Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28774 | 86545;86546;86547 | chr2:178559812;178559811;178559810 | chr2:179424539;179424538;179424537 |
| N2AB | 27133 | 81622;81623;81624 | chr2:178559812;178559811;178559810 | chr2:179424539;179424538;179424537 |
| N2A | 26206 | 78841;78842;78843 | chr2:178559812;178559811;178559810 | chr2:179424539;179424538;179424537 |
| N2B | 19709 | 59350;59351;59352 | chr2:178559812;178559811;178559810 | chr2:179424539;179424538;179424537 |
| Novex-1 | 19834 | 59725;59726;59727 | chr2:178559812;178559811;178559810 | chr2:179424539;179424538;179424537 |
| Novex-2 | 19901 | 59926;59927;59928 | chr2:178559812;178559811;178559810 | chr2:179424539;179424538;179424537 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | 0.002 | N | 0.332 | 0.136 | 0.326616659874 | gnomAD-4.0.0 | 1.37197E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99944E-07 | 1.16355E-05 | 0 |
| M/T | rs766812574  |
-1.359 | 0.213 | N | 0.6 | 0.421 | None | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| M/T | rs766812574 |
-1.359 | 0.213 | N | 0.6 | 0.421 | None | gnomAD-4.0.0 | 4.80091E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.58615E-06 | 0 | 0 |
| M/V | None | None | 0.017 | N | 0.415 | 0.125 | 0.377799810692 | gnomAD-4.0.0 | 1.37168E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99826E-07 | 1.16244E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8115 | likely_pathogenic | 0.8006 | pathogenic | -1.45 | Destabilizing | 0.129 | N | 0.572 | neutral | None | None | None | None | N |
| M/C | 0.8888 | likely_pathogenic | 0.887 | pathogenic | -1.324 | Destabilizing | 0.94 | D | 0.717 | prob.delet. | None | None | None | None | N |
| M/D | 0.999 | likely_pathogenic | 0.9989 | pathogenic | -0.905 | Destabilizing | 0.716 | D | 0.765 | deleterious | None | None | None | None | N |
| M/E | 0.9907 | likely_pathogenic | 0.99 | pathogenic | -0.675 | Destabilizing | 0.418 | N | 0.693 | prob.neutral | None | None | None | None | N |
| M/F | 0.5972 | likely_pathogenic | 0.5803 | pathogenic | -0.52 | Destabilizing | 0.418 | N | 0.607 | neutral | None | None | None | None | N |
| M/G | 0.9751 | likely_pathogenic | 0.9729 | pathogenic | -1.891 | Destabilizing | 0.264 | N | 0.709 | prob.delet. | None | None | None | None | N |
| M/H | 0.9856 | likely_pathogenic | 0.9833 | pathogenic | -1.662 | Destabilizing | 0.983 | D | 0.784 | deleterious | None | None | None | None | N |
| M/I | 0.4412 | ambiguous | 0.4466 | ambiguous | -0.185 | Destabilizing | 0.002 | N | 0.332 | neutral | N | 0.386429541 | None | None | N |
| M/K | 0.9512 | likely_pathogenic | 0.9466 | pathogenic | -0.449 | Destabilizing | 0.351 | N | 0.589 | neutral | N | 0.485732463 | None | None | N |
| M/L | 0.1156 | likely_benign | 0.1239 | benign | -0.185 | Destabilizing | None | N | 0.239 | neutral | N | 0.356018129 | None | None | N |
| M/N | 0.9907 | likely_pathogenic | 0.9901 | pathogenic | -0.875 | Destabilizing | 0.716 | D | 0.751 | deleterious | None | None | None | None | N |
| M/P | 0.997 | likely_pathogenic | 0.9969 | pathogenic | -0.59 | Destabilizing | 0.836 | D | 0.749 | deleterious | None | None | None | None | N |
| M/Q | 0.9489 | likely_pathogenic | 0.9415 | pathogenic | -0.477 | Destabilizing | 0.716 | D | 0.649 | neutral | None | None | None | None | N |
| M/R | 0.9537 | likely_pathogenic | 0.9486 | pathogenic | -0.89 | Destabilizing | 0.655 | D | 0.693 | prob.neutral | N | 0.485732463 | None | None | N |
| M/S | 0.9648 | likely_pathogenic | 0.9608 | pathogenic | -1.39 | Destabilizing | 0.01 | N | 0.49 | neutral | None | None | None | None | N |
| M/T | 0.8806 | likely_pathogenic | 0.8653 | pathogenic | -1.011 | Destabilizing | 0.213 | N | 0.6 | neutral | N | 0.485478974 | None | None | N |
| M/V | 0.1192 | likely_benign | 0.1177 | benign | -0.59 | Destabilizing | 0.017 | N | 0.415 | neutral | N | 0.456617558 | None | None | N |
| M/W | 0.9678 | likely_pathogenic | 0.9637 | pathogenic | -0.718 | Destabilizing | 0.983 | D | 0.71 | prob.delet. | None | None | None | None | N |
| M/Y | 0.944 | likely_pathogenic | 0.9401 | pathogenic | -0.619 | Destabilizing | 0.836 | D | 0.704 | 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.