Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1306 | 4141;4142;4143 | chr2:178779276;178779275;178779274 | chr2:179644003;179644002;179644001 |
| N2AB | 1306 | 4141;4142;4143 | chr2:178779276;178779275;178779274 | chr2:179644003;179644002;179644001 |
| N2A | 1306 | 4141;4142;4143 | chr2:178779276;178779275;178779274 | chr2:179644003;179644002;179644001 |
| N2B | 1260 | 4003;4004;4005 | chr2:178779276;178779275;178779274 | chr2:179644003;179644002;179644001 |
| Novex-1 | 1260 | 4003;4004;4005 | chr2:178779276;178779275;178779274 | chr2:179644003;179644002;179644001 |
| Novex-2 | 1260 | 4003;4004;4005 | chr2:178779276;178779275;178779274 | chr2:179644003;179644002;179644001 |
| Novex-3 | 1306 | 4141;4142;4143 | chr2:178779276;178779275;178779274 | chr2:179644003;179644002;179644001 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs2092551024  |
None | 0.351 | N | 0.231 | 0.183 | 0.301789629655 | gnomAD-4.0.0 | 1.20045E-06 | None | None | None | None | I | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/K | rs1410771859 |
0.523 | 0.002 | N | 0.135 | 0.233 | 0.358340041657 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| M/K | rs1410771859 |
0.523 | 0.002 | N | 0.135 | 0.233 | 0.358340041657 | gnomAD-4.0.0 | 1.59108E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85732E-06 | 0 | 0 |
| M/L | rs1480447156 |
0.103 | 0.047 | N | 0.228 | 0.238 | 0.386234084001 | gnomAD-2.1.1 | 4E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| M/L | rs1480447156 |
0.103 | 0.047 | N | 0.228 | 0.238 | 0.386234084001 | gnomAD-4.0.0 | 1.59106E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85724E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4571 | ambiguous | 0.5761 | pathogenic | -0.572 | Destabilizing | 0.129 | N | 0.291 | neutral | None | None | None | None | I |
| M/C | 0.8607 | likely_pathogenic | 0.8875 | pathogenic | -0.711 | Destabilizing | 0.983 | D | 0.303 | neutral | None | None | None | None | I |
| M/D | 0.8606 | likely_pathogenic | 0.9024 | pathogenic | 0.505 | Stabilizing | 0.418 | N | 0.441 | neutral | None | None | None | None | I |
| M/E | 0.5769 | likely_pathogenic | 0.6637 | pathogenic | 0.496 | Stabilizing | 0.264 | N | 0.345 | neutral | None | None | None | None | I |
| M/F | 0.3838 | ambiguous | 0.4363 | ambiguous | 0.077 | Stabilizing | 0.836 | D | 0.3 | neutral | None | None | None | None | I |
| M/G | 0.7418 | likely_pathogenic | 0.8273 | pathogenic | -0.805 | Destabilizing | 0.264 | N | 0.391 | neutral | None | None | None | None | I |
| M/H | 0.6242 | likely_pathogenic | 0.6989 | pathogenic | 0.126 | Stabilizing | 0.836 | D | 0.35 | neutral | None | None | None | None | I |
| M/I | 0.5532 | ambiguous | 0.6419 | pathogenic | -0.032 | Destabilizing | 0.351 | N | 0.231 | neutral | N | 0.447225213 | None | None | I |
| M/K | 0.361 | ambiguous | 0.4448 | ambiguous | 0.31 | Stabilizing | 0.002 | N | 0.135 | neutral | N | 0.414754053 | None | None | I |
| M/L | 0.2001 | likely_benign | 0.2301 | benign | -0.032 | Destabilizing | 0.047 | N | 0.228 | neutral | N | 0.44491048 | None | None | I |
| M/N | 0.5757 | likely_pathogenic | 0.6747 | pathogenic | 0.348 | Stabilizing | 0.418 | N | 0.376 | neutral | None | None | None | None | I |
| M/P | 0.9846 | likely_pathogenic | 0.9907 | pathogenic | -0.182 | Destabilizing | 0.593 | D | 0.418 | neutral | None | None | None | None | I |
| M/Q | 0.2952 | likely_benign | 0.3717 | ambiguous | 0.275 | Stabilizing | 0.264 | N | 0.287 | neutral | None | None | None | None | I |
| M/R | 0.3625 | ambiguous | 0.44 | ambiguous | 0.738 | Stabilizing | 0.213 | N | 0.297 | neutral | N | 0.4298203 | None | None | I |
| M/S | 0.4665 | ambiguous | 0.5929 | pathogenic | -0.201 | Destabilizing | 0.01 | N | 0.129 | neutral | None | None | None | None | I |
| M/T | 0.3071 | likely_benign | 0.425 | ambiguous | -0.094 | Destabilizing | 0.003 | N | 0.133 | neutral | N | 0.390231299 | None | None | I |
| M/V | 0.1732 | likely_benign | 0.2129 | benign | -0.182 | Destabilizing | 0.101 | N | 0.314 | neutral | N | 0.445286443 | None | None | I |
| M/W | 0.7286 | likely_pathogenic | 0.7783 | pathogenic | 0.081 | Stabilizing | 0.983 | D | 0.329 | neutral | None | None | None | None | I |
| M/Y | 0.6343 | likely_pathogenic | 0.6836 | pathogenic | 0.2 | Stabilizing | 0.94 | D | 0.322 | 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.