Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32971 | 99136;99137;99138 | chr2:178539024;178539023;178539022 | chr2:179403751;179403750;179403749 |
| N2AB | 31330 | 94213;94214;94215 | chr2:178539024;178539023;178539022 | chr2:179403751;179403750;179403749 |
| N2A | 30403 | 91432;91433;91434 | chr2:178539024;178539023;178539022 | chr2:179403751;179403750;179403749 |
| N2B | 23906 | 71941;71942;71943 | chr2:178539024;178539023;178539022 | chr2:179403751;179403750;179403749 |
| Novex-1 | 24031 | 72316;72317;72318 | chr2:178539024;178539023;178539022 | chr2:179403751;179403750;179403749 |
| Novex-2 | 24098 | 72517;72518;72519 | chr2:178539024;178539023;178539022 | chr2:179403751;179403750;179403749 |
| 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/C | rs765870426  |
-1.568 | 1.0 | D | 0.789 | 0.467 | 0.73073095 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/C | rs765870426 |
-1.568 | 1.0 | D | 0.789 | 0.467 | 0.73073095 | gnomAD-4.0.0 | 5.47395E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.4976E-06 | 1.15942E-05 | 3.31378E-05 |
| R/H | rs4894028 |
-2.268 | 1.0 | D | 0.818 | 0.435 | None | 1000 genomes | 7.6877E-02 | None | None | None | None | N | None | 1.13E-02 | 1.484E-01 | None | None | 2.48E-02 | 4.77E-02 | None | None | None | 1.984E-01 | None |
| R/H | rs4894028 |
-2.268 | 1.0 | D | 0.818 | 0.435 | None | gnomAD-2.1.1 | 6.94271E-02 | None | None | None | None | N | None | 1.24421E-02 | 1.93579E-01 | None | 2.96905E-02 | 2.77208E-02 | None | 1.8096E-01 | None | 5.70983E-02 | 3.18791E-02 | 5.73517E-02 |
| R/H | rs4894028 |
-2.268 | 1.0 | D | 0.818 | 0.435 | None | gnomAD-3.1.2 | 4.45315E-02 | None | None | None | None | N | None | 1.33739E-02 | 1.51404E-01 | 4.93421E-02 | 2.9683E-02 | 2.37177E-02 | None | 5.83852E-02 | 6.64557E-02 | 3.03503E-02 | 1.76483E-01 | 4.01914E-02 |
| R/H | rs4894028 |
-2.268 | 1.0 | D | 0.818 | 0.435 | None | gnomAD-4.0.0 | 4.52256E-02 | None | None | None | None | N | None | 1.2666E-02 | 1.80512E-01 | None | 2.93621E-02 | 1.49779E-02 | None | 5.87482E-02 | 4.85309E-02 | 3.1225E-02 | 1.72966E-01 | 4.76084E-02 |
| R/S | None | None | 1.0 | N | 0.75 | 0.485 | 0.5956732 | gnomAD-4.0.0 | 6.84244E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9952E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9895 | likely_pathogenic | 0.9827 | pathogenic | -1.94 | Destabilizing | 0.999 | D | 0.634 | neutral | None | None | None | None | N |
| R/C | 0.7855 | likely_pathogenic | 0.6937 | pathogenic | -1.893 | Destabilizing | 1.0 | D | 0.789 | deleterious | D | 0.5308667 | None | None | N |
| R/D | 0.9985 | likely_pathogenic | 0.9972 | pathogenic | -0.972 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| R/E | 0.982 | likely_pathogenic | 0.9691 | pathogenic | -0.767 | Destabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | N |
| R/F | 0.9968 | likely_pathogenic | 0.9929 | pathogenic | -1.271 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| R/G | 0.9842 | likely_pathogenic | 0.9737 | pathogenic | -2.274 | Highly Destabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.54871744 | None | None | N |
| R/H | 0.6702 | likely_pathogenic | 0.5676 | pathogenic | -2.157 | Highly Destabilizing | 1.0 | D | 0.818 | deleterious | D | 0.54897094 | None | None | N |
| R/I | 0.985 | likely_pathogenic | 0.9713 | pathogenic | -0.976 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| R/K | 0.6459 | likely_pathogenic | 0.605 | pathogenic | -1.341 | Destabilizing | 0.998 | D | 0.636 | neutral | None | None | None | None | N |
| R/L | 0.9694 | likely_pathogenic | 0.9521 | pathogenic | -0.976 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.5081541 | None | None | N |
| R/M | 0.9888 | likely_pathogenic | 0.9796 | pathogenic | -1.451 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| R/N | 0.9936 | likely_pathogenic | 0.9881 | pathogenic | -1.268 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| R/P | 0.9996 | likely_pathogenic | 0.9994 | pathogenic | -1.286 | Destabilizing | 1.0 | D | 0.791 | deleterious | D | 0.54922444 | None | None | N |
| R/Q | 0.602 | likely_pathogenic | 0.5224 | ambiguous | -1.169 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| R/S | 0.9914 | likely_pathogenic | 0.9845 | pathogenic | -2.162 | Highly Destabilizing | 1.0 | D | 0.75 | deleterious | N | 0.5111886 | None | None | N |
| R/T | 0.9894 | likely_pathogenic | 0.9806 | pathogenic | -1.748 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| R/V | 0.9861 | likely_pathogenic | 0.9745 | pathogenic | -1.286 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| R/W | 0.9497 | likely_pathogenic | 0.9068 | pathogenic | -0.818 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| R/Y | 0.9875 | likely_pathogenic | 0.9735 | pathogenic | -0.638 | Destabilizing | 1.0 | D | 0.82 | 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.