Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30670 | 92233;92234;92235 | chr2:178549714;178549713;178549712 | chr2:179414441;179414440;179414439 |
| N2AB | 29029 | 87310;87311;87312 | chr2:178549714;178549713;178549712 | chr2:179414441;179414440;179414439 |
| N2A | 28102 | 84529;84530;84531 | chr2:178549714;178549713;178549712 | chr2:179414441;179414440;179414439 |
| N2B | 21605 | 65038;65039;65040 | chr2:178549714;178549713;178549712 | chr2:179414441;179414440;179414439 |
| Novex-1 | 21730 | 65413;65414;65415 | chr2:178549714;178549713;178549712 | chr2:179414441;179414440;179414439 |
| Novex-2 | 21797 | 65614;65615;65616 | chr2:178549714;178549713;178549712 | chr2:179414441;179414440;179414439 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.927 | N | 0.525 | 0.151 | 0.317958651998 | gnomAD-4.0.0 | 1.08029E-05 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.05E-05 | 0 | 0 |
| I/S | None | None | 0.473 | N | 0.487 | 0.29 | 0.733736376693 | gnomAD-4.0.0 | 6.84238E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15937E-05 | 0 |
| I/T | rs369342933  |
-2.2 | 0.425 | N | 0.44 | 0.41 | None | gnomAD-2.1.1 | 2.46184E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.49004E-03 | None | 0 | None | 0 | 0 | 1.40292E-04 |
| I/T | rs369342933 |
-2.2 | 0.425 | N | 0.44 | 0.41 | None | gnomAD-3.1.2 | 1.11741E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 3.08285E-03 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs369342933 |
-2.2 | 0.425 | N | 0.44 | 0.41 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| I/T | rs369342933 |
-2.2 | 0.425 | N | 0.44 | 0.41 | None | gnomAD-4.0.0 | 1.25175E-04 | None | None | None | None | N | None | 1.33305E-05 | 1.66683E-05 | None | 0 | 3.90224E-03 | None | 0 | 0 | 1.69527E-06 | 0 | 3.68141E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3337 | likely_benign | 0.4048 | ambiguous | -1.83 | Destabilizing | 0.013 | N | 0.241 | neutral | None | None | None | None | N |
| I/C | 0.794 | likely_pathogenic | 0.8321 | pathogenic | -1.092 | Destabilizing | 0.981 | D | 0.527 | neutral | None | None | None | None | N |
| I/D | 0.9528 | likely_pathogenic | 0.9786 | pathogenic | -1.61 | Destabilizing | 0.981 | D | 0.577 | neutral | None | None | None | None | N |
| I/E | 0.8758 | likely_pathogenic | 0.929 | pathogenic | -1.492 | Destabilizing | 0.828 | D | 0.536 | neutral | None | None | None | None | N |
| I/F | 0.3471 | ambiguous | 0.5077 | ambiguous | -1.104 | Destabilizing | 0.927 | D | 0.501 | neutral | N | 0.45983593 | None | None | N |
| I/G | 0.8577 | likely_pathogenic | 0.9127 | pathogenic | -2.249 | Highly Destabilizing | 0.704 | D | 0.5 | neutral | None | None | None | None | N |
| I/H | 0.8641 | likely_pathogenic | 0.9299 | pathogenic | -1.41 | Destabilizing | 0.995 | D | 0.577 | neutral | None | None | None | None | N |
| I/K | 0.815 | likely_pathogenic | 0.8954 | pathogenic | -1.345 | Destabilizing | 0.828 | D | 0.543 | neutral | None | None | None | None | N |
| I/L | 0.1058 | likely_benign | 0.1238 | benign | -0.692 | Destabilizing | 0.065 | N | 0.305 | neutral | N | 0.376777403 | None | None | N |
| I/M | 0.106 | likely_benign | 0.1266 | benign | -0.572 | Destabilizing | 0.927 | D | 0.525 | neutral | N | 0.476461608 | None | None | N |
| I/N | 0.7265 | likely_pathogenic | 0.8299 | pathogenic | -1.467 | Destabilizing | 0.975 | D | 0.575 | neutral | N | 0.468761892 | None | None | N |
| I/P | 0.916 | likely_pathogenic | 0.9566 | pathogenic | -1.044 | Destabilizing | 0.981 | D | 0.579 | neutral | None | None | None | None | N |
| I/Q | 0.7776 | likely_pathogenic | 0.8524 | pathogenic | -1.481 | Destabilizing | 0.981 | D | 0.572 | neutral | None | None | None | None | N |
| I/R | 0.7558 | likely_pathogenic | 0.8552 | pathogenic | -0.883 | Destabilizing | 0.944 | D | 0.577 | neutral | None | None | None | None | N |
| I/S | 0.533 | ambiguous | 0.6362 | pathogenic | -2.098 | Highly Destabilizing | 0.473 | N | 0.487 | neutral | N | 0.484753017 | None | None | N |
| I/T | 0.195 | likely_benign | 0.2496 | benign | -1.845 | Destabilizing | 0.425 | N | 0.44 | neutral | N | 0.479808557 | None | None | N |
| I/V | 0.0808 | likely_benign | 0.0831 | benign | -1.044 | Destabilizing | 0.001 | N | 0.147 | neutral | N | 0.303415795 | None | None | N |
| I/W | 0.9141 | likely_pathogenic | 0.9597 | pathogenic | -1.322 | Destabilizing | 0.995 | D | 0.605 | neutral | None | None | None | None | N |
| I/Y | 0.8337 | likely_pathogenic | 0.9121 | pathogenic | -1.026 | Destabilizing | 0.981 | D | 0.543 | 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.