Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17104 | 51535;51536;51537 | chr2:178610216;178610215;178610214 | chr2:179474943;179474942;179474941 |
| N2AB | 15463 | 46612;46613;46614 | chr2:178610216;178610215;178610214 | chr2:179474943;179474942;179474941 |
| N2A | 14536 | 43831;43832;43833 | chr2:178610216;178610215;178610214 | chr2:179474943;179474942;179474941 |
| N2B | 8039 | 24340;24341;24342 | chr2:178610216;178610215;178610214 | chr2:179474943;179474942;179474941 |
| Novex-1 | 8164 | 24715;24716;24717 | chr2:178610216;178610215;178610214 | chr2:179474943;179474942;179474941 |
| Novex-2 | 8231 | 24916;24917;24918 | chr2:178610216;178610215;178610214 | chr2:179474943;179474942;179474941 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | rs1301202997  |
-0.929 | 1.0 | N | 0.7 | 0.492 | 0.699866572147 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| L/P | rs1301202997 |
-0.929 | 1.0 | N | 0.7 | 0.492 | 0.699866572147 | gnomAD-4.0.0 | 1.59279E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4332E-05 | 0 |
| L/R | rs1301202997 |
None | 1.0 | N | 0.711 | 0.469 | 0.659250127719 | gnomAD-4.0.0 | 3.18558E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.5534E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.3455 | ambiguous | 0.4289 | ambiguous | -1.567 | Destabilizing | 0.997 | D | 0.491 | neutral | None | None | None | None | N |
| L/C | 0.535 | ambiguous | 0.6016 | pathogenic | -0.823 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| L/D | 0.7663 | likely_pathogenic | 0.8694 | pathogenic | -0.929 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| L/E | 0.4631 | ambiguous | 0.5955 | pathogenic | -0.797 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| L/F | 0.3249 | likely_benign | 0.4565 | ambiguous | -0.861 | Destabilizing | 1.0 | D | 0.638 | neutral | None | None | None | None | N |
| L/G | 0.5883 | likely_pathogenic | 0.6959 | pathogenic | -1.981 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| L/H | 0.4065 | ambiguous | 0.5354 | ambiguous | -1.06 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| L/I | 0.1445 | likely_benign | 0.1842 | benign | -0.446 | Destabilizing | 0.985 | D | 0.395 | neutral | None | None | None | None | N |
| L/K | 0.3587 | ambiguous | 0.4022 | ambiguous | -0.875 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| L/M | 0.1299 | likely_benign | 0.1491 | benign | -0.427 | Destabilizing | 0.999 | D | 0.65 | neutral | N | 0.51005132 | None | None | N |
| L/N | 0.3074 | likely_benign | 0.412 | ambiguous | -1.03 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| L/P | 0.2999 | likely_benign | 0.404 | ambiguous | -0.793 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | N | 0.483230078 | None | None | N |
| L/Q | 0.1909 | likely_benign | 0.2478 | benign | -0.993 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.507819091 | None | None | N |
| L/R | 0.3138 | likely_benign | 0.3816 | ambiguous | -0.538 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | N | 0.484152797 | None | None | N |
| L/S | 0.3892 | ambiguous | 0.5334 | ambiguous | -1.726 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| L/T | 0.1703 | likely_benign | 0.1883 | benign | -1.455 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| L/V | 0.1272 | likely_benign | 0.1466 | benign | -0.793 | Destabilizing | 0.767 | D | 0.285 | neutral | N | 0.487001102 | None | None | N |
| L/W | 0.5771 | likely_pathogenic | 0.7135 | pathogenic | -1.04 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| L/Y | 0.551 | ambiguous | 0.6869 | pathogenic | -0.726 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | 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.