Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20806 | 62641;62642;62643 | chr2:178589309;178589308;178589307 | chr2:179454036;179454035;179454034 |
| N2AB | 19165 | 57718;57719;57720 | chr2:178589309;178589308;178589307 | chr2:179454036;179454035;179454034 |
| N2A | 18238 | 54937;54938;54939 | chr2:178589309;178589308;178589307 | chr2:179454036;179454035;179454034 |
| N2B | 11741 | 35446;35447;35448 | chr2:178589309;178589308;178589307 | chr2:179454036;179454035;179454034 |
| Novex-1 | 11866 | 35821;35822;35823 | chr2:178589309;178589308;178589307 | chr2:179454036;179454035;179454034 |
| Novex-2 | 11933 | 36022;36023;36024 | chr2:178589309;178589308;178589307 | chr2:179454036;179454035;179454034 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs1425140267  |
-0.77 | 0.928 | N | 0.647 | 0.551 | 0.390374949789 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.55E-05 | None | 0 | 0 | 0 |
| D/G | rs1425140267 |
-0.77 | 0.928 | N | 0.647 | 0.551 | 0.390374949789 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07039E-04 | 0 |
| D/G | rs1425140267 |
-0.77 | 0.928 | N | 0.647 | 0.551 | 0.390374949789 | gnomAD-4.0.0 | 3.84655E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.0222E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4929 | ambiguous | 0.56 | ambiguous | -0.385 | Destabilizing | 0.957 | D | 0.621 | neutral | N | 0.449886374 | None | None | N |
| D/C | 0.8835 | likely_pathogenic | 0.9173 | pathogenic | -0.111 | Destabilizing | 0.999 | D | 0.626 | neutral | None | None | None | None | N |
| D/E | 0.2722 | likely_benign | 0.3011 | benign | -0.447 | Destabilizing | 0.039 | N | 0.288 | neutral | N | 0.461930165 | None | None | N |
| D/F | 0.8628 | likely_pathogenic | 0.8805 | pathogenic | -0.23 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| D/G | 0.226 | likely_benign | 0.2484 | benign | -0.63 | Destabilizing | 0.928 | D | 0.647 | neutral | N | 0.460679371 | None | None | N |
| D/H | 0.7824 | likely_pathogenic | 0.8064 | pathogenic | -0.286 | Destabilizing | 0.997 | D | 0.609 | neutral | N | 0.4916744 | None | None | N |
| D/I | 0.849 | likely_pathogenic | 0.8827 | pathogenic | 0.226 | Stabilizing | 0.992 | D | 0.673 | neutral | None | None | None | None | N |
| D/K | 0.8546 | likely_pathogenic | 0.8658 | pathogenic | -0.035 | Destabilizing | 0.968 | D | 0.636 | neutral | None | None | None | None | N |
| D/L | 0.7316 | likely_pathogenic | 0.7724 | pathogenic | 0.226 | Stabilizing | 0.983 | D | 0.667 | neutral | None | None | None | None | N |
| D/M | 0.8919 | likely_pathogenic | 0.9145 | pathogenic | 0.414 | Stabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
| D/N | 0.2145 | likely_benign | 0.2178 | benign | -0.316 | Destabilizing | 0.978 | D | 0.599 | neutral | N | 0.444363124 | None | None | N |
| D/P | 0.9604 | likely_pathogenic | 0.9687 | pathogenic | 0.045 | Stabilizing | 0.992 | D | 0.647 | neutral | None | None | None | None | N |
| D/Q | 0.7252 | likely_pathogenic | 0.7594 | pathogenic | -0.257 | Destabilizing | 0.968 | D | 0.639 | neutral | None | None | None | None | N |
| D/R | 0.8549 | likely_pathogenic | 0.865 | pathogenic | 0.144 | Stabilizing | 0.983 | D | 0.641 | neutral | None | None | None | None | N |
| D/S | 0.3801 | ambiguous | 0.4284 | ambiguous | -0.46 | Destabilizing | 0.895 | D | 0.584 | neutral | None | None | None | None | N |
| D/T | 0.7016 | likely_pathogenic | 0.7386 | pathogenic | -0.273 | Destabilizing | 0.983 | D | 0.683 | prob.neutral | None | None | None | None | N |
| D/V | 0.6652 | likely_pathogenic | 0.7213 | pathogenic | 0.045 | Stabilizing | 0.978 | D | 0.675 | neutral | N | 0.521402543 | None | None | N |
| D/W | 0.963 | likely_pathogenic | 0.9696 | pathogenic | -0.088 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| D/Y | 0.5578 | ambiguous | 0.5876 | pathogenic | -0.007 | Destabilizing | 0.999 | D | 0.635 | neutral | N | 0.495713324 | 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.