Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31566 | 94921;94922;94923 | chr2:178546732;178546731;178546730 | chr2:179411459;179411458;179411457 |
| N2AB | 29925 | 89998;89999;90000 | chr2:178546732;178546731;178546730 | chr2:179411459;179411458;179411457 |
| N2A | 28998 | 87217;87218;87219 | chr2:178546732;178546731;178546730 | chr2:179411459;179411458;179411457 |
| N2B | 22501 | 67726;67727;67728 | chr2:178546732;178546731;178546730 | chr2:179411459;179411458;179411457 |
| Novex-1 | 22626 | 68101;68102;68103 | chr2:178546732;178546731;178546730 | chr2:179411459;179411458;179411457 |
| Novex-2 | 22693 | 68302;68303;68304 | chr2:178546732;178546731;178546730 | chr2:179411459;179411458;179411457 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs72648253  |
-0.069 | None | N | 0.091 | 0.117 | 0.104622674875 | gnomAD-2.1.1 | 3.62E-05 | None | None | None | None | I | None | 0 | 2.31924E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65782E-04 |
| D/E | rs72648253 |
-0.069 | None | N | 0.091 | 0.117 | 0.104622674875 | gnomAD-4.0.0 | 1.27301E-05 | None | None | None | None | I | None | 0 | 1.82916E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs1697332587 |
None | 0.773 | D | 0.467 | 0.402 | 0.263612267334 | gnomAD-4.0.0 | 2.73684E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69845E-06 | 0 | 1.65662E-05 |
| D/N | None | None | 0.324 | N | 0.437 | 0.258 | 0.178374595973 | gnomAD-4.0.0 | 1.36842E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99484E-07 | 0 | 1.65662E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3393 | likely_benign | 0.3306 | benign | -0.158 | Destabilizing | 0.193 | N | 0.451 | neutral | N | 0.482576717 | None | None | I |
| D/C | 0.8368 | likely_pathogenic | 0.8388 | pathogenic | -0.181 | Destabilizing | 0.981 | D | 0.535 | neutral | None | None | None | None | I |
| D/E | 0.1162 | likely_benign | 0.113 | benign | -0.371 | Destabilizing | None | N | 0.091 | neutral | N | 0.399248831 | None | None | I |
| D/F | 0.9337 | likely_pathogenic | 0.926 | pathogenic | 0.232 | Stabilizing | 0.932 | D | 0.488 | neutral | None | None | None | None | I |
| D/G | 0.2708 | likely_benign | 0.2741 | benign | -0.413 | Destabilizing | 0.324 | N | 0.458 | neutral | N | 0.484326156 | None | None | I |
| D/H | 0.5654 | likely_pathogenic | 0.5559 | ambiguous | 0.545 | Stabilizing | 0.773 | D | 0.467 | neutral | D | 0.523810051 | None | None | I |
| D/I | 0.8197 | likely_pathogenic | 0.7792 | pathogenic | 0.482 | Stabilizing | 0.818 | D | 0.505 | neutral | None | None | None | None | I |
| D/K | 0.5562 | ambiguous | 0.5247 | ambiguous | 0.304 | Stabilizing | 0.241 | N | 0.446 | neutral | None | None | None | None | I |
| D/L | 0.7796 | likely_pathogenic | 0.7632 | pathogenic | 0.482 | Stabilizing | 0.69 | D | 0.459 | neutral | None | None | None | None | I |
| D/M | 0.8683 | likely_pathogenic | 0.8554 | pathogenic | 0.41 | Stabilizing | 0.981 | D | 0.478 | neutral | None | None | None | None | I |
| D/N | 0.1614 | likely_benign | 0.1498 | benign | -0.296 | Destabilizing | 0.324 | N | 0.437 | neutral | N | 0.500527759 | None | None | I |
| D/P | 0.932 | likely_pathogenic | 0.9247 | pathogenic | 0.292 | Stabilizing | 0.818 | D | 0.471 | neutral | None | None | None | None | I |
| D/Q | 0.4288 | ambiguous | 0.4263 | ambiguous | -0.189 | Destabilizing | 0.241 | N | 0.403 | neutral | None | None | None | None | I |
| D/R | 0.6374 | likely_pathogenic | 0.623 | pathogenic | 0.641 | Stabilizing | 0.69 | D | 0.473 | neutral | None | None | None | None | I |
| D/S | 0.1967 | likely_benign | 0.1972 | benign | -0.387 | Destabilizing | 0.241 | N | 0.416 | neutral | None | None | None | None | I |
| D/T | 0.4268 | ambiguous | 0.4089 | ambiguous | -0.166 | Destabilizing | 0.388 | N | 0.465 | neutral | None | None | None | None | I |
| D/V | 0.5999 | likely_pathogenic | 0.554 | ambiguous | 0.292 | Stabilizing | 0.627 | D | 0.466 | neutral | N | 0.494180577 | None | None | I |
| D/W | 0.9752 | likely_pathogenic | 0.9745 | pathogenic | 0.426 | Stabilizing | 0.981 | D | 0.611 | neutral | None | None | None | None | I |
| D/Y | 0.6775 | likely_pathogenic | 0.6514 | pathogenic | 0.501 | Stabilizing | 0.912 | D | 0.485 | neutral | N | 0.466431261 | 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.