Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22574 | 67945;67946;67947 | chr2:178579310;178579309;178579308 | chr2:179444037;179444036;179444035 |
| N2AB | 20933 | 63022;63023;63024 | chr2:178579310;178579309;178579308 | chr2:179444037;179444036;179444035 |
| N2A | 20006 | 60241;60242;60243 | chr2:178579310;178579309;178579308 | chr2:179444037;179444036;179444035 |
| N2B | 13509 | 40750;40751;40752 | chr2:178579310;178579309;178579308 | chr2:179444037;179444036;179444035 |
| Novex-1 | 13634 | 41125;41126;41127 | chr2:178579310;178579309;178579308 | chr2:179444037;179444036;179444035 |
| Novex-2 | 13701 | 41326;41327;41328 | chr2:178579310;178579309;178579308 | chr2:179444037;179444036;179444035 |
| 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/M | None | None | 0.267 | N | 0.315 | 0.24 | 0.236890367714 | gnomAD-4.0.0 | 6.85482E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00812E-07 | 0 | 0 |
| I/V | rs754723277  |
-1.115 | 0.022 | N | 0.209 | 0.08 | 0.349204839081 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| I/V | rs754723277 |
-1.115 | 0.022 | N | 0.209 | 0.08 | 0.349204839081 | gnomAD-4.0.0 | 3.19679E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87221E-06 | 1.43579E-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 | 0.8068 | likely_pathogenic | 0.7818 | pathogenic | -1.998 | Destabilizing | 0.688 | D | 0.511 | neutral | None | None | None | None | I |
| I/C | 0.843 | likely_pathogenic | 0.8412 | pathogenic | -1.26 | Destabilizing | 0.998 | D | 0.625 | neutral | None | None | None | None | I |
| I/D | 0.9962 | likely_pathogenic | 0.9955 | pathogenic | -1.51 | Destabilizing | 0.991 | D | 0.697 | prob.neutral | None | None | None | None | I |
| I/E | 0.9823 | likely_pathogenic | 0.9789 | pathogenic | -1.474 | Destabilizing | 0.974 | D | 0.685 | prob.neutral | None | None | None | None | I |
| I/F | 0.2653 | likely_benign | 0.2648 | benign | -1.393 | Destabilizing | 0.949 | D | 0.598 | neutral | None | None | None | None | I |
| I/G | 0.9605 | likely_pathogenic | 0.9522 | pathogenic | -2.371 | Highly Destabilizing | 0.974 | D | 0.685 | prob.neutral | None | None | None | None | I |
| I/H | 0.9515 | likely_pathogenic | 0.9495 | pathogenic | -1.592 | Destabilizing | 0.998 | D | 0.704 | prob.neutral | None | None | None | None | I |
| I/K | 0.949 | likely_pathogenic | 0.9432 | pathogenic | -1.491 | Destabilizing | 0.934 | D | 0.684 | prob.neutral | N | 0.500539171 | None | None | I |
| I/L | 0.1924 | likely_benign | 0.1889 | benign | -1.022 | Destabilizing | 0.111 | N | 0.292 | neutral | D | 0.539353585 | None | None | I |
| I/M | 0.1745 | likely_benign | 0.1619 | benign | -0.77 | Destabilizing | 0.267 | N | 0.315 | neutral | N | 0.504805132 | None | None | I |
| I/N | 0.9423 | likely_pathogenic | 0.9393 | pathogenic | -1.331 | Destabilizing | 0.991 | D | 0.711 | prob.delet. | None | None | None | None | I |
| I/P | 0.9886 | likely_pathogenic | 0.987 | pathogenic | -1.317 | Destabilizing | 0.991 | D | 0.707 | prob.neutral | None | None | None | None | I |
| I/Q | 0.9405 | likely_pathogenic | 0.9313 | pathogenic | -1.471 | Destabilizing | 0.974 | D | 0.711 | prob.delet. | None | None | None | None | I |
| I/R | 0.9166 | likely_pathogenic | 0.9102 | pathogenic | -0.886 | Destabilizing | 0.966 | D | 0.711 | prob.delet. | D | 0.523416366 | None | None | I |
| I/S | 0.8735 | likely_pathogenic | 0.8659 | pathogenic | -1.979 | Destabilizing | 0.915 | D | 0.623 | neutral | None | None | None | None | I |
| I/T | 0.8202 | likely_pathogenic | 0.8258 | pathogenic | -1.819 | Destabilizing | 0.801 | D | 0.575 | neutral | D | 0.533601049 | None | None | I |
| I/V | 0.0801 | likely_benign | 0.0778 | benign | -1.317 | Destabilizing | 0.022 | N | 0.209 | neutral | N | 0.447258996 | None | None | I |
| I/W | 0.9323 | likely_pathogenic | 0.9243 | pathogenic | -1.497 | Destabilizing | 0.998 | D | 0.714 | prob.delet. | None | None | None | None | I |
| I/Y | 0.7437 | likely_pathogenic | 0.7498 | pathogenic | -1.293 | Destabilizing | 0.974 | D | 0.648 | 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.