Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16017 | 48274;48275;48276 | chr2:178616840;178616839;178616838 | chr2:179481567;179481566;179481565 |
| N2AB | 14376 | 43351;43352;43353 | chr2:178616840;178616839;178616838 | chr2:179481567;179481566;179481565 |
| N2A | 13449 | 40570;40571;40572 | chr2:178616840;178616839;178616838 | chr2:179481567;179481566;179481565 |
| N2B | 6952 | 21079;21080;21081 | chr2:178616840;178616839;178616838 | chr2:179481567;179481566;179481565 |
| Novex-1 | 7077 | 21454;21455;21456 | chr2:178616840;178616839;178616838 | chr2:179481567;179481566;179481565 |
| Novex-2 | 7144 | 21655;21656;21657 | chr2:178616840;178616839;178616838 | chr2:179481567;179481566;179481565 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | None | None | 0.997 | N | 0.583 | 0.418 | 0.636530080196 | gnomAD-4.0.0 | 6.84615E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52704E-05 | None | 0 | 0 | 0 | 0 | 0 |
| Y/S | None | None | 0.891 | N | 0.582 | 0.324 | 0.68695168648 | gnomAD-4.0.0 | 6.84615E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99852E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.4414 | ambiguous | 0.4718 | ambiguous | -2.79 | Highly Destabilizing | 0.915 | D | 0.523 | neutral | None | None | None | None | N |
| Y/C | 0.1687 | likely_benign | 0.1623 | benign | -1.492 | Destabilizing | 0.997 | D | 0.583 | neutral | N | 0.506506575 | None | None | N |
| Y/D | 0.4833 | ambiguous | 0.5397 | ambiguous | -1.917 | Destabilizing | 0.989 | D | 0.602 | neutral | N | 0.499853165 | None | None | N |
| Y/E | 0.6878 | likely_pathogenic | 0.7269 | pathogenic | -1.82 | Destabilizing | 0.991 | D | 0.587 | neutral | None | None | None | None | N |
| Y/F | 0.0774 | likely_benign | 0.0749 | benign | -1.34 | Destabilizing | 0.002 | N | 0.144 | neutral | N | 0.424776643 | None | None | N |
| Y/G | 0.4416 | ambiguous | 0.4972 | ambiguous | -3.127 | Highly Destabilizing | 0.915 | D | 0.594 | neutral | None | None | None | None | N |
| Y/H | 0.1945 | likely_benign | 0.2059 | benign | -1.528 | Destabilizing | 0.989 | D | 0.501 | neutral | N | 0.500444872 | None | None | N |
| Y/I | 0.4884 | ambiguous | 0.5017 | ambiguous | -1.736 | Destabilizing | 0.728 | D | 0.477 | neutral | None | None | None | None | N |
| Y/K | 0.5604 | ambiguous | 0.6168 | pathogenic | -1.605 | Destabilizing | 0.991 | D | 0.587 | neutral | None | None | None | None | N |
| Y/L | 0.583 | likely_pathogenic | 0.6026 | pathogenic | -1.736 | Destabilizing | 0.525 | D | 0.454 | neutral | None | None | None | None | N |
| Y/M | 0.5752 | likely_pathogenic | 0.5799 | pathogenic | -1.378 | Destabilizing | 0.974 | D | 0.557 | neutral | None | None | None | None | N |
| Y/N | 0.25 | likely_benign | 0.2773 | benign | -1.963 | Destabilizing | 0.989 | D | 0.599 | neutral | N | 0.488662663 | None | None | N |
| Y/P | 0.9403 | likely_pathogenic | 0.9494 | pathogenic | -2.088 | Highly Destabilizing | 0.991 | D | 0.614 | neutral | None | None | None | None | N |
| Y/Q | 0.5149 | ambiguous | 0.5574 | ambiguous | -1.936 | Destabilizing | 0.991 | D | 0.575 | neutral | None | None | None | None | N |
| Y/R | 0.411 | ambiguous | 0.476 | ambiguous | -1.052 | Destabilizing | 0.991 | D | 0.604 | neutral | None | None | None | None | N |
| Y/S | 0.2089 | likely_benign | 0.2393 | benign | -2.486 | Highly Destabilizing | 0.891 | D | 0.582 | neutral | N | 0.471597986 | None | None | N |
| Y/T | 0.3764 | ambiguous | 0.4055 | ambiguous | -2.288 | Highly Destabilizing | 0.915 | D | 0.584 | neutral | None | None | None | None | N |
| Y/V | 0.3532 | ambiguous | 0.3657 | ambiguous | -2.088 | Highly Destabilizing | 0.842 | D | 0.453 | neutral | None | None | None | None | N |
| Y/W | 0.3553 | ambiguous | 0.3564 | ambiguous | -0.867 | Destabilizing | 0.991 | D | 0.491 | 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.