Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14464 | 43615;43616;43617 | chr2:178632616;178632615;178632614 | chr2:179497343;179497342;179497341 |
| N2AB | 12823 | 38692;38693;38694 | chr2:178632616;178632615;178632614 | chr2:179497343;179497342;179497341 |
| N2A | 11896 | 35911;35912;35913 | chr2:178632616;178632615;178632614 | chr2:179497343;179497342;179497341 |
| N2B | 5399 | 16420;16421;16422 | chr2:178632616;178632615;178632614 | chr2:179497343;179497342;179497341 |
| Novex-1 | 5524 | 16795;16796;16797 | chr2:178632616;178632615;178632614 | chr2:179497343;179497342;179497341 |
| Novex-2 | 5591 | 16996;16997;16998 | chr2:178632616;178632615;178632614 | chr2:179497343;179497342;179497341 |
| 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 | rs370601384  |
1.039 | 0.002 | N | 0.441 | 0.32 | 0.529161192476 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 6.46E-05 | 1.44919E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| M/I | rs370601384 |
1.039 | 0.002 | N | 0.441 | 0.32 | 0.529161192476 | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 4.82E-05 | 3.93649E-04 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| M/I | rs370601384 |
1.039 | 0.002 | N | 0.441 | 0.32 | 0.529161192476 | gnomAD-4.0.0 | 2.47932E-05 | None | None | None | None | N | None | 2.67023E-05 | 1.83468E-04 | None | 0 | 0 | None | 0 | 0 | 2.03462E-05 | 0 | 4.80507E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.6696 | likely_pathogenic | 0.6927 | pathogenic | -0.522 | Destabilizing | 0.014 | N | 0.633 | neutral | None | None | None | None | N |
| M/C | 0.8581 | likely_pathogenic | 0.8557 | pathogenic | -1.932 | Destabilizing | 0.628 | D | 0.79 | deleterious | None | None | None | None | N |
| M/D | 0.9957 | likely_pathogenic | 0.9963 | pathogenic | -1.431 | Destabilizing | 0.325 | N | 0.842 | deleterious | None | None | None | None | N |
| M/E | 0.9684 | likely_pathogenic | 0.9706 | pathogenic | -1.204 | Destabilizing | 0.136 | N | 0.804 | deleterious | None | None | None | None | N |
| M/F | 0.4619 | ambiguous | 0.5103 | ambiguous | 0.417 | Stabilizing | 0.016 | N | 0.58 | neutral | None | None | None | None | N |
| M/G | 0.9326 | likely_pathogenic | 0.9395 | pathogenic | -0.922 | Destabilizing | 0.136 | N | 0.803 | deleterious | None | None | None | None | N |
| M/H | 0.9614 | likely_pathogenic | 0.9637 | pathogenic | -1.142 | Destabilizing | 0.628 | D | 0.859 | deleterious | None | None | None | None | N |
| M/I | 0.3116 | likely_benign | 0.3008 | benign | 0.633 | Stabilizing | 0.002 | N | 0.441 | neutral | N | 0.466756283 | None | None | N |
| M/K | 0.8733 | likely_pathogenic | 0.8702 | pathogenic | -0.398 | Destabilizing | 0.047 | N | 0.691 | prob.neutral | D | 0.522174224 | None | None | N |
| M/L | 0.074 | likely_benign | 0.0831 | benign | 0.633 | Stabilizing | None | N | 0.247 | neutral | N | 0.23788887 | None | None | N |
| M/N | 0.9738 | likely_pathogenic | 0.9769 | pathogenic | -1.034 | Destabilizing | 0.325 | N | 0.832 | deleterious | None | None | None | None | N |
| M/P | 0.9884 | likely_pathogenic | 0.9912 | pathogenic | 0.261 | Stabilizing | 0.325 | N | 0.821 | deleterious | None | None | None | None | N |
| M/Q | 0.882 | likely_pathogenic | 0.8858 | pathogenic | -0.584 | Destabilizing | 0.325 | N | 0.649 | neutral | None | None | None | None | N |
| M/R | 0.8563 | likely_pathogenic | 0.8589 | pathogenic | -1.05 | Destabilizing | 0.106 | N | 0.731 | prob.delet. | D | 0.522174224 | None | None | N |
| M/S | 0.9194 | likely_pathogenic | 0.9317 | pathogenic | -1.167 | Destabilizing | 0.061 | N | 0.697 | prob.neutral | None | None | None | None | N |
| M/T | 0.6837 | likely_pathogenic | 0.6992 | pathogenic | -0.819 | Destabilizing | 0.024 | N | 0.678 | prob.neutral | D | 0.522074413 | None | None | N |
| M/V | 0.1062 | likely_benign | 0.1043 | benign | 0.261 | Stabilizing | 0.002 | N | 0.431 | neutral | N | 0.466946388 | None | None | N |
| M/W | 0.9035 | likely_pathogenic | 0.9025 | pathogenic | 0.026 | Stabilizing | 0.864 | D | 0.793 | deleterious | None | None | None | None | N |
| M/Y | 0.9014 | likely_pathogenic | 0.9065 | pathogenic | 0.176 | Stabilizing | 0.136 | N | 0.753 | deleterious | 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.