Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16466 | 49621;49622;49623 | chr2:178613887;178613886;178613885 | chr2:179478614;179478613;179478612 |
| N2AB | 14825 | 44698;44699;44700 | chr2:178613887;178613886;178613885 | chr2:179478614;179478613;179478612 |
| N2A | 13898 | 41917;41918;41919 | chr2:178613887;178613886;178613885 | chr2:179478614;179478613;179478612 |
| N2B | 7401 | 22426;22427;22428 | chr2:178613887;178613886;178613885 | chr2:179478614;179478613;179478612 |
| Novex-1 | 7526 | 22801;22802;22803 | chr2:178613887;178613886;178613885 | chr2:179478614;179478613;179478612 |
| Novex-2 | 7593 | 23002;23003;23004 | chr2:178613887;178613886;178613885 | chr2:179478614;179478613;179478612 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | None | None | 0.062 | N | 0.247 | 0.112 | 0.110078149338 | gnomAD-4.0.0 | 6.85563E-07 | None | None | None | None | N | None | 3.00012E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs755998484  |
-1.792 | 0.929 | N | 0.455 | 0.102 | 0.239901079897 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| A/T | rs755998484 |
-1.792 | 0.929 | N | 0.455 | 0.102 | 0.239901079897 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/T | rs755998484 |
-1.792 | 0.929 | N | 0.455 | 0.102 | 0.239901079897 | gnomAD-4.0.0 | 2.48357E-06 | None | None | None | None | N | None | 0 | 1.67678E-05 | None | 0 | 0 | None | 0 | 0 | 2.54601E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.427 | ambiguous | 0.3944 | ambiguous | -1.692 | Destabilizing | 0.998 | D | 0.657 | neutral | None | None | None | None | N |
| A/D | 0.8657 | likely_pathogenic | 0.87 | pathogenic | -2.485 | Highly Destabilizing | 0.956 | D | 0.741 | deleterious | None | None | None | None | N |
| A/E | 0.7849 | likely_pathogenic | 0.8011 | pathogenic | -2.409 | Highly Destabilizing | 0.822 | D | 0.677 | prob.neutral | N | 0.47912304 | None | None | N |
| A/F | 0.5564 | ambiguous | 0.5857 | pathogenic | -1.097 | Destabilizing | 0.978 | D | 0.773 | deleterious | None | None | None | None | N |
| A/G | 0.21 | likely_benign | 0.186 | benign | -1.63 | Destabilizing | 0.489 | N | 0.481 | neutral | N | 0.460440471 | None | None | N |
| A/H | 0.7514 | likely_pathogenic | 0.7368 | pathogenic | -1.673 | Destabilizing | 0.994 | D | 0.762 | deleterious | None | None | None | None | N |
| A/I | 0.6325 | likely_pathogenic | 0.6543 | pathogenic | -0.448 | Destabilizing | 0.978 | D | 0.749 | deleterious | None | None | None | None | N |
| A/K | 0.9453 | likely_pathogenic | 0.9511 | pathogenic | -1.483 | Destabilizing | 0.754 | D | 0.673 | neutral | None | None | None | None | N |
| A/L | 0.504 | ambiguous | 0.5126 | ambiguous | -0.448 | Destabilizing | 0.86 | D | 0.655 | neutral | None | None | None | None | N |
| A/M | 0.3969 | ambiguous | 0.3996 | ambiguous | -0.699 | Destabilizing | 0.998 | D | 0.736 | prob.delet. | None | None | None | None | N |
| A/N | 0.5882 | likely_pathogenic | 0.5727 | pathogenic | -1.591 | Destabilizing | 0.915 | D | 0.746 | deleterious | None | None | None | None | N |
| A/P | 0.9926 | likely_pathogenic | 0.9938 | pathogenic | -0.689 | Destabilizing | 0.988 | D | 0.744 | deleterious | D | 0.583604406 | None | None | N |
| A/Q | 0.7192 | likely_pathogenic | 0.6975 | pathogenic | -1.655 | Destabilizing | 0.956 | D | 0.773 | deleterious | None | None | None | None | N |
| A/R | 0.8934 | likely_pathogenic | 0.903 | pathogenic | -1.234 | Destabilizing | 0.956 | D | 0.763 | deleterious | None | None | None | None | N |
| A/S | 0.0975 | likely_benign | 0.0952 | benign | -1.96 | Destabilizing | 0.062 | N | 0.247 | neutral | N | 0.346340293 | None | None | N |
| A/T | 0.1556 | likely_benign | 0.1707 | benign | -1.785 | Destabilizing | 0.929 | D | 0.455 | neutral | N | 0.434278218 | None | None | N |
| A/V | 0.3845 | ambiguous | 0.4129 | ambiguous | -0.689 | Destabilizing | 0.822 | D | 0.522 | neutral | N | 0.480746741 | None | None | N |
| A/W | 0.9104 | likely_pathogenic | 0.9217 | pathogenic | -1.566 | Destabilizing | 0.998 | D | 0.751 | deleterious | None | None | None | None | N |
| A/Y | 0.7071 | likely_pathogenic | 0.7269 | pathogenic | -1.138 | Destabilizing | 0.993 | D | 0.773 | 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.