Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8207 | 24844;24845;24846 | chr2:178718487;178718486;178718485 | chr2:179583214;179583213;179583212 |
| N2AB | 7890 | 23893;23894;23895 | chr2:178718487;178718486;178718485 | chr2:179583214;179583213;179583212 |
| N2A | 6963 | 21112;21113;21114 | chr2:178718487;178718486;178718485 | chr2:179583214;179583213;179583212 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs751733811  |
-0.239 | 0.002 | N | 0.115 | 0.189 | 0.0806252709748 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 0 |
| D/E | rs751733811 |
-0.239 | 0.002 | N | 0.115 | 0.189 | 0.0806252709748 | gnomAD-4.0.0 | 2.73696E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.63736E-05 | 0 |
| D/N | rs756813056 |
-0.557 | None | N | 0.091 | 0.111 | 0.0920862733494 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | I | None | 0 | 1.74014E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 3.31565E-04 |
| D/N | rs756813056 |
-0.557 | None | N | 0.091 | 0.111 | 0.0920862733494 | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 0 | 5.23629E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs756813056 |
-0.557 | None | N | 0.091 | 0.111 | 0.0920862733494 | gnomAD-4.0.0 | 1.30143E-05 | None | None | None | None | I | None | 0 | 2.6672E-04 | None | 0 | 0 | None | 0 | 0 | 1.69527E-06 | 0 | 4.80384E-05 |
| D/Y | None | None | 0.741 | N | 0.445 | 0.268 | 0.339074221408 | gnomAD-4.0.0 | 1.36849E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79899E-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 | 0.2227 | likely_benign | 0.1961 | benign | -0.561 | Destabilizing | 0.052 | N | 0.361 | neutral | N | 0.485729468 | None | None | I |
| D/C | 0.6872 | likely_pathogenic | 0.5901 | pathogenic | -0.371 | Destabilizing | 0.935 | D | 0.461 | neutral | None | None | None | None | I |
| D/E | 0.2027 | likely_benign | 0.178 | benign | -0.487 | Destabilizing | 0.002 | N | 0.115 | neutral | N | 0.467496628 | None | None | I |
| D/F | 0.7457 | likely_pathogenic | 0.6773 | pathogenic | 0.114 | Stabilizing | 0.791 | D | 0.435 | neutral | None | None | None | None | I |
| D/G | 0.1046 | likely_benign | 0.0957 | benign | -0.919 | Destabilizing | 0.027 | N | 0.297 | neutral | N | 0.455922831 | None | None | I |
| D/H | 0.2942 | likely_benign | 0.256 | benign | -0.032 | Destabilizing | 0.317 | N | 0.393 | neutral | N | 0.506809464 | None | None | I |
| D/I | 0.6873 | likely_pathogenic | 0.607 | pathogenic | 0.393 | Stabilizing | 0.555 | D | 0.447 | neutral | None | None | None | None | I |
| D/K | 0.3299 | likely_benign | 0.29 | benign | -0.477 | Destabilizing | 0.035 | N | 0.307 | neutral | None | None | None | None | I |
| D/L | 0.5688 | likely_pathogenic | 0.4805 | ambiguous | 0.393 | Stabilizing | 0.149 | N | 0.412 | neutral | None | None | None | None | I |
| D/M | 0.7141 | likely_pathogenic | 0.6499 | pathogenic | 0.682 | Stabilizing | 0.935 | D | 0.42 | neutral | None | None | None | None | I |
| D/N | 0.0637 | likely_benign | 0.0654 | benign | -0.987 | Destabilizing | None | N | 0.091 | neutral | N | 0.438180074 | None | None | I |
| D/P | 0.862 | likely_pathogenic | 0.8513 | pathogenic | 0.099 | Stabilizing | 0.555 | D | 0.372 | neutral | None | None | None | None | I |
| D/Q | 0.3429 | ambiguous | 0.3031 | benign | -0.811 | Destabilizing | 0.149 | N | 0.306 | neutral | None | None | None | None | I |
| D/R | 0.3641 | ambiguous | 0.3248 | benign | -0.152 | Destabilizing | 0.149 | N | 0.395 | neutral | None | None | None | None | I |
| D/S | 0.1295 | likely_benign | 0.1204 | benign | -1.238 | Destabilizing | 0.035 | N | 0.283 | neutral | None | None | None | None | I |
| D/T | 0.3859 | ambiguous | 0.3396 | benign | -0.938 | Destabilizing | 0.081 | N | 0.31 | neutral | None | None | None | None | I |
| D/V | 0.497 | ambiguous | 0.4241 | ambiguous | 0.099 | Stabilizing | 0.211 | N | 0.421 | neutral | N | 0.507062953 | None | None | I |
| D/W | 0.8789 | likely_pathogenic | 0.8455 | pathogenic | 0.364 | Stabilizing | 0.935 | D | 0.523 | neutral | None | None | None | None | I |
| D/Y | 0.2708 | likely_benign | 0.2268 | benign | 0.36 | Stabilizing | 0.741 | D | 0.445 | neutral | N | 0.507062953 | 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.