Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8325 | 25198;25199;25200 | chr2:178718033;178718032;178718031 | chr2:179582760;179582759;179582758 |
| N2AB | 8008 | 24247;24248;24249 | chr2:178718033;178718032;178718031 | chr2:179582760;179582759;179582758 |
| N2A | 7081 | 21466;21467;21468 | chr2:178718033;178718032;178718031 | chr2:179582760;179582759;179582758 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 | rs72648984  |
0.424 | 0.216 | N | 0.212 | 0.194 | None | gnomAD-2.1.1 | 5.58292E-03 | None | None | None | None | I | None | 1.32253E-03 | 4.80715E-04 | None | 2.89967E-04 | 0 | None | 0 | None | 1.51854E-02 | 8.58054E-03 | 4.77394E-03 |
| K/E | rs72648984 |
0.424 | 0.216 | N | 0.212 | 0.194 | None | gnomAD-3.1.2 | 4.66442E-03 | None | None | None | None | I | None | 1.18158E-03 | 1.50563E-03 | 1.09649E-03 | 2.88018E-04 | 0 | None | 1.58133E-02 | 0 | 6.82132E-03 | 2.07039E-04 | 1.43267E-03 |
| K/E | rs72648984 |
0.424 | 0.216 | N | 0.212 | 0.194 | None | 1000 genomes | 1.59744E-03 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 8E-03 | None | None | None | 0 | None |
| K/E | rs72648984 |
0.424 | 0.216 | N | 0.212 | 0.194 | None | gnomAD-4.0.0 | 5.69265E-03 | None | None | None | None | I | None | 1.07931E-03 | 7.49825E-04 | None | 2.02716E-04 | 0 | None | 1.51193E-02 | 0 | 6.65662E-03 | 3.29374E-05 | 3.68082E-03 |
| K/N | rs373995644 |
0.325 | 0.056 | N | 0.151 | 0.103 | 0.0482279557977 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 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 | 0.3228 | likely_benign | 0.43 | ambiguous | -0.122 | Destabilizing | 0.008 | N | 0.136 | neutral | None | None | None | None | I |
| K/C | 0.764 | likely_pathogenic | 0.8461 | pathogenic | -0.093 | Destabilizing | 0.998 | D | 0.247 | neutral | None | None | None | None | I |
| K/D | 0.4452 | ambiguous | 0.5384 | ambiguous | 0.081 | Stabilizing | 0.549 | D | 0.266 | neutral | None | None | None | None | I |
| K/E | 0.161 | likely_benign | 0.1957 | benign | 0.135 | Stabilizing | 0.216 | N | 0.212 | neutral | N | 0.456313701 | None | None | I |
| K/F | 0.7957 | likely_pathogenic | 0.8735 | pathogenic | 0.008 | Stabilizing | 0.943 | D | 0.273 | neutral | None | None | None | None | I |
| K/G | 0.4678 | ambiguous | 0.5873 | pathogenic | -0.428 | Destabilizing | 0.008 | N | 0.142 | neutral | None | None | None | None | I |
| K/H | 0.2777 | likely_benign | 0.3194 | benign | -0.804 | Destabilizing | 0.946 | D | 0.263 | neutral | None | None | None | None | I |
| K/I | 0.4381 | ambiguous | 0.5624 | ambiguous | 0.636 | Stabilizing | 0.315 | N | 0.333 | neutral | N | 0.506059353 | None | None | I |
| K/L | 0.4664 | ambiguous | 0.59 | pathogenic | 0.636 | Stabilizing | 0.035 | N | 0.299 | neutral | None | None | None | None | I |
| K/M | 0.2697 | likely_benign | 0.3546 | ambiguous | 0.489 | Stabilizing | 0.834 | D | 0.267 | neutral | None | None | None | None | I |
| K/N | 0.3215 | likely_benign | 0.4114 | ambiguous | 0.078 | Stabilizing | 0.056 | N | 0.151 | neutral | N | 0.422198341 | None | None | I |
| K/P | 0.8752 | likely_pathogenic | 0.9376 | pathogenic | 0.414 | Stabilizing | 0.923 | D | 0.325 | neutral | None | None | None | None | I |
| K/Q | 0.1256 | likely_benign | 0.15 | benign | -0.054 | Destabilizing | 0.007 | N | 0.103 | neutral | N | 0.459431364 | None | None | I |
| K/R | 0.0832 | likely_benign | 0.0882 | benign | -0.292 | Destabilizing | 0.292 | N | 0.215 | neutral | N | 0.440768246 | None | None | I |
| K/S | 0.3535 | ambiguous | 0.4552 | ambiguous | -0.47 | Destabilizing | 0.088 | N | 0.095 | neutral | None | None | None | None | I |
| K/T | 0.1518 | likely_benign | 0.1996 | benign | -0.238 | Destabilizing | 0.018 | N | 0.166 | neutral | N | 0.462741028 | None | None | I |
| K/V | 0.3801 | ambiguous | 0.4876 | ambiguous | 0.414 | Stabilizing | 0.103 | N | 0.307 | neutral | None | None | None | None | I |
| K/W | 0.7878 | likely_pathogenic | 0.8492 | pathogenic | 0.062 | Stabilizing | 0.999 | D | 0.257 | neutral | None | None | None | None | I |
| K/Y | 0.6093 | likely_pathogenic | 0.7118 | pathogenic | 0.364 | Stabilizing | 0.856 | D | 0.265 | neutral | 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.