Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2984 | 9175;9176;9177 | chr2:178768886;178768885;178768884 | chr2:179633613;179633612;179633611 |
| N2AB | 2984 | 9175;9176;9177 | chr2:178768886;178768885;178768884 | chr2:179633613;179633612;179633611 |
| N2A | 2984 | 9175;9176;9177 | chr2:178768886;178768885;178768884 | chr2:179633613;179633612;179633611 |
| N2B | 2938 | 9037;9038;9039 | chr2:178768886;178768885;178768884 | chr2:179633613;179633612;179633611 |
| Novex-1 | 2938 | 9037;9038;9039 | chr2:178768886;178768885;178768884 | chr2:179633613;179633612;179633611 |
| Novex-2 | 2938 | 9037;9038;9039 | chr2:178768886;178768885;178768884 | chr2:179633613;179633612;179633611 |
| Novex-3 | 2984 | 9175;9176;9177 | chr2:178768886;178768885;178768884 | chr2:179633613;179633612;179633611 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs2090998347  |
None | 1.0 | D | 0.663 | 0.393 | 0.202086224978 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs2090998347 |
None | 1.0 | D | 0.663 | 0.393 | 0.202086224978 | gnomAD-4.0.0 | 3.09815E-06 | None | None | None | None | N | None | 1.33518E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.38982E-06 | 0 | 0 |
| D/Y | rs2090998347 |
None | 1.0 | D | 0.774 | 0.631 | 0.54626238531 | gnomAD-4.0.0 | 4.10473E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39582E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.8974 | likely_pathogenic | 0.8557 | pathogenic | -0.359 | Destabilizing | 1.0 | D | 0.769 | deleterious | N | 0.444360421 | None | None | N |
| D/C | 0.995 | likely_pathogenic | 0.9941 | pathogenic | 0.08 | Stabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| D/E | 0.8423 | likely_pathogenic | 0.7559 | pathogenic | -0.578 | Destabilizing | 1.0 | D | 0.441 | neutral | N | 0.442000539 | None | None | N |
| D/F | 0.9931 | likely_pathogenic | 0.9916 | pathogenic | -0.464 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| D/G | 0.8658 | likely_pathogenic | 0.81 | pathogenic | -0.614 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | N | 0.433251521 | None | None | N |
| D/H | 0.9657 | likely_pathogenic | 0.9588 | pathogenic | -0.76 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.479153428 | None | None | N |
| D/I | 0.9927 | likely_pathogenic | 0.988 | pathogenic | 0.278 | Stabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| D/K | 0.9733 | likely_pathogenic | 0.9669 | pathogenic | 0.022 | Stabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| D/L | 0.9828 | likely_pathogenic | 0.9764 | pathogenic | 0.278 | Stabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| D/M | 0.9915 | likely_pathogenic | 0.9888 | pathogenic | 0.68 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| D/N | 0.6939 | likely_pathogenic | 0.6394 | pathogenic | -0.234 | Destabilizing | 1.0 | D | 0.663 | neutral | D | 0.539403887 | None | None | N |
| D/P | 0.9994 | likely_pathogenic | 0.999 | pathogenic | 0.09 | Stabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| D/Q | 0.9614 | likely_pathogenic | 0.9449 | pathogenic | -0.185 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| D/R | 0.9836 | likely_pathogenic | 0.977 | pathogenic | 0.006 | Stabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| D/S | 0.8439 | likely_pathogenic | 0.7928 | pathogenic | -0.391 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/T | 0.9705 | likely_pathogenic | 0.9543 | pathogenic | -0.194 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| D/V | 0.9714 | likely_pathogenic | 0.9544 | pathogenic | 0.09 | Stabilizing | 1.0 | D | 0.809 | deleterious | D | 0.545779634 | None | None | N |
| D/W | 0.9985 | likely_pathogenic | 0.9982 | pathogenic | -0.409 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| D/Y | 0.9264 | likely_pathogenic | 0.9096 | pathogenic | -0.25 | Destabilizing | 1.0 | D | 0.774 | deleterious | D | 0.545087972 | 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.