Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19619 | 59080;59081;59082 | chr2:178593353;178593352;178593351 | chr2:179458080;179458079;179458078 |
| N2AB | 17978 | 54157;54158;54159 | chr2:178593353;178593352;178593351 | chr2:179458080;179458079;179458078 |
| N2A | 17051 | 51376;51377;51378 | chr2:178593353;178593352;178593351 | chr2:179458080;179458079;179458078 |
| N2B | 10554 | 31885;31886;31887 | chr2:178593353;178593352;178593351 | chr2:179458080;179458079;179458078 |
| Novex-1 | 10679 | 32260;32261;32262 | chr2:178593353;178593352;178593351 | chr2:179458080;179458079;179458078 |
| Novex-2 | 10746 | 32461;32462;32463 | chr2:178593353;178593352;178593351 | chr2:179458080;179458079;179458078 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | rs368026488  |
-1.048 | 0.999 | N | 0.443 | 0.125 | 0.412980791724 | gnomAD-2.1.1 | 4.28E-05 | None | None | None | None | N | None | 4.96073E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| E/D | rs368026488 |
-1.048 | 0.999 | N | 0.443 | 0.125 | 0.412980791724 | gnomAD-3.1.2 | 8.55E-05 | None | None | None | None | N | None | 3.13691E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/D | rs368026488 |
-1.048 | 0.999 | N | 0.443 | 0.125 | 0.412980791724 | gnomAD-4.0.0 | 1.3637E-05 | None | None | None | None | N | None | 2.93764E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/Q | rs2050656359 |
None | 1.0 | N | 0.599 | 0.38 | 0.452168903601 | gnomAD-4.0.0 | 1.44039E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.575E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.9084 | likely_pathogenic | 0.8513 | pathogenic | -0.937 | Destabilizing | 0.999 | D | 0.654 | neutral | N | 0.487386352 | None | None | N |
| E/C | 0.9921 | likely_pathogenic | 0.9905 | pathogenic | -0.5 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| E/D | 0.6559 | likely_pathogenic | 0.5881 | pathogenic | -1.053 | Destabilizing | 0.999 | D | 0.443 | neutral | N | 0.497010238 | None | None | N |
| E/F | 0.9965 | likely_pathogenic | 0.9946 | pathogenic | -0.355 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| E/G | 0.8898 | likely_pathogenic | 0.8417 | pathogenic | -1.297 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | N | 0.496794101 | None | None | N |
| E/H | 0.9848 | likely_pathogenic | 0.9768 | pathogenic | -0.599 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| E/I | 0.9808 | likely_pathogenic | 0.9691 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| E/K | 0.9337 | likely_pathogenic | 0.8855 | pathogenic | -0.674 | Destabilizing | 0.999 | D | 0.566 | neutral | N | 0.518865591 | None | None | N |
| E/L | 0.9785 | likely_pathogenic | 0.9609 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| E/M | 0.9774 | likely_pathogenic | 0.9614 | pathogenic | 0.498 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| E/N | 0.95 | likely_pathogenic | 0.9225 | pathogenic | -1.129 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| E/P | 0.9777 | likely_pathogenic | 0.9607 | pathogenic | -0.262 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| E/Q | 0.8283 | likely_pathogenic | 0.7499 | pathogenic | -0.996 | Destabilizing | 1.0 | D | 0.599 | neutral | N | 0.487422351 | None | None | N |
| E/R | 0.953 | likely_pathogenic | 0.9281 | pathogenic | -0.355 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| E/S | 0.9459 | likely_pathogenic | 0.915 | pathogenic | -1.44 | Destabilizing | 0.999 | D | 0.603 | neutral | None | None | None | None | N |
| E/T | 0.9676 | likely_pathogenic | 0.9501 | pathogenic | -1.143 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| E/V | 0.9478 | likely_pathogenic | 0.9174 | pathogenic | -0.262 | Destabilizing | 1.0 | D | 0.759 | deleterious | N | 0.494325339 | None | None | N |
| E/W | 0.9984 | likely_pathogenic | 0.9975 | pathogenic | -0.078 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| E/Y | 0.9922 | likely_pathogenic | 0.9877 | pathogenic | -0.107 | Destabilizing | 1.0 | D | 0.744 | 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.