Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17103 | 51532;51533;51534 | chr2:178610219;178610218;178610217 | chr2:179474946;179474945;179474944 |
| N2AB | 15462 | 46609;46610;46611 | chr2:178610219;178610218;178610217 | chr2:179474946;179474945;179474944 |
| N2A | 14535 | 43828;43829;43830 | chr2:178610219;178610218;178610217 | chr2:179474946;179474945;179474944 |
| N2B | 8038 | 24337;24338;24339 | chr2:178610219;178610218;178610217 | chr2:179474946;179474945;179474944 |
| Novex-1 | 8163 | 24712;24713;24714 | chr2:178610219;178610218;178610217 | chr2:179474946;179474945;179474944 |
| Novex-2 | 8230 | 24913;24914;24915 | chr2:178610219;178610218;178610217 | chr2:179474946;179474945;179474944 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs769721025  |
-0.009 | 0.977 | N | 0.445 | 0.273 | 0.236278675362 | 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 |
| K/E | rs769721025 |
-0.009 | 0.977 | N | 0.445 | 0.273 | 0.236278675362 | gnomAD-4.0.0 | 3.18555E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72315E-06 | 0 | 0 |
| K/R | rs761668415 |
-0.186 | 0.235 | N | 0.235 | 0.072 | 0.24896430686 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| K/R | rs761668415 |
-0.186 | 0.235 | N | 0.235 | 0.072 | 0.24896430686 | gnomAD-4.0.0 | 1.59277E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4332E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.4803 | ambiguous | 0.5705 | pathogenic | -1.141 | Destabilizing | 0.983 | D | 0.556 | neutral | None | None | None | None | N |
| K/C | 0.71 | likely_pathogenic | 0.7714 | pathogenic | -1.043 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| K/D | 0.7807 | likely_pathogenic | 0.8208 | pathogenic | -0.693 | Destabilizing | 0.998 | D | 0.701 | prob.neutral | None | None | None | None | N |
| K/E | 0.362 | ambiguous | 0.4694 | ambiguous | -0.509 | Destabilizing | 0.977 | D | 0.445 | neutral | N | 0.455139399 | None | None | N |
| K/F | 0.8745 | likely_pathogenic | 0.9211 | pathogenic | -0.713 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| K/G | 0.6816 | likely_pathogenic | 0.7361 | pathogenic | -1.51 | Destabilizing | 0.998 | D | 0.614 | neutral | None | None | None | None | N |
| K/H | 0.3671 | ambiguous | 0.4167 | ambiguous | -1.325 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | N |
| K/I | 0.3724 | ambiguous | 0.4936 | ambiguous | -0.144 | Destabilizing | 0.997 | D | 0.713 | prob.delet. | N | 0.51372913 | None | None | N |
| K/L | 0.47 | ambiguous | 0.5606 | ambiguous | -0.144 | Destabilizing | 0.995 | D | 0.614 | neutral | None | None | None | None | N |
| K/M | 0.3327 | likely_benign | 0.4314 | ambiguous | -0.474 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| K/N | 0.5934 | likely_pathogenic | 0.6827 | pathogenic | -0.967 | Destabilizing | 0.993 | D | 0.622 | neutral | N | 0.506456441 | None | None | N |
| K/P | 0.9262 | likely_pathogenic | 0.9291 | pathogenic | -0.453 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | N |
| K/Q | 0.1708 | likely_benign | 0.216 | benign | -0.861 | Destabilizing | 0.993 | D | 0.602 | neutral | N | 0.484406301 | None | None | N |
| K/R | 0.0928 | likely_benign | 0.0985 | benign | -0.5 | Destabilizing | 0.235 | N | 0.235 | neutral | N | 0.483944941 | None | None | N |
| K/S | 0.573 | likely_pathogenic | 0.657 | pathogenic | -1.602 | Destabilizing | 0.983 | D | 0.553 | neutral | None | None | None | None | N |
| K/T | 0.2173 | likely_benign | 0.2917 | benign | -1.192 | Destabilizing | 0.997 | D | 0.668 | neutral | N | 0.466028397 | None | None | N |
| K/V | 0.3233 | likely_benign | 0.4074 | ambiguous | -0.453 | Destabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | N |
| K/W | 0.894 | likely_pathogenic | 0.93 | pathogenic | -0.612 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| K/Y | 0.7601 | likely_pathogenic | 0.8342 | pathogenic | -0.37 | Destabilizing | 0.999 | D | 0.682 | prob.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.