Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27528 | 82807;82808;82809 | chr2:178563550;178563549;178563548 | chr2:179428277;179428276;179428275 |
| N2AB | 25887 | 77884;77885;77886 | chr2:178563550;178563549;178563548 | chr2:179428277;179428276;179428275 |
| N2A | 24960 | 75103;75104;75105 | chr2:178563550;178563549;178563548 | chr2:179428277;179428276;179428275 |
| N2B | 18463 | 55612;55613;55614 | chr2:178563550;178563549;178563548 | chr2:179428277;179428276;179428275 |
| Novex-1 | 18588 | 55987;55988;55989 | chr2:178563550;178563549;178563548 | chr2:179428277;179428276;179428275 |
| Novex-2 | 18655 | 56188;56189;56190 | chr2:178563550;178563549;178563548 | chr2:179428277;179428276;179428275 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs765230578  |
0.185 | 0.994 | N | 0.658 | 0.211 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 8.88E-06 | 0 |
| R/Q | rs765230578 |
0.185 | 0.994 | N | 0.658 | 0.211 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs765230578 |
0.185 | 0.994 | N | 0.658 | 0.211 | None | gnomAD-4.0.0 | 1.61126E-05 | None | None | None | None | N | None | 1.33536E-05 | 1.66694E-05 | None | 0 | 2.22916E-05 | None | 0 | 0 | 1.78002E-05 | 1.09786E-05 | 1.60128E-05 |
| R/W | rs749852593 |
-0.222 | 1.0 | N | 0.635 | 0.325 | 0.387042434762 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 0 | 1.15895E-04 | None | 0 | 0 | None | 9.8E-05 | None | 0 | 8.88E-06 | 0 |
| R/W | rs749852593 |
-0.222 | 1.0 | N | 0.635 | 0.325 | 0.387042434762 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs749852593 |
-0.222 | 1.0 | N | 0.635 | 0.325 | 0.387042434762 | gnomAD-4.0.0 | 2.29299E-05 | None | None | None | None | N | None | 4.00641E-05 | 6.668E-05 | None | 0 | 0 | None | 0 | 0 | 1.52574E-05 | 1.31749E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.905 | likely_pathogenic | 0.9122 | pathogenic | -0.293 | Destabilizing | 0.845 | D | 0.562 | neutral | None | None | None | None | N |
| R/C | 0.3439 | ambiguous | 0.3389 | benign | -0.482 | Destabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | N |
| R/D | 0.9691 | likely_pathogenic | 0.9715 | pathogenic | 0.009 | Stabilizing | 0.975 | D | 0.643 | neutral | None | None | None | None | N |
| R/E | 0.8656 | likely_pathogenic | 0.8811 | pathogenic | 0.143 | Stabilizing | 0.845 | D | 0.553 | neutral | None | None | None | None | N |
| R/F | 0.8627 | likely_pathogenic | 0.8728 | pathogenic | -0.193 | Destabilizing | 0.996 | D | 0.661 | neutral | None | None | None | None | N |
| R/G | 0.8027 | likely_pathogenic | 0.8128 | pathogenic | -0.577 | Destabilizing | 0.954 | D | 0.579 | neutral | N | 0.483169617 | None | None | N |
| R/H | 0.1797 | likely_benign | 0.1775 | benign | -0.984 | Destabilizing | 0.987 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/I | 0.8079 | likely_pathogenic | 0.8213 | pathogenic | 0.454 | Stabilizing | 0.987 | D | 0.665 | neutral | None | None | None | None | N |
| R/K | 0.3776 | ambiguous | 0.3614 | ambiguous | -0.236 | Destabilizing | 0.033 | N | 0.399 | neutral | None | None | None | None | N |
| R/L | 0.6785 | likely_pathogenic | 0.6932 | pathogenic | 0.454 | Stabilizing | 0.954 | D | 0.579 | neutral | N | 0.490259961 | None | None | N |
| R/M | 0.8102 | likely_pathogenic | 0.817 | pathogenic | -0.167 | Destabilizing | 0.999 | D | 0.678 | prob.neutral | None | None | None | None | N |
| R/N | 0.9137 | likely_pathogenic | 0.9143 | pathogenic | -0.12 | Destabilizing | 0.975 | D | 0.656 | neutral | None | None | None | None | N |
| R/P | 0.9745 | likely_pathogenic | 0.9757 | pathogenic | 0.226 | Stabilizing | 0.993 | D | 0.665 | neutral | N | 0.519732382 | None | None | N |
| R/Q | 0.2555 | likely_benign | 0.2607 | benign | -0.124 | Destabilizing | 0.994 | D | 0.658 | neutral | N | 0.514825208 | None | None | N |
| R/S | 0.8794 | likely_pathogenic | 0.8873 | pathogenic | -0.641 | Destabilizing | 0.916 | D | 0.621 | neutral | None | None | None | None | N |
| R/T | 0.761 | likely_pathogenic | 0.7742 | pathogenic | -0.324 | Destabilizing | 0.975 | D | 0.656 | neutral | None | None | None | None | N |
| R/V | 0.8386 | likely_pathogenic | 0.8487 | pathogenic | 0.226 | Stabilizing | 0.975 | D | 0.658 | neutral | None | None | None | None | N |
| R/W | 0.3805 | ambiguous | 0.4161 | ambiguous | -0.08 | Destabilizing | 1.0 | D | 0.635 | neutral | N | 0.49102043 | None | None | N |
| R/Y | 0.6709 | likely_pathogenic | 0.6722 | pathogenic | 0.27 | Stabilizing | 0.996 | D | 0.673 | 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.