Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14016 | 42271;42272;42273 | chr2:178634828;178634827;178634826 | chr2:179499555;179499554;179499553 |
| N2AB | 12375 | 37348;37349;37350 | chr2:178634828;178634827;178634826 | chr2:179499555;179499554;179499553 |
| N2A | 11448 | 34567;34568;34569 | chr2:178634828;178634827;178634826 | chr2:179499555;179499554;179499553 |
| N2B | 4951 | 15076;15077;15078 | chr2:178634828;178634827;178634826 | chr2:179499555;179499554;179499553 |
| Novex-1 | 5076 | 15451;15452;15453 | chr2:178634828;178634827;178634826 | chr2:179499555;179499554;179499553 |
| Novex-2 | 5143 | 15652;15653;15654 | chr2:178634828;178634827;178634826 | chr2:179499555;179499554;179499553 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/C | None | None | 0.981 | D | 0.697 | 0.393 | 0.464014491786 | gnomAD-4.0.0 | 6.85578E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52666E-05 | None | 0 | 0 | 0 | 0 | 0 |
| G/R | rs367751077  |
-0.347 | 0.531 | D | 0.69 | 0.375 | None | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 0 |
| G/R | rs367751077 |
-0.347 | 0.531 | D | 0.69 | 0.375 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| G/R | rs367751077 |
-0.347 | 0.531 | D | 0.69 | 0.375 | None | gnomAD-4.0.0 | 1.9246E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62955E-05 | 0 | 0 |
| G/S | rs367751077 |
-0.521 | 0.244 | D | 0.653 | 0.408 | 0.218112801441 | gnomAD-2.1.1 | 1.63E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.58E-05 | 0 |
| G/S | rs367751077 |
-0.521 | 0.244 | D | 0.653 | 0.408 | 0.218112801441 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| G/S | rs367751077 |
-0.521 | 0.244 | D | 0.653 | 0.408 | 0.218112801441 | gnomAD-4.0.0 | 1.05543E-05 | None | None | None | None | N | None | 2.67781E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.27236E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.143 | likely_benign | 0.1394 | benign | -0.338 | Destabilizing | 0.244 | N | 0.487 | neutral | D | 0.568589666 | None | None | N |
| G/C | 0.3911 | ambiguous | 0.3503 | ambiguous | -0.927 | Destabilizing | 0.981 | D | 0.697 | prob.delet. | D | 0.574859959 | None | None | N |
| G/D | 0.1134 | likely_benign | 0.1313 | benign | -0.838 | Destabilizing | 0.005 | N | 0.351 | neutral | D | 0.55897425 | None | None | N |
| G/E | 0.1587 | likely_benign | 0.1962 | benign | -1.009 | Destabilizing | 0.003 | N | 0.415 | neutral | None | None | None | None | N |
| G/F | 0.7328 | likely_pathogenic | 0.7457 | pathogenic | -1.081 | Destabilizing | 0.986 | D | 0.739 | deleterious | None | None | None | None | N |
| G/H | 0.4726 | ambiguous | 0.4319 | ambiguous | -0.532 | Destabilizing | 0.958 | D | 0.727 | deleterious | None | None | None | None | N |
| G/I | 0.5448 | ambiguous | 0.5364 | ambiguous | -0.509 | Destabilizing | 0.858 | D | 0.726 | deleterious | None | None | None | None | N |
| G/K | 0.4933 | ambiguous | 0.4288 | ambiguous | -0.913 | Destabilizing | 0.6 | D | 0.631 | neutral | None | None | None | None | N |
| G/L | 0.5564 | ambiguous | 0.559 | ambiguous | -0.509 | Destabilizing | 0.749 | D | 0.714 | prob.delet. | None | None | None | None | N |
| G/M | 0.5653 | likely_pathogenic | 0.5672 | pathogenic | -0.503 | Destabilizing | 0.986 | D | 0.746 | deleterious | None | None | None | None | N |
| G/N | 0.1753 | likely_benign | 0.1574 | benign | -0.562 | Destabilizing | 0.6 | D | 0.685 | prob.delet. | None | None | None | None | N |
| G/P | 0.8288 | likely_pathogenic | 0.8231 | pathogenic | -0.42 | Destabilizing | 0.858 | D | 0.69 | prob.delet. | None | None | None | None | N |
| G/Q | 0.3394 | likely_benign | 0.3287 | benign | -0.89 | Destabilizing | 0.6 | D | 0.683 | prob.neutral | None | None | None | None | N |
| G/R | 0.4553 | ambiguous | 0.3941 | ambiguous | -0.39 | Destabilizing | 0.531 | D | 0.69 | prob.delet. | D | 0.569480539 | None | None | N |
| G/S | 0.1393 | likely_benign | 0.1275 | benign | -0.669 | Destabilizing | 0.244 | N | 0.653 | prob.neutral | D | 0.564636379 | None | None | N |
| G/T | 0.2687 | likely_benign | 0.2637 | benign | -0.779 | Destabilizing | 0.749 | D | 0.699 | prob.delet. | None | None | None | None | N |
| G/V | 0.392 | ambiguous | 0.3805 | ambiguous | -0.42 | Destabilizing | 0.693 | D | 0.712 | prob.delet. | D | 0.573948313 | None | None | N |
| G/W | 0.6168 | likely_pathogenic | 0.6039 | pathogenic | -1.21 | Destabilizing | 0.986 | D | 0.705 | prob.delet. | None | None | None | None | N |
| G/Y | 0.5419 | ambiguous | 0.5114 | ambiguous | -0.88 | Destabilizing | 0.986 | D | 0.743 | deleterious | None | None | 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.