Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14270 | 43033;43034;43035 | chr2:178633551;178633550;178633549 | chr2:179498278;179498277;179498276 |
| N2AB | 12629 | 38110;38111;38112 | chr2:178633551;178633550;178633549 | chr2:179498278;179498277;179498276 |
| N2A | 11702 | 35329;35330;35331 | chr2:178633551;178633550;178633549 | chr2:179498278;179498277;179498276 |
| N2B | 5205 | 15838;15839;15840 | chr2:178633551;178633550;178633549 | chr2:179498278;179498277;179498276 |
| Novex-1 | 5330 | 16213;16214;16215 | chr2:178633551;178633550;178633549 | chr2:179498278;179498277;179498276 |
| Novex-2 | 5397 | 16414;16415;16416 | chr2:178633551;178633550;178633549 | chr2:179498278;179498277;179498276 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | rs1187293520  |
-0.627 | 0.093 | N | 0.417 | 0.038 | 0.405012372841 | 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 |
| V/F | rs1187293520 |
-0.627 | 0.093 | N | 0.417 | 0.038 | 0.405012372841 | gnomAD-4.0.0 | 1.36875E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31879E-05 | 0 |
| V/I | None | None | None | N | 0.172 | 0.058 | 0.259761712551 | gnomAD-4.0.0 | 6.84376E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9959E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0803 | likely_benign | 0.0846 | benign | -0.556 | Destabilizing | 0.005 | N | 0.169 | neutral | N | 0.492765071 | None | None | N |
| V/C | 0.5099 | ambiguous | 0.5259 | ambiguous | -0.844 | Destabilizing | 0.356 | N | 0.339 | neutral | None | None | None | None | N |
| V/D | 0.1844 | likely_benign | 0.1577 | benign | -0.353 | Destabilizing | 0.029 | N | 0.444 | neutral | N | 0.487090492 | None | None | N |
| V/E | 0.1423 | likely_benign | 0.1202 | benign | -0.415 | Destabilizing | None | N | 0.195 | neutral | None | None | None | None | N |
| V/F | 0.117 | likely_benign | 0.1014 | benign | -0.599 | Destabilizing | 0.093 | N | 0.417 | neutral | N | 0.488521823 | None | None | N |
| V/G | 0.1074 | likely_benign | 0.1068 | benign | -0.711 | Destabilizing | 0.024 | N | 0.413 | neutral | N | 0.494356381 | None | None | N |
| V/H | 0.2263 | likely_benign | 0.2616 | benign | -0.101 | Destabilizing | 0.356 | N | 0.42 | neutral | None | None | None | None | N |
| V/I | 0.0657 | likely_benign | 0.0652 | benign | -0.268 | Destabilizing | None | N | 0.172 | neutral | N | 0.468986144 | None | None | N |
| V/K | 0.1002 | likely_benign | 0.1154 | benign | -0.559 | Destabilizing | None | N | 0.158 | neutral | None | None | None | None | N |
| V/L | 0.0879 | likely_benign | 0.0812 | benign | -0.268 | Destabilizing | None | N | 0.148 | neutral | N | 0.488444825 | None | None | N |
| V/M | 0.0964 | likely_benign | 0.0915 | benign | -0.599 | Destabilizing | 0.12 | N | 0.257 | neutral | None | None | None | None | N |
| V/N | 0.0994 | likely_benign | 0.1038 | benign | -0.481 | Destabilizing | 0.072 | N | 0.475 | neutral | None | None | None | None | N |
| V/P | 0.1795 | likely_benign | 0.2093 | benign | -0.332 | Destabilizing | 0.136 | N | 0.469 | neutral | None | None | None | None | N |
| V/Q | 0.1175 | likely_benign | 0.1285 | benign | -0.619 | Destabilizing | 0.038 | N | 0.437 | neutral | None | None | None | None | N |
| V/R | 0.128 | likely_benign | 0.1394 | benign | -0.105 | Destabilizing | None | N | 0.246 | neutral | None | None | None | None | N |
| V/S | 0.0786 | likely_benign | 0.0875 | benign | -0.851 | Destabilizing | 0.016 | N | 0.322 | neutral | None | None | None | None | N |
| V/T | 0.0717 | likely_benign | 0.0788 | benign | -0.803 | Destabilizing | None | N | 0.142 | neutral | None | None | None | None | N |
| V/W | 0.639 | likely_pathogenic | 0.5957 | pathogenic | -0.696 | Destabilizing | 0.864 | D | 0.419 | neutral | None | None | None | None | N |
| V/Y | 0.3121 | likely_benign | 0.3013 | benign | -0.415 | Destabilizing | 0.356 | N | 0.403 | 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.