Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2415 | 7468;7469;7470 | chr2:178773925;178773924;178773923 | chr2:179638652;179638651;179638650 |
| N2AB | 2415 | 7468;7469;7470 | chr2:178773925;178773924;178773923 | chr2:179638652;179638651;179638650 |
| N2A | 2415 | 7468;7469;7470 | chr2:178773925;178773924;178773923 | chr2:179638652;179638651;179638650 |
| N2B | 2369 | 7330;7331;7332 | chr2:178773925;178773924;178773923 | chr2:179638652;179638651;179638650 |
| Novex-1 | 2369 | 7330;7331;7332 | chr2:178773925;178773924;178773923 | chr2:179638652;179638651;179638650 |
| Novex-2 | 2369 | 7330;7331;7332 | chr2:178773925;178773924;178773923 | chr2:179638652;179638651;179638650 |
| Novex-3 | 2415 | 7468;7469;7470 | chr2:178773925;178773924;178773923 | chr2:179638652;179638651;179638650 |
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 | None | None | 0.999 | N | 0.415 | 0.274 | 0.242825505644 | gnomAD-4.0.0 | 3.18109E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.76554E-05 | 0 | None | 1.88175E-05 | 0 | 0 | 0 | 0 |
| E/V | rs1462312746  |
None | 1.0 | N | 0.631 | 0.625 | 0.678036545427 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| E/V | rs1462312746 |
None | 1.0 | N | 0.631 | 0.625 | 0.678036545427 | gnomAD-4.0.0 | 4.95669E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.77971E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.6002 | likely_pathogenic | 0.6185 | pathogenic | -0.76 | Destabilizing | 0.999 | D | 0.581 | neutral | N | 0.507247168 | None | None | N |
| E/C | 0.9833 | likely_pathogenic | 0.985 | pathogenic | -0.516 | Destabilizing | 1.0 | D | 0.615 | neutral | None | None | None | None | N |
| E/D | 0.5991 | likely_pathogenic | 0.6208 | pathogenic | -1.201 | Destabilizing | 0.999 | D | 0.415 | neutral | N | 0.49795071 | None | None | N |
| E/F | 0.9849 | likely_pathogenic | 0.9865 | pathogenic | -0.277 | Destabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | N |
| E/G | 0.5889 | likely_pathogenic | 0.6165 | pathogenic | -1.139 | Destabilizing | 1.0 | D | 0.607 | neutral | N | 0.502881326 | None | None | N |
| E/H | 0.8925 | likely_pathogenic | 0.8993 | pathogenic | -0.72 | Destabilizing | 1.0 | D | 0.573 | neutral | None | None | None | None | N |
| E/I | 0.9296 | likely_pathogenic | 0.9363 | pathogenic | 0.273 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| E/K | 0.5368 | ambiguous | 0.5599 | ambiguous | -0.893 | Destabilizing | 0.999 | D | 0.54 | neutral | N | 0.497982586 | None | None | N |
| E/L | 0.9191 | likely_pathogenic | 0.9213 | pathogenic | 0.273 | Stabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | N |
| E/M | 0.9114 | likely_pathogenic | 0.917 | pathogenic | 0.734 | Stabilizing | 1.0 | D | 0.561 | neutral | None | None | None | None | N |
| E/N | 0.7877 | likely_pathogenic | 0.8065 | pathogenic | -1.28 | Destabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | N |
| E/P | 0.974 | likely_pathogenic | 0.9735 | pathogenic | -0.049 | Destabilizing | 1.0 | D | 0.612 | neutral | None | None | None | None | N |
| E/Q | 0.4006 | ambiguous | 0.4081 | ambiguous | -1.106 | Destabilizing | 1.0 | D | 0.541 | neutral | N | 0.490556949 | None | None | N |
| E/R | 0.6793 | likely_pathogenic | 0.693 | pathogenic | -0.667 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| E/S | 0.6399 | likely_pathogenic | 0.6586 | pathogenic | -1.608 | Destabilizing | 0.999 | D | 0.57 | neutral | None | None | None | None | N |
| E/T | 0.6879 | likely_pathogenic | 0.7135 | pathogenic | -1.3 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | N |
| E/V | 0.7958 | likely_pathogenic | 0.8135 | pathogenic | -0.049 | Destabilizing | 1.0 | D | 0.631 | neutral | N | 0.513977747 | None | None | N |
| E/W | 0.9936 | likely_pathogenic | 0.9941 | pathogenic | -0.13 | Destabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | N |
| E/Y | 0.9646 | likely_pathogenic | 0.9671 | pathogenic | -0.08 | Destabilizing | 1.0 | D | 0.599 | neutral | 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.