Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33365 | 100318;100319;100320 | chr2:178537016;178537015;178537014 | chr2:179401743;179401742;179401741 |
| N2AB | 31724 | 95395;95396;95397 | chr2:178537016;178537015;178537014 | chr2:179401743;179401742;179401741 |
| N2A | 30797 | 92614;92615;92616 | chr2:178537016;178537015;178537014 | chr2:179401743;179401742;179401741 |
| N2B | 24300 | 73123;73124;73125 | chr2:178537016;178537015;178537014 | chr2:179401743;179401742;179401741 |
| Novex-1 | 24425 | 73498;73499;73500 | chr2:178537016;178537015;178537014 | chr2:179401743;179401742;179401741 |
| Novex-2 | 24492 | 73699;73700;73701 | chr2:178537016;178537015;178537014 | chr2:179401743;179401742;179401741 |
| 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 | rs55742743  |
-0.838 | 1.0 | N | 0.783 | 0.485 | None | gnomAD-2.1.1 | 1.24199E-02 | None | None | None | None | N | None | 3.32005E-03 | 6.19494E-03 | None | 2.22244E-02 | 1.02934E-04 | None | 6.7412E-03 | None | 2.72349E-03 | 2.01439E-02 | 1.32619E-02 |
| R/Q | rs55742743 |
-0.838 | 1.0 | N | 0.783 | 0.485 | None | gnomAD-3.1.2 | 1.26186E-02 | None | None | None | None | N | None | 4.07878E-03 | 8.11731E-03 | 1.75439E-02 | 1.98847E-02 | 0 | None | 4.05202E-03 | 9.49367E-03 | 2.10495E-02 | 8.49213E-03 | 1.09943E-02 |
| R/Q | rs55742743 |
-0.838 | 1.0 | N | 0.783 | 0.485 | None | 1000 genomes | 4.79233E-03 | None | None | None | None | N | None | 0 | 4.3E-03 | None | None | 0 | 1.79E-02 | None | None | None | 3.1E-03 | None |
| R/Q | rs55742743 |
-0.838 | 1.0 | N | 0.783 | 0.485 | None | gnomAD-4.0.0 | 1.8557E-02 | None | None | None | None | N | None | 3.73333E-03 | 7.10592E-03 | None | 2.18391E-02 | 2.23095E-05 | None | 3.54876E-03 | 6.60066E-03 | 2.24475E-02 | 7.67455E-03 | 1.80127E-02 |
| R/W | rs543226487 |
-0.581 | 1.0 | D | 0.769 | 0.636 | 0.687425107779 | gnomAD-2.1.1 | 1.08E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 1.57E-05 | 0 |
| R/W | rs543226487 |
-0.581 | 1.0 | D | 0.769 | 0.636 | 0.687425107779 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/W | rs543226487 |
-0.581 | 1.0 | D | 0.769 | 0.636 | 0.687425107779 | gnomAD-4.0.0 | 3.71948E-06 | None | None | None | None | N | None | 1.3354E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54329E-06 | 1.09965E-05 | 1.60179E-05 |
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 | 0.9893 | likely_pathogenic | 0.9844 | pathogenic | -1.616 | Destabilizing | 0.999 | D | 0.625 | neutral | None | None | None | None | N |
| R/C | 0.7812 | likely_pathogenic | 0.7289 | pathogenic | -1.586 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| R/D | 0.9991 | likely_pathogenic | 0.9985 | pathogenic | -0.848 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| R/E | 0.9865 | likely_pathogenic | 0.979 | pathogenic | -0.641 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| R/F | 0.996 | likely_pathogenic | 0.9938 | pathogenic | -0.802 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| R/G | 0.9855 | likely_pathogenic | 0.9784 | pathogenic | -1.957 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | D | 0.541146594 | None | None | N |
| R/H | 0.6954 | likely_pathogenic | 0.6225 | pathogenic | -1.884 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| R/I | 0.9804 | likely_pathogenic | 0.9695 | pathogenic | -0.639 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| R/K | 0.5439 | ambiguous | 0.4787 | ambiguous | -1.167 | Destabilizing | 0.998 | D | 0.645 | neutral | None | None | None | None | N |
| R/L | 0.9651 | likely_pathogenic | 0.9455 | pathogenic | -0.639 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | D | 0.523295828 | None | None | N |
| R/M | 0.9864 | likely_pathogenic | 0.9788 | pathogenic | -1.18 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| R/N | 0.9963 | likely_pathogenic | 0.9942 | pathogenic | -1.143 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| R/P | 0.9997 | likely_pathogenic | 0.9994 | pathogenic | -0.953 | Destabilizing | 1.0 | D | 0.795 | deleterious | D | 0.553009878 | None | None | N |
| R/Q | 0.657 | likely_pathogenic | 0.4234 | ambiguous | -0.954 | Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.502087247 | None | None | N |
| R/S | 0.9927 | likely_pathogenic | 0.9886 | pathogenic | -1.917 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| R/T | 0.9893 | likely_pathogenic | 0.9823 | pathogenic | -1.509 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/V | 0.9845 | likely_pathogenic | 0.9774 | pathogenic | -0.953 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| R/W | 0.9505 | likely_pathogenic | 0.9016 | pathogenic | -0.436 | Destabilizing | 1.0 | D | 0.769 | deleterious | D | 0.552756389 | None | None | N |
| R/Y | 0.9887 | likely_pathogenic | 0.9826 | pathogenic | -0.249 | Destabilizing | 1.0 | D | 0.832 | deleterious | 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.