Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33777 | 101554;101555;101556 | chr2:178535286;178535285;178535284 | chr2:179400013;179400012;179400011 |
| N2AB | 32136 | 96631;96632;96633 | chr2:178535286;178535285;178535284 | chr2:179400013;179400012;179400011 |
| N2A | 31209 | 93850;93851;93852 | chr2:178535286;178535285;178535284 | chr2:179400013;179400012;179400011 |
| N2B | 24712 | 74359;74360;74361 | chr2:178535286;178535285;178535284 | chr2:179400013;179400012;179400011 |
| Novex-1 | 24837 | 74734;74735;74736 | chr2:178535286;178535285;178535284 | chr2:179400013;179400012;179400011 |
| Novex-2 | 24904 | 74935;74936;74937 | chr2:178535286;178535285;178535284 | chr2:179400013;179400012;179400011 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs983842520  |
None | 0.948 | N | 0.678 | 0.378 | 0.596065454935 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.77555E-04 |
| S/L | rs983842520 |
None | 0.948 | N | 0.678 | 0.378 | 0.596065454935 | gnomAD-4.0.0 | 4.05978E-06 | None | None | None | None | N | None | 0 | 6.15536E-05 | None | 0 | 0 | None | 0 | 0 | 2.40981E-06 | 0 | 3.40229E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2393 | likely_benign | 0.2266 | benign | -0.722 | Destabilizing | 0.034 | N | 0.434 | neutral | N | 0.489542854 | None | None | N |
| S/C | 0.3032 | likely_benign | 0.2827 | benign | -0.453 | Destabilizing | 0.997 | D | 0.615 | neutral | None | None | None | None | N |
| S/D | 0.9535 | likely_pathogenic | 0.9679 | pathogenic | -0.336 | Destabilizing | 0.541 | D | 0.622 | neutral | None | None | None | None | N |
| S/E | 0.9809 | likely_pathogenic | 0.9855 | pathogenic | -0.264 | Destabilizing | 0.623 | D | 0.616 | neutral | None | None | None | None | N |
| S/F | 0.9373 | likely_pathogenic | 0.9437 | pathogenic | -0.625 | Destabilizing | 0.997 | D | 0.692 | prob.delet. | None | None | None | None | N |
| S/G | 0.3243 | likely_benign | 0.3415 | ambiguous | -1.043 | Destabilizing | 0.686 | D | 0.59 | neutral | None | None | None | None | N |
| S/H | 0.9629 | likely_pathogenic | 0.9721 | pathogenic | -1.434 | Destabilizing | 0.999 | D | 0.611 | neutral | None | None | None | None | N |
| S/I | 0.7752 | likely_pathogenic | 0.7951 | pathogenic | 0.05 | Stabilizing | 0.988 | D | 0.637 | neutral | None | None | None | None | N |
| S/K | 0.9953 | likely_pathogenic | 0.9973 | pathogenic | -0.521 | Destabilizing | 0.993 | D | 0.621 | neutral | None | None | None | None | N |
| S/L | 0.5114 | ambiguous | 0.5459 | ambiguous | 0.05 | Stabilizing | 0.948 | D | 0.678 | prob.neutral | N | 0.495681692 | None | None | N |
| S/M | 0.6778 | likely_pathogenic | 0.6963 | pathogenic | 0.092 | Stabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | N |
| S/N | 0.7726 | likely_pathogenic | 0.8335 | pathogenic | -0.66 | Destabilizing | 0.121 | N | 0.653 | prob.neutral | None | None | None | None | N |
| S/P | 0.9724 | likely_pathogenic | 0.9755 | pathogenic | -0.172 | Destabilizing | 0.864 | D | 0.646 | neutral | N | 0.504319427 | None | None | N |
| S/Q | 0.9749 | likely_pathogenic | 0.9804 | pathogenic | -0.653 | Destabilizing | 0.969 | D | 0.602 | neutral | None | None | None | None | N |
| S/R | 0.9918 | likely_pathogenic | 0.9946 | pathogenic | -0.621 | Destabilizing | 0.998 | D | 0.623 | neutral | None | None | None | None | N |
| S/T | 0.0818 | likely_benign | 0.1072 | benign | -0.587 | Destabilizing | None | N | 0.237 | neutral | N | 0.491356489 | None | None | N |
| S/V | 0.6359 | likely_pathogenic | 0.6511 | pathogenic | -0.172 | Destabilizing | 0.9 | D | 0.681 | prob.neutral | None | None | None | None | N |
| S/W | 0.9636 | likely_pathogenic | 0.9706 | pathogenic | -0.68 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| S/Y | 0.9393 | likely_pathogenic | 0.9512 | pathogenic | -0.361 | Destabilizing | 0.988 | D | 0.675 | prob.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.