Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 190 | 793;794;795 | chr2:178800410;178800409;178800408 | chr2:179665137;179665136;179665135 |
| N2AB | 190 | 793;794;795 | chr2:178800410;178800409;178800408 | chr2:179665137;179665136;179665135 |
| N2A | 190 | 793;794;795 | chr2:178800410;178800409;178800408 | chr2:179665137;179665136;179665135 |
| N2B | 190 | 793;794;795 | chr2:178800410;178800409;178800408 | chr2:179665137;179665136;179665135 |
| Novex-1 | 190 | 793;794;795 | chr2:178800410;178800409;178800408 | chr2:179665137;179665136;179665135 |
| Novex-2 | 190 | 793;794;795 | chr2:178800410;178800409;178800408 | chr2:179665137;179665136;179665135 |
| Novex-3 | 190 | 793;794;795 | chr2:178800410;178800409;178800408 | chr2:179665137;179665136;179665135 |
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 | rs753196873  |
-0.643 | 0.001 | N | 0.352 | 0.086 | 0.24107899 | gnomAD-2.1.1 | 7.96E-06 | None | None | None | -1.078(TCAP) | N | None | 6.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.8E-06 | 0 |
| E/D | rs753196873 |
-0.643 | 0.001 | N | 0.352 | 0.086 | 0.24107899 | gnomAD-3.1.2 | 5.91E-05 | None | None | None | -1.078(TCAP) | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| E/D | rs753196873 |
-0.643 | 0.001 | N | 0.352 | 0.086 | 0.24107899 | gnomAD-4.0.0 | 1.36305E-05 | None | None | None | -1.078(TCAP) | N | None | 6.67254E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44069E-05 | 0 | 0 |
| E/Q | None | None | 0.306 | N | 0.315 | 0.262 | 0.24166428 | gnomAD-4.0.0 | 1.59053E-06 | None | None | None | -1.563(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43295E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.4945 | ambiguous | 0.6547 | pathogenic | -0.843 | Destabilizing | 0.787 | D | 0.642 | neutral | N | 0.50429845 | None | -1.234(TCAP) | N |
| E/C | 0.9868 | likely_pathogenic | 0.9933 | pathogenic | -0.168 | Destabilizing | 0.998 | D | 0.671 | neutral | None | None | None | -1.076(TCAP) | N |
| E/D | 0.3673 | ambiguous | 0.6074 | pathogenic | -0.566 | Destabilizing | 0.001 | N | 0.352 | neutral | N | 0.494016 | None | -1.078(TCAP) | N |
| E/F | 0.9575 | likely_pathogenic | 0.9821 | pathogenic | -0.587 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | -0.903(TCAP) | N |
| E/G | 0.7512 | likely_pathogenic | 0.866 | pathogenic | -1.095 | Destabilizing | 0.925 | D | 0.691 | prob.neutral | N | 0.5084126 | None | -1.44(TCAP) | N |
| E/H | 0.8407 | likely_pathogenic | 0.9113 | pathogenic | -0.648 | Destabilizing | 0.994 | D | 0.655 | neutral | None | None | None | 0.038(TCAP) | N |
| E/I | 0.7617 | likely_pathogenic | 0.869 | pathogenic | -0.187 | Destabilizing | 0.968 | D | 0.749 | deleterious | None | None | None | -0.625(TCAP) | N |
| E/K | 0.5482 | ambiguous | 0.6789 | pathogenic | 0.092 | Stabilizing | 0.774 | D | 0.585 | neutral | N | 0.4168948 | None | -1.033(TCAP) | N |
| E/L | 0.8209 | likely_pathogenic | 0.9011 | pathogenic | -0.187 | Destabilizing | 0.968 | D | 0.726 | prob.delet. | None | None | None | -0.625(TCAP) | N |
| E/M | 0.8361 | likely_pathogenic | 0.9065 | pathogenic | 0.173 | Stabilizing | 0.984 | D | 0.723 | prob.delet. | None | None | None | 0.094(TCAP) | N |
| E/N | 0.6332 | likely_pathogenic | 0.795 | pathogenic | -0.341 | Destabilizing | 0.776 | D | 0.655 | neutral | None | None | None | -1.946(TCAP) | N |
| E/P | 0.9491 | likely_pathogenic | 0.9809 | pathogenic | -0.386 | Destabilizing | 0.818 | D | 0.749 | deleterious | None | None | None | -0.822(TCAP) | N |
| E/Q | 0.3235 | likely_benign | 0.405 | ambiguous | -0.29 | Destabilizing | 0.306 | N | 0.315 | neutral | N | 0.454077 | None | -1.563(TCAP) | N |
| E/R | 0.6667 | likely_pathogenic | 0.7964 | pathogenic | 0.222 | Stabilizing | 0.97 | D | 0.647 | neutral | None | None | None | -0.84(TCAP) | N |
| E/S | 0.4965 | ambiguous | 0.6471 | pathogenic | -0.536 | Destabilizing | 0.83 | D | 0.601 | neutral | None | None | None | -2.095(TCAP) | N |
| E/T | 0.4968 | ambiguous | 0.657 | pathogenic | -0.318 | Destabilizing | 0.96 | D | 0.725 | prob.delet. | None | None | None | -1.895(TCAP) | N |
| E/V | 0.5455 | ambiguous | 0.6904 | pathogenic | -0.386 | Destabilizing | 0.942 | D | 0.732 | prob.delet. | N | 0.4999289 | None | -0.822(TCAP) | N |
| E/W | 0.9901 | likely_pathogenic | 0.9962 | pathogenic | -0.325 | Destabilizing | 0.999 | D | 0.664 | neutral | None | None | None | -0.907(TCAP) | N |
| E/Y | 0.9304 | likely_pathogenic | 0.9701 | pathogenic | -0.315 | Destabilizing | 0.998 | D | 0.745 | deleterious | None | None | None | -0.784(TCAP) | 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.