Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30975 | 93148;93149;93150 | chr2:178548703;178548702;178548701 | chr2:179413430;179413429;179413428 |
| N2AB | 29334 | 88225;88226;88227 | chr2:178548703;178548702;178548701 | chr2:179413430;179413429;179413428 |
| N2A | 28407 | 85444;85445;85446 | chr2:178548703;178548702;178548701 | chr2:179413430;179413429;179413428 |
| N2B | 21910 | 65953;65954;65955 | chr2:178548703;178548702;178548701 | chr2:179413430;179413429;179413428 |
| Novex-1 | 22035 | 66328;66329;66330 | chr2:178548703;178548702;178548701 | chr2:179413430;179413429;179413428 |
| Novex-2 | 22102 | 66529;66530;66531 | chr2:178548703;178548702;178548701 | chr2:179413430;179413429;179413428 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | None | None | 0.999 | N | 0.623 | 0.496 | 0.659988389567 | gnomAD-4.0.0 | 6.84192E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99455E-07 | 0 | 0 |
| T/K | rs761971680  |
-0.159 | 0.999 | D | 0.568 | 0.472 | None | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 6.46E-05 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/K | rs761971680 |
-0.159 | 0.999 | D | 0.568 | 0.472 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 2.41E-05 | 2.61883E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07039E-04 | 0 |
| T/K | rs761971680 |
-0.159 | 0.999 | D | 0.568 | 0.472 | None | gnomAD-4.0.0 | 8.05575E-06 | None | None | None | None | N | None | 1.33479E-05 | 1.00017E-04 | None | 0 | 0 | None | 0 | 0 | 4.23798E-06 | 1.09784E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1751 | likely_benign | 0.1744 | benign | -0.875 | Destabilizing | 0.767 | D | 0.275 | neutral | N | 0.486226215 | None | None | N |
| T/C | 0.7598 | likely_pathogenic | 0.7309 | pathogenic | -0.31 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| T/D | 0.6011 | likely_pathogenic | 0.5772 | pathogenic | 0.304 | Stabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | N |
| T/E | 0.6462 | likely_pathogenic | 0.643 | pathogenic | 0.313 | Stabilizing | 1.0 | D | 0.574 | neutral | None | None | None | None | N |
| T/F | 0.7542 | likely_pathogenic | 0.741 | pathogenic | -1.007 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| T/G | 0.3407 | ambiguous | 0.3198 | benign | -1.124 | Destabilizing | 0.997 | D | 0.527 | neutral | None | None | None | None | N |
| T/H | 0.6363 | likely_pathogenic | 0.6098 | pathogenic | -1.27 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| T/I | 0.6935 | likely_pathogenic | 0.686 | pathogenic | -0.3 | Destabilizing | 0.999 | D | 0.623 | neutral | N | 0.490291593 | None | None | N |
| T/K | 0.5017 | ambiguous | 0.4878 | ambiguous | -0.441 | Destabilizing | 0.999 | D | 0.568 | neutral | D | 0.531517962 | None | None | N |
| T/L | 0.3398 | likely_benign | 0.3304 | benign | -0.3 | Destabilizing | 0.997 | D | 0.478 | neutral | None | None | None | None | N |
| T/M | 0.2306 | likely_benign | 0.2291 | benign | -0.071 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| T/N | 0.2702 | likely_benign | 0.2447 | benign | -0.39 | Destabilizing | 1.0 | D | 0.595 | neutral | None | None | None | None | N |
| T/P | 0.7151 | likely_pathogenic | 0.6843 | pathogenic | -0.46 | Destabilizing | 0.999 | D | 0.624 | neutral | N | 0.511687531 | None | None | N |
| T/Q | 0.5427 | ambiguous | 0.5262 | ambiguous | -0.48 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| T/R | 0.4395 | ambiguous | 0.431 | ambiguous | -0.257 | Destabilizing | 0.999 | D | 0.609 | neutral | D | 0.526170857 | None | None | N |
| T/S | 0.1513 | likely_benign | 0.1403 | benign | -0.741 | Destabilizing | 0.992 | D | 0.388 | neutral | N | 0.512009481 | None | None | N |
| T/V | 0.4613 | ambiguous | 0.4641 | ambiguous | -0.46 | Destabilizing | 0.997 | D | 0.419 | neutral | None | None | None | None | N |
| T/W | 0.9126 | likely_pathogenic | 0.9035 | pathogenic | -0.95 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/Y | 0.7822 | likely_pathogenic | 0.7603 | pathogenic | -0.708 | Destabilizing | 1.0 | D | 0.698 | prob.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.