Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15518 | 46777;46778;46779 | chr2:178619765;178619764;178619763 | chr2:179484492;179484491;179484490 |
| N2AB | 13877 | 41854;41855;41856 | chr2:178619765;178619764;178619763 | chr2:179484492;179484491;179484490 |
| N2A | 12950 | 39073;39074;39075 | chr2:178619765;178619764;178619763 | chr2:179484492;179484491;179484490 |
| N2B | 6453 | 19582;19583;19584 | chr2:178619765;178619764;178619763 | chr2:179484492;179484491;179484490 |
| Novex-1 | 6578 | 19957;19958;19959 | chr2:178619765;178619764;178619763 | chr2:179484492;179484491;179484490 |
| Novex-2 | 6645 | 20158;20159;20160 | chr2:178619765;178619764;178619763 | chr2:179484492;179484491;179484490 |
| 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/A | None | None | 0.01 | N | 0.217 | 0.133 | 0.583928190899 | gnomAD-4.0.0 | 1.59394E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86418E-06 | 0 | 0 |
| V/F | None | None | 0.171 | N | 0.431 | 0.069 | 0.584551062954 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31251E-06 | 0 | 0 |
| V/I | None | None | None | N | 0.135 | 0.099 | 0.356484672536 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31251E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.152 | likely_benign | 0.1563 | benign | -0.783 | Destabilizing | 0.01 | N | 0.217 | neutral | N | 0.451968271 | None | None | N |
| V/C | 0.7127 | likely_pathogenic | 0.7691 | pathogenic | -0.596 | Destabilizing | 0.628 | D | 0.373 | neutral | None | None | None | None | N |
| V/D | 0.4416 | ambiguous | 0.4473 | ambiguous | -0.718 | Destabilizing | 0.106 | N | 0.411 | neutral | N | 0.441132102 | None | None | N |
| V/E | 0.3091 | likely_benign | 0.2957 | benign | -0.807 | Destabilizing | 0.136 | N | 0.411 | neutral | None | None | None | None | N |
| V/F | 0.1961 | likely_benign | 0.1914 | benign | -0.825 | Destabilizing | 0.171 | N | 0.431 | neutral | N | 0.486348146 | None | None | N |
| V/G | 0.3074 | likely_benign | 0.313 | benign | -0.97 | Destabilizing | 0.106 | N | 0.379 | neutral | N | 0.485752372 | None | None | N |
| V/H | 0.4997 | ambiguous | 0.5031 | ambiguous | -0.548 | Destabilizing | 0.864 | D | 0.379 | neutral | None | None | None | None | N |
| V/I | 0.0643 | likely_benign | 0.0662 | benign | -0.416 | Destabilizing | None | N | 0.135 | neutral | N | 0.443383317 | None | None | N |
| V/K | 0.2539 | likely_benign | 0.2516 | benign | -0.792 | Destabilizing | 0.072 | N | 0.411 | neutral | None | None | None | None | N |
| V/L | 0.1369 | likely_benign | 0.1374 | benign | -0.416 | Destabilizing | None | N | 0.143 | neutral | N | 0.402515489 | None | None | N |
| V/M | 0.1177 | likely_benign | 0.1258 | benign | -0.378 | Destabilizing | 0.214 | N | 0.361 | neutral | None | None | None | None | N |
| V/N | 0.2431 | likely_benign | 0.2619 | benign | -0.475 | Destabilizing | 0.356 | N | 0.432 | neutral | None | None | None | None | N |
| V/P | 0.2445 | likely_benign | 0.2463 | benign | -0.503 | Destabilizing | None | N | 0.231 | neutral | None | None | None | None | N |
| V/Q | 0.2891 | likely_benign | 0.2802 | benign | -0.721 | Destabilizing | 0.628 | D | 0.397 | neutral | None | None | None | None | N |
| V/R | 0.2528 | likely_benign | 0.2325 | benign | -0.218 | Destabilizing | 0.356 | N | 0.427 | neutral | None | None | None | None | N |
| V/S | 0.2387 | likely_benign | 0.2501 | benign | -0.825 | Destabilizing | 0.038 | N | 0.389 | neutral | None | None | None | None | N |
| V/T | 0.1369 | likely_benign | 0.1521 | benign | -0.819 | Destabilizing | None | N | 0.13 | neutral | None | None | None | None | N |
| V/W | 0.7596 | likely_pathogenic | 0.765 | pathogenic | -0.942 | Destabilizing | 0.864 | D | 0.411 | neutral | None | None | None | None | N |
| V/Y | 0.5349 | ambiguous | 0.5519 | ambiguous | -0.663 | Destabilizing | 0.356 | N | 0.419 | 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.