | 0.483302025 | None | None | N |
| A/Q | 0.2194 | likely_benign | 0.2586 | benign | -0.778 | Destabilizing | 0.235 | N | 0.344 | neutral | None | None | None | None | N |
| A/R | 0.245 | likely_benign | 0.2952 | benign | -0.411 | Destabilizing | 0.38 | N | 0.341 | neutral | None | None | None | None | N |
| A/S | 0.081 | likely_benign | 0.0896 | benign | -0.92 | Destabilizing | None | N | 0.214 | neutral | N | 0.445563128 | None | None | N |
| A/T | 0.0625 | likely_benign | 0.0724 | benign | -0.896 | Destabilizing | None | N | 0.239 | neutral | N | 0.4284827 | None | None | N |
| A/V | 0.0972 | likely_benign | 0.1046 | benign | -0.183 | Destabilizing | 0.001 | N | 0.102 | neutral | N | 0.380792682 | None | None | N |
| A/W | 0.7468 | likely_pathogenic | 0.7872 | pathogenic | -0.861 | Destabilizing | 0.935 | D | 0.569 | neutral | None | None | None | None | N |
| A/Y | 0.4311 | ambiguous | 0.482 | ambiguous | -0.477 | Destabilizing | 0.555 | D | 0.391 | 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.