Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17110 | 51553;51554;51555 | chr2:178610198;178610197;178610196 | chr2:179474925;179474924;179474923 |
| N2AB | 15469 | 46630;46631;46632 | chr2:178610198;178610197;178610196 | chr2:179474925;179474924;179474923 |
| N2A | 14542 | 43849;43850;43851 | chr2:178610198;178610197;178610196 | chr2:179474925;179474924;179474923 |
| N2B | 8045 | 24358;24359;24360 | chr2:178610198;178610197;178610196 | chr2:179474925;179474924;179474923 |
| Novex-1 | 8170 | 24733;24734;24735 | chr2:178610198;178610197;178610196 | chr2:179474925;179474924;179474923 |
| Novex-2 | 8237 | 24934;24935;24936 | chr2:178610198;178610197;178610196 | chr2:179474925;179474924;179474923 |
| 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/G | None | None | 1.0 | N | 0.686 | 0.503 | 0.27132560031 | gnomAD-4.0.0 | 1.59281E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86153E-06 | 0 | 0 |
| D/Y | rs1176787179  |
0.153 | 1.0 | N | 0.665 | 0.561 | 0.657092304468 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| D/Y | rs1176787179 |
0.153 | 1.0 | N | 0.665 | 0.561 | 0.657092304468 | gnomAD-4.0.0 | 1.59281E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86151E-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 | 0.8071 | likely_pathogenic | 0.7626 | pathogenic | -0.077 | Destabilizing | 1.0 | D | 0.653 | neutral | N | 0.485331983 | None | None | N |
| D/C | 0.975 | likely_pathogenic | 0.9719 | pathogenic | 0.002 | Stabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| D/E | 0.4615 | ambiguous | 0.4129 | ambiguous | -0.24 | Destabilizing | 1.0 | D | 0.457 | neutral | N | 0.47878705 | None | None | N |
| D/F | 0.9673 | likely_pathogenic | 0.9579 | pathogenic | -0.072 | Destabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | N |
| D/G | 0.6101 | likely_pathogenic | 0.5423 | ambiguous | -0.222 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | N | 0.448978644 | None | None | N |
| D/H | 0.9166 | likely_pathogenic | 0.889 | pathogenic | 0.377 | Stabilizing | 1.0 | D | 0.639 | neutral | N | 0.485331983 | None | None | N |
| D/I | 0.9562 | likely_pathogenic | 0.9457 | pathogenic | 0.244 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| D/K | 0.9612 | likely_pathogenic | 0.9435 | pathogenic | 0.522 | Stabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| D/L | 0.929 | likely_pathogenic | 0.911 | pathogenic | 0.244 | Stabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| D/M | 0.97 | likely_pathogenic | 0.9615 | pathogenic | 0.183 | Stabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| D/N | 0.4527 | ambiguous | 0.4023 | ambiguous | 0.204 | Stabilizing | 1.0 | D | 0.663 | neutral | N | 0.455368686 | None | None | N |
| D/P | 0.9878 | likely_pathogenic | 0.982 | pathogenic | 0.157 | Stabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | N |
| D/Q | 0.9184 | likely_pathogenic | 0.8869 | pathogenic | 0.22 | Stabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | N |
| D/R | 0.9652 | likely_pathogenic | 0.9526 | pathogenic | 0.718 | Stabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | N |
| D/S | 0.6852 | likely_pathogenic | 0.6295 | pathogenic | 0.119 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/T | 0.8641 | likely_pathogenic | 0.833 | pathogenic | 0.239 | Stabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| D/V | 0.877 | likely_pathogenic | 0.8532 | pathogenic | 0.157 | Stabilizing | 1.0 | D | 0.657 | neutral | N | 0.512843987 | None | None | N |
| D/W | 0.9928 | likely_pathogenic | 0.9916 | pathogenic | 0.021 | Stabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | N |
| D/Y | 0.7829 | likely_pathogenic | 0.7575 | pathogenic | 0.169 | Stabilizing | 1.0 | D | 0.665 | neutral | N | 0.501323097 | 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.