Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27443 | 82552;82553;82554 | chr2:178563805;178563804;178563803 | chr2:179428532;179428531;179428530 |
| N2AB | 25802 | 77629;77630;77631 | chr2:178563805;178563804;178563803 | chr2:179428532;179428531;179428530 |
| N2A | 24875 | 74848;74849;74850 | chr2:178563805;178563804;178563803 | chr2:179428532;179428531;179428530 |
| N2B | 18378 | 55357;55358;55359 | chr2:178563805;178563804;178563803 | chr2:179428532;179428531;179428530 |
| Novex-1 | 18503 | 55732;55733;55734 | chr2:178563805;178563804;178563803 | chr2:179428532;179428531;179428530 |
| Novex-2 | 18570 | 55933;55934;55935 | chr2:178563805;178563804;178563803 | chr2:179428532;179428531;179428530 |
| 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 | rs755125180  |
-1.497 | 1.0 | D | 0.737 | 0.471 | 0.754919144752 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| R/C | rs755125180 |
-1.497 | 1.0 | D | 0.737 | 0.471 | 0.754919144752 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs755125180 |
-1.497 | 1.0 | D | 0.737 | 0.471 | 0.754919144752 | gnomAD-4.0.0 | 6.81732E-06 | None | None | None | None | N | None | 0 | 3.33556E-05 | None | 0 | 2.23095E-05 | None | 0 | 0 | 5.08586E-06 | 1.09789E-05 | 1.60108E-05 |
| R/H | rs551496477 |
-1.962 | 0.999 | D | 0.589 | 0.601 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| R/H | rs551496477 |
-1.962 | 0.999 | D | 0.589 | 0.601 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs551496477 |
-1.962 | 0.999 | D | 0.589 | 0.601 | None | gnomAD-4.0.0 | 1.92125E-05 | None | None | None | None | N | None | 1.33558E-05 | 0 | None | 0 | 2.23045E-05 | None | 0 | 0 | 2.3734E-05 | 0 | 1.60113E-05 |
| R/L | rs551496477 |
-0.551 | 0.954 | N | 0.6 | 0.551 | 0.638463085031 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11582E-04 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/L | rs551496477 |
-0.551 | 0.954 | N | 0.6 | 0.551 | 0.638463085031 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93349E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/L | rs551496477 |
-0.551 | 0.954 | N | 0.6 | 0.551 | 0.638463085031 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/L | rs551496477 |
-0.551 | 0.954 | N | 0.6 | 0.551 | 0.638463085031 | gnomAD-4.0.0 | 4.9577E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.46209E-05 | None | 0 | 0 | 5.0859E-06 | 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 | 0.9844 | likely_pathogenic | 0.9818 | pathogenic | -1.676 | Destabilizing | 0.845 | D | 0.591 | neutral | None | None | None | None | N |
| R/C | 0.6704 | likely_pathogenic | 0.6079 | pathogenic | -1.634 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | D | 0.534981302 | None | None | N |
| R/D | 0.9977 | likely_pathogenic | 0.9969 | pathogenic | -1.067 | Destabilizing | 0.987 | D | 0.607 | neutral | None | None | None | None | N |
| R/E | 0.9673 | likely_pathogenic | 0.9612 | pathogenic | -0.857 | Destabilizing | 0.916 | D | 0.574 | neutral | None | None | None | None | N |
| R/F | 0.9945 | likely_pathogenic | 0.9926 | pathogenic | -0.696 | Destabilizing | 0.999 | D | 0.744 | deleterious | None | None | None | None | N |
| R/G | 0.9729 | likely_pathogenic | 0.9653 | pathogenic | -1.997 | Destabilizing | 0.954 | D | 0.593 | neutral | D | 0.557605008 | None | None | N |
| R/H | 0.5529 | ambiguous | 0.455 | ambiguous | -1.871 | Destabilizing | 0.999 | D | 0.589 | neutral | D | 0.557858497 | None | None | N |
| R/I | 0.9785 | likely_pathogenic | 0.9725 | pathogenic | -0.742 | Destabilizing | 0.987 | D | 0.73 | prob.delet. | None | None | None | None | N |
| R/K | 0.5878 | likely_pathogenic | 0.5856 | pathogenic | -1.213 | Destabilizing | 0.818 | D | 0.649 | neutral | None | None | None | None | N |
| R/L | 0.9482 | likely_pathogenic | 0.9383 | pathogenic | -0.742 | Destabilizing | 0.954 | D | 0.6 | neutral | N | 0.515560374 | None | None | N |
| R/M | 0.977 | likely_pathogenic | 0.9708 | pathogenic | -1.29 | Destabilizing | 0.999 | D | 0.624 | neutral | None | None | None | None | N |
| R/N | 0.9919 | likely_pathogenic | 0.9885 | pathogenic | -1.356 | Destabilizing | 0.987 | D | 0.529 | neutral | None | None | None | None | N |
| R/P | 0.9993 | likely_pathogenic | 0.999 | pathogenic | -1.043 | Destabilizing | 0.062 | N | 0.589 | neutral | D | 0.558111987 | None | None | N |
| R/Q | 0.5408 | ambiguous | 0.4903 | ambiguous | -1.055 | Destabilizing | 0.987 | D | 0.538 | neutral | None | None | None | None | N |
| R/S | 0.9839 | likely_pathogenic | 0.9796 | pathogenic | -2.021 | Highly Destabilizing | 0.954 | D | 0.554 | neutral | N | 0.507732333 | None | None | N |
| R/T | 0.9809 | likely_pathogenic | 0.9721 | pathogenic | -1.622 | Destabilizing | 0.916 | D | 0.556 | neutral | None | None | None | None | N |
| R/V | 0.9804 | likely_pathogenic | 0.9752 | pathogenic | -1.043 | Destabilizing | 0.987 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/W | 0.8712 | likely_pathogenic | 0.8312 | pathogenic | -0.409 | Destabilizing | 0.999 | D | 0.67 | neutral | None | None | None | None | N |
| R/Y | 0.9763 | likely_pathogenic | 0.9691 | pathogenic | -0.274 | Destabilizing | 0.996 | D | 0.706 | 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.