Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22316 | 67171;67172;67173 | chr2:178580433;178580432;178580431 | chr2:179445160;179445159;179445158 |
| N2AB | 20675 | 62248;62249;62250 | chr2:178580433;178580432;178580431 | chr2:179445160;179445159;179445158 |
| N2A | 19748 | 59467;59468;59469 | chr2:178580433;178580432;178580431 | chr2:179445160;179445159;179445158 |
| N2B | 13251 | 39976;39977;39978 | chr2:178580433;178580432;178580431 | chr2:179445160;179445159;179445158 |
| Novex-1 | 13376 | 40351;40352;40353 | chr2:178580433;178580432;178580431 | chr2:179445160;179445159;179445158 |
| Novex-2 | 13443 | 40552;40553;40554 | chr2:178580433;178580432;178580431 | chr2:179445160;179445159;179445158 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.979 | D | 0.483 | 0.258 | 0.325533332567 | gnomAD-4.0.0 | 6.84438E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99679E-07 | 0 | 0 |
| D/N | rs948813723  |
None | 0.988 | N | 0.72 | 0.306 | 0.30212335484 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| D/N | rs948813723 |
None | 0.988 | N | 0.72 | 0.306 | 0.30212335484 | gnomAD-4.0.0 | 8.67904E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.18696E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.721 | likely_pathogenic | 0.7517 | pathogenic | -0.657 | Destabilizing | 0.919 | D | 0.601 | neutral | N | 0.477800907 | None | None | N |
| D/C | 0.9331 | likely_pathogenic | 0.9454 | pathogenic | -0.3 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| D/E | 0.7489 | likely_pathogenic | 0.7611 | pathogenic | -0.677 | Destabilizing | 0.979 | D | 0.483 | neutral | D | 0.532248681 | None | None | N |
| D/F | 0.9438 | likely_pathogenic | 0.951 | pathogenic | -0.284 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| D/G | 0.8038 | likely_pathogenic | 0.824 | pathogenic | -1.063 | Destabilizing | 0.067 | N | 0.395 | neutral | N | 0.485767029 | None | None | N |
| D/H | 0.8404 | likely_pathogenic | 0.8608 | pathogenic | -0.69 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | N | 0.510278685 | None | None | N |
| D/I | 0.9524 | likely_pathogenic | 0.9596 | pathogenic | 0.44 | Stabilizing | 0.998 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/K | 0.9659 | likely_pathogenic | 0.9722 | pathogenic | -0.658 | Destabilizing | 0.991 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/L | 0.9227 | likely_pathogenic | 0.929 | pathogenic | 0.44 | Stabilizing | 0.995 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/M | 0.9734 | likely_pathogenic | 0.9748 | pathogenic | 1.027 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/N | 0.5725 | likely_pathogenic | 0.5985 | pathogenic | -1.105 | Destabilizing | 0.988 | D | 0.72 | prob.delet. | N | 0.478262267 | None | None | N |
| D/P | 0.9948 | likely_pathogenic | 0.9961 | pathogenic | 0.1 | Stabilizing | 0.998 | D | 0.746 | deleterious | None | None | None | None | N |
| D/Q | 0.9229 | likely_pathogenic | 0.9307 | pathogenic | -0.873 | Destabilizing | 0.998 | D | 0.77 | deleterious | None | None | None | None | N |
| D/R | 0.9558 | likely_pathogenic | 0.9626 | pathogenic | -0.595 | Destabilizing | 0.995 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/S | 0.5405 | ambiguous | 0.5663 | pathogenic | -1.486 | Destabilizing | 0.968 | D | 0.635 | neutral | None | None | None | None | N |
| D/T | 0.8625 | likely_pathogenic | 0.8724 | pathogenic | -1.133 | Destabilizing | 0.995 | D | 0.733 | prob.delet. | None | None | None | None | N |
| D/V | 0.861 | likely_pathogenic | 0.8785 | pathogenic | 0.1 | Stabilizing | 0.994 | D | 0.683 | prob.neutral | N | 0.502563279 | None | None | N |
| D/W | 0.9899 | likely_pathogenic | 0.9916 | pathogenic | -0.188 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| D/Y | 0.7205 | likely_pathogenic | 0.7481 | pathogenic | -0.059 | Destabilizing | 0.999 | D | 0.695 | prob.neutral | N | 0.475070033 | 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.