Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21476 | 64651;64652;64653 | chr2:178585318;178585317;178585316 | chr2:179450045;179450044;179450043 |
| N2AB | 19835 | 59728;59729;59730 | chr2:178585318;178585317;178585316 | chr2:179450045;179450044;179450043 |
| N2A | 18908 | 56947;56948;56949 | chr2:178585318;178585317;178585316 | chr2:179450045;179450044;179450043 |
| N2B | 12411 | 37456;37457;37458 | chr2:178585318;178585317;178585316 | chr2:179450045;179450044;179450043 |
| Novex-1 | 12536 | 37831;37832;37833 | chr2:178585318;178585317;178585316 | chr2:179450045;179450044;179450043 |
| Novex-2 | 12603 | 38032;38033;38034 | chr2:178585318;178585317;178585316 | chr2:179450045;179450044;179450043 |
| 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/L | rs898981554  |
-0.372 | 0.084 | N | 0.249 | 0.064 | 0.267755039894 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9E-06 | 0 |
| I/L | rs898981554 |
-0.372 | 0.084 | N | 0.249 | 0.064 | 0.267755039894 | gnomAD-4.0.0 | 2.05911E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.70343E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.497 | ambiguous | 0.4107 | ambiguous | -2.144 | Highly Destabilizing | 0.218 | N | 0.403 | neutral | None | None | None | None | N |
| I/C | 0.6376 | likely_pathogenic | 0.6059 | pathogenic | -1.491 | Destabilizing | 0.973 | D | 0.452 | neutral | None | None | None | None | N |
| I/D | 0.8834 | likely_pathogenic | 0.7773 | pathogenic | -1.953 | Destabilizing | 0.906 | D | 0.571 | neutral | None | None | None | None | N |
| I/E | 0.7457 | likely_pathogenic | 0.6053 | pathogenic | -1.803 | Destabilizing | 0.906 | D | 0.546 | neutral | None | None | None | None | N |
| I/F | 0.1828 | likely_benign | 0.1546 | benign | -1.214 | Destabilizing | 0.826 | D | 0.392 | neutral | None | None | None | None | N |
| I/G | 0.8194 | likely_pathogenic | 0.7398 | pathogenic | -2.621 | Highly Destabilizing | 0.906 | D | 0.512 | neutral | None | None | None | None | N |
| I/H | 0.6143 | likely_pathogenic | 0.5157 | ambiguous | -1.869 | Destabilizing | 0.991 | D | 0.595 | neutral | None | None | None | None | N |
| I/K | 0.5833 | likely_pathogenic | 0.4461 | ambiguous | -1.758 | Destabilizing | 0.879 | D | 0.547 | neutral | N | 0.494406197 | None | None | N |
| I/L | 0.1147 | likely_benign | 0.0972 | benign | -0.818 | Destabilizing | 0.084 | N | 0.249 | neutral | N | 0.479262345 | None | None | N |
| I/M | 0.0926 | likely_benign | 0.0772 | benign | -0.732 | Destabilizing | 0.782 | D | 0.44 | neutral | N | 0.521207755 | None | None | N |
| I/N | 0.4845 | ambiguous | 0.3576 | ambiguous | -1.878 | Destabilizing | 0.967 | D | 0.578 | neutral | None | None | None | None | N |
| I/P | 0.9649 | likely_pathogenic | 0.9361 | pathogenic | -1.234 | Destabilizing | 0.967 | D | 0.573 | neutral | None | None | None | None | N |
| I/Q | 0.586 | likely_pathogenic | 0.463 | ambiguous | -1.844 | Destabilizing | 0.967 | D | 0.588 | neutral | None | None | None | None | N |
| I/R | 0.5428 | ambiguous | 0.4056 | ambiguous | -1.326 | Destabilizing | 0.879 | D | 0.583 | neutral | N | 0.490140236 | None | None | N |
| I/S | 0.5513 | ambiguous | 0.4447 | ambiguous | -2.577 | Highly Destabilizing | 0.826 | D | 0.469 | neutral | None | None | None | None | N |
| I/T | 0.406 | ambiguous | 0.3333 | benign | -2.286 | Highly Destabilizing | 0.505 | D | 0.385 | neutral | N | 0.509990683 | None | None | N |
| I/V | 0.0816 | likely_benign | 0.0779 | benign | -1.234 | Destabilizing | None | N | 0.119 | neutral | N | 0.401529493 | None | None | N |
| I/W | 0.78 | likely_pathogenic | 0.7261 | pathogenic | -1.467 | Destabilizing | 0.991 | D | 0.665 | neutral | None | None | None | None | N |
| I/Y | 0.4741 | ambiguous | 0.4072 | ambiguous | -1.201 | Destabilizing | 0.906 | D | 0.462 | 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.