Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25787 | 77584;77585;77586 | chr2:178568773;178568772;178568771 | chr2:179433500;179433499;179433498 |
| N2AB | 24146 | 72661;72662;72663 | chr2:178568773;178568772;178568771 | chr2:179433500;179433499;179433498 |
| N2A | 23219 | 69880;69881;69882 | chr2:178568773;178568772;178568771 | chr2:179433500;179433499;179433498 |
| N2B | 16722 | 50389;50390;50391 | chr2:178568773;178568772;178568771 | chr2:179433500;179433499;179433498 |
| Novex-1 | 16847 | 50764;50765;50766 | chr2:178568773;178568772;178568771 | chr2:179433500;179433499;179433498 |
| Novex-2 | 16914 | 50965;50966;50967 | chr2:178568773;178568772;178568771 | chr2:179433500;179433499;179433498 |
| 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 | None | None | 0.981 | N | 0.439 | 0.193 | 0.655950369022 | gnomAD-4.0.0 | 6.84622E-07 | None | None | None | None | I | None | 0 | 2.23814E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs988340792  |
None | 0.203 | N | 0.343 | 0.118 | 0.230578612272 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/L | rs988340792 |
None | 0.203 | N | 0.343 | 0.118 | 0.230578612272 | gnomAD-4.0.0 | 5.58049E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.63157E-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 | 0.2643 | likely_benign | 0.2491 | benign | -0.536 | Destabilizing | 0.451 | N | 0.267 | neutral | N | 0.453811248 | None | None | I |
| V/C | 0.8336 | likely_pathogenic | 0.8266 | pathogenic | -0.855 | Destabilizing | 0.998 | D | 0.363 | neutral | None | None | None | None | I |
| V/D | 0.5422 | ambiguous | 0.5555 | ambiguous | -0.536 | Destabilizing | 0.907 | D | 0.459 | neutral | N | 0.44525048 | None | None | I |
| V/E | 0.454 | ambiguous | 0.4829 | ambiguous | -0.608 | Destabilizing | 0.302 | N | 0.28 | neutral | None | None | None | None | I |
| V/F | 0.225 | likely_benign | 0.2135 | benign | -0.665 | Destabilizing | 0.981 | D | 0.439 | neutral | N | 0.468958794 | None | None | I |
| V/G | 0.3188 | likely_benign | 0.3022 | benign | -0.658 | Destabilizing | 0.93 | D | 0.441 | neutral | N | 0.450637657 | None | None | I |
| V/H | 0.7384 | likely_pathogenic | 0.731 | pathogenic | -0.016 | Destabilizing | 0.048 | N | 0.449 | neutral | None | None | None | None | I |
| V/I | 0.0863 | likely_benign | 0.0891 | benign | -0.334 | Destabilizing | 0.556 | D | 0.315 | neutral | N | 0.503642635 | None | None | I |
| V/K | 0.5511 | ambiguous | 0.5651 | pathogenic | -0.545 | Destabilizing | 0.696 | D | 0.349 | neutral | None | None | None | None | I |
| V/L | 0.2305 | likely_benign | 0.2216 | benign | -0.334 | Destabilizing | 0.203 | N | 0.343 | neutral | N | 0.513723556 | None | None | I |
| V/M | 0.1738 | likely_benign | 0.1693 | benign | -0.698 | Destabilizing | 0.993 | D | 0.395 | neutral | None | None | None | None | I |
| V/N | 0.3871 | ambiguous | 0.4006 | ambiguous | -0.479 | Destabilizing | 0.405 | N | 0.512 | neutral | None | None | None | None | I |
| V/P | 0.7677 | likely_pathogenic | 0.7721 | pathogenic | -0.372 | Destabilizing | 0.829 | D | 0.529 | neutral | None | None | None | None | I |
| V/Q | 0.4638 | ambiguous | 0.4808 | ambiguous | -0.645 | Destabilizing | 0.051 | N | 0.332 | neutral | None | None | None | None | I |
| V/R | 0.5417 | ambiguous | 0.5505 | ambiguous | -0.06 | Destabilizing | 0.907 | D | 0.533 | neutral | None | None | None | None | I |
| V/S | 0.2983 | likely_benign | 0.2899 | benign | -0.795 | Destabilizing | 0.17 | N | 0.337 | neutral | None | None | None | None | I |
| V/T | 0.2743 | likely_benign | 0.2566 | benign | -0.767 | Destabilizing | 0.515 | D | 0.202 | neutral | None | None | None | None | I |
| V/W | 0.9072 | likely_pathogenic | 0.8996 | pathogenic | -0.739 | Destabilizing | 1.0 | D | 0.518 | neutral | None | None | None | None | I |
| V/Y | 0.6654 | likely_pathogenic | 0.6554 | pathogenic | -0.47 | Destabilizing | 0.972 | D | 0.451 | 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.