Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14523 | 43792;43793;43794 | chr2:178632327;178632326;178632325 | chr2:179497054;179497053;179497052 |
| N2AB | 12882 | 38869;38870;38871 | chr2:178632327;178632326;178632325 | chr2:179497054;179497053;179497052 |
| N2A | 11955 | 36088;36089;36090 | chr2:178632327;178632326;178632325 | chr2:179497054;179497053;179497052 |
| N2B | 5458 | 16597;16598;16599 | chr2:178632327;178632326;178632325 | chr2:179497054;179497053;179497052 |
| Novex-1 | 5583 | 16972;16973;16974 | chr2:178632327;178632326;178632325 | chr2:179497054;179497053;179497052 |
| Novex-2 | 5650 | 17173;17174;17175 | chr2:178632327;178632326;178632325 | chr2:179497054;179497053;179497052 |
| 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 | rs758154539  |
-0.047 | 0.02 | N | 0.301 | 0.277 | 0.124217242631 | gnomAD-2.1.1 | 8.44E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.44E-05 | None | 0 | 9.37E-06 | 0 |
| D/E | rs758154539 |
-0.047 | 0.02 | N | 0.301 | 0.277 | 0.124217242631 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07039E-04 | 0 |
| D/E | rs758154539 |
-0.047 | 0.02 | N | 0.301 | 0.277 | 0.124217242631 | gnomAD-4.0.0 | 4.97754E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54966E-06 | 5.5605E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3714 | ambiguous | 0.3526 | ambiguous | -0.314 | Destabilizing | 0.939 | D | 0.626 | neutral | D | 0.540463877 | None | None | N |
| D/C | 0.8658 | likely_pathogenic | 0.857 | pathogenic | 0.009 | Stabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | N |
| D/E | 0.2687 | likely_benign | 0.2386 | benign | -0.466 | Destabilizing | 0.02 | N | 0.301 | neutral | N | 0.399549553 | None | None | N |
| D/F | 0.8804 | likely_pathogenic | 0.8694 | pathogenic | -0.27 | Destabilizing | 0.998 | D | 0.679 | prob.neutral | None | None | None | None | N |
| D/G | 0.298 | likely_benign | 0.2924 | benign | -0.55 | Destabilizing | 0.939 | D | 0.629 | neutral | D | 0.526085275 | None | None | N |
| D/H | 0.5034 | ambiguous | 0.4928 | ambiguous | -0.343 | Destabilizing | 0.998 | D | 0.577 | neutral | D | 0.544830637 | None | None | N |
| D/I | 0.7496 | likely_pathogenic | 0.7359 | pathogenic | 0.269 | Stabilizing | 0.993 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/K | 0.563 | ambiguous | 0.5422 | ambiguous | 0.012 | Stabilizing | 0.91 | D | 0.608 | neutral | None | None | None | None | N |
| D/L | 0.7325 | likely_pathogenic | 0.7199 | pathogenic | 0.269 | Stabilizing | 0.986 | D | 0.663 | neutral | None | None | None | None | N |
| D/M | 0.905 | likely_pathogenic | 0.891 | pathogenic | 0.501 | Stabilizing | 0.999 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/N | 0.1589 | likely_benign | 0.1481 | benign | -0.203 | Destabilizing | 0.939 | D | 0.593 | neutral | D | 0.576508666 | None | None | N |
| D/P | 0.7945 | likely_pathogenic | 0.7786 | pathogenic | 0.098 | Stabilizing | 0.993 | D | 0.581 | neutral | None | None | None | None | N |
| D/Q | 0.5761 | likely_pathogenic | 0.5519 | ambiguous | -0.157 | Destabilizing | 0.973 | D | 0.551 | neutral | None | None | None | None | N |
| D/R | 0.5803 | likely_pathogenic | 0.5722 | pathogenic | 0.162 | Stabilizing | 0.986 | D | 0.642 | neutral | None | None | None | None | N |
| D/S | 0.2224 | likely_benign | 0.2112 | benign | -0.35 | Destabilizing | 0.953 | D | 0.575 | neutral | None | None | None | None | N |
| D/T | 0.5281 | ambiguous | 0.4962 | ambiguous | -0.175 | Destabilizing | 0.986 | D | 0.563 | neutral | None | None | None | None | N |
| D/V | 0.533 | ambiguous | 0.5206 | ambiguous | 0.098 | Stabilizing | 0.991 | D | 0.65 | neutral | D | 0.549362257 | None | None | N |
| D/W | 0.9673 | likely_pathogenic | 0.9656 | pathogenic | -0.171 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/Y | 0.4542 | ambiguous | 0.4633 | ambiguous | -0.054 | Destabilizing | 0.997 | D | 0.679 | prob.neutral | D | 0.575422865 | 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.