Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18766 | 56521;56522;56523 | chr2:178599605;178599604;178599603 | chr2:179464332;179464331;179464330 |
| N2AB | 17125 | 51598;51599;51600 | chr2:178599605;178599604;178599603 | chr2:179464332;179464331;179464330 |
| N2A | 16198 | 48817;48818;48819 | chr2:178599605;178599604;178599603 | chr2:179464332;179464331;179464330 |
| N2B | 9701 | 29326;29327;29328 | chr2:178599605;178599604;178599603 | chr2:179464332;179464331;179464330 |
| Novex-1 | 9826 | 29701;29702;29703 | chr2:178599605;178599604;178599603 | chr2:179464332;179464331;179464330 |
| Novex-2 | 9893 | 29902;29903;29904 | chr2:178599605;178599604;178599603 | chr2:179464332;179464331;179464330 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | rs727505268  |
-0.757 | 1.0 | D | 0.858 | 0.837 | 0.77335451576 | gnomAD-2.1.1 | 5.32E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 4.40141E-04 | None | 0 | 0 | 0 |
| A/P | rs727505268 |
-0.757 | 1.0 | D | 0.858 | 0.837 | 0.77335451576 | gnomAD-4.0.0 | 3.09292E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.18293E-04 | 1.66389E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7781 | likely_pathogenic | 0.7472 | pathogenic | -1.293 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| A/D | 0.9985 | likely_pathogenic | 0.9962 | pathogenic | -1.478 | Destabilizing | 1.0 | D | 0.868 | deleterious | D | 0.63342867 | None | None | I |
| A/E | 0.9966 | likely_pathogenic | 0.992 | pathogenic | -1.445 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| A/F | 0.988 | likely_pathogenic | 0.9754 | pathogenic | -1.041 | Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | I |
| A/G | 0.393 | ambiguous | 0.3413 | ambiguous | -1.368 | Destabilizing | 1.0 | D | 0.549 | neutral | D | 0.581948838 | None | None | I |
| A/H | 0.9986 | likely_pathogenic | 0.9966 | pathogenic | -1.588 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | I |
| A/I | 0.8418 | likely_pathogenic | 0.7261 | pathogenic | -0.264 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | I |
| A/K | 0.9991 | likely_pathogenic | 0.9978 | pathogenic | -1.259 | Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | I |
| A/L | 0.7421 | likely_pathogenic | 0.6777 | pathogenic | -0.264 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| A/M | 0.8717 | likely_pathogenic | 0.7963 | pathogenic | -0.383 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | I |
| A/N | 0.9958 | likely_pathogenic | 0.9898 | pathogenic | -1.154 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | I |
| A/P | 0.9968 | likely_pathogenic | 0.9932 | pathogenic | -0.479 | Destabilizing | 1.0 | D | 0.858 | deleterious | D | 0.633226866 | None | None | I |
| A/Q | 0.994 | likely_pathogenic | 0.9879 | pathogenic | -1.224 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | I |
| A/R | 0.9968 | likely_pathogenic | 0.9933 | pathogenic | -1.056 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | I |
| A/S | 0.5341 | ambiguous | 0.4186 | ambiguous | -1.587 | Destabilizing | 1.0 | D | 0.559 | neutral | D | 0.616803896 | None | None | I |
| A/T | 0.6402 | likely_pathogenic | 0.4595 | ambiguous | -1.441 | Destabilizing | 1.0 | D | 0.752 | deleterious | D | 0.616602092 | None | None | I |
| A/V | 0.502 | ambiguous | 0.37 | ambiguous | -0.479 | Destabilizing | 1.0 | D | 0.621 | neutral | N | 0.503340782 | None | None | I |
| A/W | 0.9995 | likely_pathogenic | 0.9985 | pathogenic | -1.464 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| A/Y | 0.9969 | likely_pathogenic | 0.9929 | pathogenic | -1.011 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | I |
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.