Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21202 | 63829;63830;63831 | chr2:178587705;178587704;178587703 | chr2:179452432;179452431;179452430 |
| N2AB | 19561 | 58906;58907;58908 | chr2:178587705;178587704;178587703 | chr2:179452432;179452431;179452430 |
| N2A | 18634 | 56125;56126;56127 | chr2:178587705;178587704;178587703 | chr2:179452432;179452431;179452430 |
| N2B | 12137 | 36634;36635;36636 | chr2:178587705;178587704;178587703 | chr2:179452432;179452431;179452430 |
| Novex-1 | 12262 | 37009;37010;37011 | chr2:178587705;178587704;178587703 | chr2:179452432;179452431;179452430 |
| Novex-2 | 12329 | 37210;37211;37212 | chr2:178587705;178587704;178587703 | chr2:179452432;179452431;179452430 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs752725604  |
-0.077 | 1.0 | D | 0.661 | 0.783 | 0.600640161457 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/S | rs752725604 |
-0.077 | 1.0 | D | 0.661 | 0.783 | 0.600640161457 | gnomAD-4.0.0 | 2.73823E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69925E-06 | 1.15988E-05 | 0 |
| P/T | None | None | 1.0 | D | 0.657 | 0.757 | 0.641703553165 | gnomAD-4.0.0 | 6.84558E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9975E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.8976 | likely_pathogenic | 0.8947 | pathogenic | -0.571 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | D | 0.584826837 | None | None | I |
| P/C | 0.9904 | likely_pathogenic | 0.9909 | pathogenic | -0.5 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| P/D | 0.9852 | likely_pathogenic | 0.9845 | pathogenic | -0.631 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| P/E | 0.9768 | likely_pathogenic | 0.973 | pathogenic | -0.757 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| P/F | 0.9954 | likely_pathogenic | 0.995 | pathogenic | -0.863 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| P/G | 0.9733 | likely_pathogenic | 0.9726 | pathogenic | -0.697 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| P/H | 0.9734 | likely_pathogenic | 0.973 | pathogenic | -0.354 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | I |
| P/I | 0.9638 | likely_pathogenic | 0.9597 | pathogenic | -0.388 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | I |
| P/K | 0.9785 | likely_pathogenic | 0.9765 | pathogenic | -0.584 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| P/L | 0.8967 | likely_pathogenic | 0.8901 | pathogenic | -0.388 | Destabilizing | 1.0 | D | 0.66 | neutral | D | 0.612242761 | None | None | I |
| P/M | 0.9732 | likely_pathogenic | 0.973 | pathogenic | -0.342 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| P/N | 0.9806 | likely_pathogenic | 0.9806 | pathogenic | -0.22 | Destabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | I |
| P/Q | 0.9689 | likely_pathogenic | 0.9667 | pathogenic | -0.511 | Destabilizing | 1.0 | D | 0.665 | neutral | D | 0.584826837 | None | None | I |
| P/R | 0.9603 | likely_pathogenic | 0.9561 | pathogenic | -0.012 | Destabilizing | 1.0 | D | 0.666 | neutral | D | 0.653396625 | None | None | I |
| P/S | 0.9655 | likely_pathogenic | 0.9648 | pathogenic | -0.507 | Destabilizing | 1.0 | D | 0.661 | neutral | D | 0.572963553 | None | None | I |
| P/T | 0.9108 | likely_pathogenic | 0.9041 | pathogenic | -0.545 | Destabilizing | 1.0 | D | 0.657 | neutral | D | 0.653396625 | None | None | I |
| P/V | 0.9278 | likely_pathogenic | 0.9208 | pathogenic | -0.415 | Destabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | I |
| P/W | 0.9977 | likely_pathogenic | 0.9977 | pathogenic | -0.95 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| P/Y | 0.9924 | likely_pathogenic | 0.9922 | pathogenic | -0.662 | Destabilizing | 1.0 | D | 0.697 | prob.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.