Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21639 | 65140;65141;65142 | chr2:178584726;178584725;178584724 | chr2:179449453;179449452;179449451 |
| N2AB | 19998 | 60217;60218;60219 | chr2:178584726;178584725;178584724 | chr2:179449453;179449452;179449451 |
| N2A | 19071 | 57436;57437;57438 | chr2:178584726;178584725;178584724 | chr2:179449453;179449452;179449451 |
| N2B | 12574 | 37945;37946;37947 | chr2:178584726;178584725;178584724 | chr2:179449453;179449452;179449451 |
| Novex-1 | 12699 | 38320;38321;38322 | chr2:178584726;178584725;178584724 | chr2:179449453;179449452;179449451 |
| Novex-2 | 12766 | 38521;38522;38523 | chr2:178584726;178584725;178584724 | chr2:179449453;179449452;179449451 |
| 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/G | rs1432889079  |
None | 1.0 | N | 0.579 | 0.373 | None | gnomAD-4.0.0 | 2.053E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69885E-06 | 0 | 0 |
| R/Q | rs373282633 |
0.116 | 1.0 | N | 0.681 | 0.322 | None | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | I | None | 4.13E-05 | 2.83E-05 | None | 0 | 5.13E-05 | None | 0 | None | 0 | 4.7E-05 | 0 |
| R/Q | rs373282633 |
0.116 | 1.0 | N | 0.681 | 0.322 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs373282633 |
0.116 | 1.0 | N | 0.681 | 0.322 | None | gnomAD-4.0.0 | 4.40076E-05 | None | None | None | None | I | None | 1.3354E-05 | 1.6675E-05 | None | 0 | 2.23055E-04 | None | 0 | 0 | 4.74744E-05 | 0 | 4.80492E-05 |
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 | 0.927 | likely_pathogenic | 0.9227 | pathogenic | -0.026 | Destabilizing | 0.999 | D | 0.613 | neutral | None | None | None | None | I |
| R/C | 0.6453 | likely_pathogenic | 0.6416 | pathogenic | -0.324 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| R/D | 0.974 | likely_pathogenic | 0.9721 | pathogenic | -0.23 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| R/E | 0.9224 | likely_pathogenic | 0.9024 | pathogenic | -0.173 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | I |
| R/F | 0.9638 | likely_pathogenic | 0.9592 | pathogenic | -0.365 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | I |
| R/G | 0.9079 | likely_pathogenic | 0.9169 | pathogenic | -0.181 | Destabilizing | 1.0 | D | 0.579 | neutral | N | 0.517897225 | None | None | I |
| R/H | 0.4548 | ambiguous | 0.446 | ambiguous | -0.805 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| R/I | 0.8188 | likely_pathogenic | 0.7703 | pathogenic | 0.34 | Stabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| R/K | 0.3689 | ambiguous | 0.3102 | benign | -0.18 | Destabilizing | 0.998 | D | 0.456 | neutral | None | None | None | None | I |
| R/L | 0.802 | likely_pathogenic | 0.8 | pathogenic | 0.34 | Stabilizing | 1.0 | D | 0.579 | neutral | N | 0.50018383 | None | None | I |
| R/M | 0.8903 | likely_pathogenic | 0.8707 | pathogenic | -0.141 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| R/N | 0.9534 | likely_pathogenic | 0.9491 | pathogenic | -0.141 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | I |
| R/P | 0.9462 | likely_pathogenic | 0.9432 | pathogenic | 0.237 | Stabilizing | 1.0 | D | 0.648 | neutral | N | 0.503954853 | None | None | I |
| R/Q | 0.4885 | ambiguous | 0.4413 | ambiguous | -0.151 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | N | 0.49718081 | None | None | I |
| R/S | 0.9482 | likely_pathogenic | 0.9447 | pathogenic | -0.358 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | I |
| R/T | 0.9032 | likely_pathogenic | 0.8796 | pathogenic | -0.178 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | I |
| R/V | 0.8786 | likely_pathogenic | 0.8499 | pathogenic | 0.237 | Stabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| R/W | 0.7848 | likely_pathogenic | 0.7905 | pathogenic | -0.542 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| R/Y | 0.8793 | likely_pathogenic | 0.8692 | pathogenic | -0.117 | Destabilizing | 1.0 | D | 0.688 | prob.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.