Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30212 | 90859;90860;90861 | chr2:178552266;178552265;178552264 | chr2:179416993;179416992;179416991 |
| N2AB | 28571 | 85936;85937;85938 | chr2:178552266;178552265;178552264 | chr2:179416993;179416992;179416991 |
| N2A | 27644 | 83155;83156;83157 | chr2:178552266;178552265;178552264 | chr2:179416993;179416992;179416991 |
| N2B | 21147 | 63664;63665;63666 | chr2:178552266;178552265;178552264 | chr2:179416993;179416992;179416991 |
| Novex-1 | 21272 | 64039;64040;64041 | chr2:178552266;178552265;178552264 | chr2:179416993;179416992;179416991 |
| Novex-2 | 21339 | 64240;64241;64242 | chr2:178552266;178552265;178552264 | chr2:179416993;179416992;179416991 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/T | rs762512777  |
-0.261 | 0.98 | N | 0.463 | 0.302 | 0.328222422547 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| R/T | rs762512777 |
-0.261 | 0.98 | N | 0.463 | 0.302 | 0.328222422547 | gnomAD-4.0.0 | 7.20193E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.87501E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7789 | likely_pathogenic | 0.6437 | pathogenic | -0.15 | Destabilizing | 0.931 | D | 0.443 | neutral | None | None | None | None | I |
| R/C | 0.374 | ambiguous | 0.296 | benign | -0.171 | Destabilizing | 1.0 | D | 0.555 | neutral | None | None | None | None | I |
| R/D | 0.8767 | likely_pathogenic | 0.8053 | pathogenic | -0.118 | Destabilizing | 0.996 | D | 0.439 | neutral | None | None | None | None | I |
| R/E | 0.6228 | likely_pathogenic | 0.5087 | ambiguous | -0.032 | Destabilizing | 0.97 | D | 0.441 | neutral | None | None | None | None | I |
| R/F | 0.9254 | likely_pathogenic | 0.8629 | pathogenic | -0.221 | Destabilizing | 0.999 | D | 0.531 | neutral | None | None | None | None | I |
| R/G | 0.6004 | likely_pathogenic | 0.4439 | ambiguous | -0.396 | Destabilizing | 0.98 | D | 0.459 | neutral | N | 0.489896973 | None | None | I |
| R/H | 0.1773 | likely_benign | 0.1432 | benign | -0.943 | Destabilizing | 0.999 | D | 0.449 | neutral | None | None | None | None | I |
| R/I | 0.735 | likely_pathogenic | 0.6156 | pathogenic | 0.48 | Stabilizing | 0.998 | D | 0.535 | neutral | N | 0.43208082 | None | None | I |
| R/K | 0.1664 | likely_benign | 0.1326 | benign | -0.26 | Destabilizing | 0.122 | N | 0.162 | neutral | N | 0.39313843 | None | None | I |
| R/L | 0.6778 | likely_pathogenic | 0.5707 | pathogenic | 0.48 | Stabilizing | 0.985 | D | 0.459 | neutral | None | None | None | None | I |
| R/M | 0.6957 | likely_pathogenic | 0.5666 | pathogenic | 0.059 | Stabilizing | 1.0 | D | 0.473 | neutral | None | None | None | None | I |
| R/N | 0.791 | likely_pathogenic | 0.6807 | pathogenic | 0.084 | Stabilizing | 0.985 | D | 0.447 | neutral | None | None | None | None | I |
| R/P | 0.9269 | likely_pathogenic | 0.8911 | pathogenic | 0.292 | Stabilizing | 0.999 | D | 0.515 | neutral | None | None | None | None | I |
| R/Q | 0.1611 | likely_benign | 0.1312 | benign | -0.022 | Destabilizing | 0.97 | D | 0.477 | neutral | None | None | None | None | I |
| R/S | 0.7439 | likely_pathogenic | 0.6157 | pathogenic | -0.332 | Destabilizing | 0.961 | D | 0.451 | neutral | N | 0.40889453 | None | None | I |
| R/T | 0.5354 | ambiguous | 0.3941 | ambiguous | -0.093 | Destabilizing | 0.98 | D | 0.463 | neutral | N | 0.389655408 | None | None | I |
| R/V | 0.7687 | likely_pathogenic | 0.6588 | pathogenic | 0.292 | Stabilizing | 0.996 | D | 0.469 | neutral | None | None | None | None | I |
| R/W | 0.5681 | likely_pathogenic | 0.4638 | ambiguous | -0.167 | Destabilizing | 1.0 | D | 0.603 | neutral | None | None | None | None | I |
| R/Y | 0.7919 | likely_pathogenic | 0.6926 | pathogenic | 0.205 | Stabilizing | 0.999 | D | 0.522 | neutral | None | None | 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.