Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28129 | 84610;84611;84612 | chr2:178561747;178561746;178561745 | chr2:179426474;179426473;179426472 |
| N2AB | 26488 | 79687;79688;79689 | chr2:178561747;178561746;178561745 | chr2:179426474;179426473;179426472 |
| N2A | 25561 | 76906;76907;76908 | chr2:178561747;178561746;178561745 | chr2:179426474;179426473;179426472 |
| N2B | 19064 | 57415;57416;57417 | chr2:178561747;178561746;178561745 | chr2:179426474;179426473;179426472 |
| Novex-1 | 19189 | 57790;57791;57792 | chr2:178561747;178561746;178561745 | chr2:179426474;179426473;179426472 |
| Novex-2 | 19256 | 57991;57992;57993 | chr2:178561747;178561746;178561745 | chr2:179426474;179426473;179426472 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/D | None | None | 0.995 | D | 0.883 | 0.785 | 0.925069995079 | gnomAD-4.0.0 | 1.59238E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4332E-05 | 0 |
| V/F | rs752974639  |
-1.667 | 0.968 | D | 0.699 | 0.546 | 0.850827110383 | gnomAD-2.1.1 | 4.3E-05 | None | None | None | None | N | None | 4.14E-05 | 8.5E-05 | None | 0 | 0 | None | 0 | None | 0 | 6.27E-05 | 0 |
| V/F | rs752974639 |
-1.667 | 0.968 | D | 0.699 | 0.546 | 0.850827110383 | gnomAD-3.1.2 | 3.28E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 4.77555E-04 |
| V/F | rs752974639 |
-1.667 | 0.968 | D | 0.699 | 0.546 | 0.850827110383 | gnomAD-4.0.0 | 7.06613E-05 | None | None | None | None | N | None | 2.67058E-05 | 1.50105E-04 | None | 0 | 0 | None | 0 | 0 | 7.79906E-05 | 0 | 1.76152E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7482 | likely_pathogenic | 0.7596 | pathogenic | -2.512 | Highly Destabilizing | 0.78 | D | 0.531 | neutral | D | 0.538160621 | None | None | N |
| V/C | 0.942 | likely_pathogenic | 0.9378 | pathogenic | -1.712 | Destabilizing | 0.999 | D | 0.738 | prob.delet. | None | None | None | None | N |
| V/D | 0.9967 | likely_pathogenic | 0.9962 | pathogenic | -3.252 | Highly Destabilizing | 0.995 | D | 0.883 | deleterious | D | 0.645503027 | None | None | N |
| V/E | 0.9909 | likely_pathogenic | 0.9898 | pathogenic | -2.946 | Highly Destabilizing | 0.996 | D | 0.831 | deleterious | None | None | None | None | N |
| V/F | 0.8359 | likely_pathogenic | 0.7927 | pathogenic | -1.371 | Destabilizing | 0.968 | D | 0.699 | prob.neutral | D | 0.578977487 | None | None | N |
| V/G | 0.8776 | likely_pathogenic | 0.8731 | pathogenic | -3.063 | Highly Destabilizing | 0.995 | D | 0.861 | deleterious | D | 0.645503027 | None | None | N |
| V/H | 0.9967 | likely_pathogenic | 0.996 | pathogenic | -2.867 | Highly Destabilizing | 0.999 | D | 0.887 | deleterious | None | None | None | None | N |
| V/I | 0.1035 | likely_benign | 0.0959 | benign | -0.882 | Destabilizing | 0.011 | N | 0.171 | neutral | N | 0.485983247 | None | None | N |
| V/K | 0.9938 | likely_pathogenic | 0.9918 | pathogenic | -1.897 | Destabilizing | 0.988 | D | 0.832 | deleterious | None | None | None | None | N |
| V/L | 0.6437 | likely_pathogenic | 0.5791 | pathogenic | -0.882 | Destabilizing | 0.437 | N | 0.257 | neutral | N | 0.521925563 | None | None | N |
| V/M | 0.7478 | likely_pathogenic | 0.6916 | pathogenic | -1.185 | Destabilizing | 0.976 | D | 0.609 | neutral | None | None | None | None | N |
| V/N | 0.9889 | likely_pathogenic | 0.9869 | pathogenic | -2.567 | Highly Destabilizing | 0.996 | D | 0.898 | deleterious | None | None | None | None | N |
| V/P | 0.9938 | likely_pathogenic | 0.9904 | pathogenic | -1.413 | Destabilizing | 0.996 | D | 0.846 | deleterious | None | None | None | None | N |
| V/Q | 0.9889 | likely_pathogenic | 0.9873 | pathogenic | -2.207 | Highly Destabilizing | 0.996 | D | 0.877 | deleterious | None | None | None | None | N |
| V/R | 0.9849 | likely_pathogenic | 0.9822 | pathogenic | -2.013 | Highly Destabilizing | 0.996 | D | 0.895 | deleterious | None | None | None | None | N |
| V/S | 0.9378 | likely_pathogenic | 0.9383 | pathogenic | -2.988 | Highly Destabilizing | 0.988 | D | 0.791 | deleterious | None | None | None | None | N |
| V/T | 0.8834 | likely_pathogenic | 0.8839 | pathogenic | -2.542 | Highly Destabilizing | 0.919 | D | 0.572 | neutral | None | None | None | None | N |
| V/W | 0.997 | likely_pathogenic | 0.9958 | pathogenic | -1.833 | Destabilizing | 0.999 | D | 0.864 | deleterious | None | None | None | None | N |
| V/Y | 0.9822 | likely_pathogenic | 0.9768 | pathogenic | -1.646 | Destabilizing | 0.996 | D | 0.708 | prob.delet. | 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.