Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28307 | 85144;85145;85146 | chr2:178561213;178561212;178561211 | chr2:179425940;179425939;179425938 |
| N2AB | 26666 | 80221;80222;80223 | chr2:178561213;178561212;178561211 | chr2:179425940;179425939;179425938 |
| N2A | 25739 | 77440;77441;77442 | chr2:178561213;178561212;178561211 | chr2:179425940;179425939;179425938 |
| N2B | 19242 | 57949;57950;57951 | chr2:178561213;178561212;178561211 | chr2:179425940;179425939;179425938 |
| Novex-1 | 19367 | 58324;58325;58326 | chr2:178561213;178561212;178561211 | chr2:179425940;179425939;179425938 |
| Novex-2 | 19434 | 58525;58526;58527 | chr2:178561213;178561212;178561211 | chr2:179425940;179425939;179425938 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1224788527  |
None | 0.029 | N | 0.417 | 0.223 | 0.560453403006 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1224788527 |
None | 0.029 | N | 0.417 | 0.223 | 0.560453403006 | gnomAD-4.0.0 | 3.71872E-06 | None | None | None | None | N | None | 2.66994E-05 | 0 | None | 0 | 0 | None | 1.56681E-05 | 0 | 2.54277E-06 | 0 | 0 |
| I/V | None | None | None | N | 0.169 | 0.077 | 0.141422826196 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8299 | likely_pathogenic | 0.7946 | pathogenic | -2.158 | Highly Destabilizing | 0.016 | N | 0.369 | neutral | None | None | None | None | N |
| I/C | 0.8235 | likely_pathogenic | 0.8069 | pathogenic | -1.467 | Destabilizing | 0.356 | N | 0.51 | neutral | None | None | None | None | N |
| I/D | 0.9791 | likely_pathogenic | 0.9732 | pathogenic | -1.967 | Destabilizing | 0.356 | N | 0.529 | neutral | None | None | None | None | N |
| I/E | 0.9508 | likely_pathogenic | 0.9378 | pathogenic | -1.772 | Destabilizing | 0.356 | N | 0.546 | neutral | None | None | None | None | N |
| I/F | 0.6558 | likely_pathogenic | 0.6149 | pathogenic | -1.248 | Destabilizing | 0.072 | N | 0.499 | neutral | None | None | None | None | N |
| I/G | 0.9602 | likely_pathogenic | 0.9485 | pathogenic | -2.683 | Highly Destabilizing | 0.136 | N | 0.515 | neutral | None | None | None | None | N |
| I/H | 0.9195 | likely_pathogenic | 0.9013 | pathogenic | -2.104 | Highly Destabilizing | 0.864 | D | 0.53 | neutral | None | None | None | None | N |
| I/K | 0.8865 | likely_pathogenic | 0.8696 | pathogenic | -1.412 | Destabilizing | 0.106 | N | 0.535 | neutral | N | 0.477076323 | None | None | N |
| I/L | 0.1936 | likely_benign | 0.194 | benign | -0.674 | Destabilizing | None | N | 0.161 | neutral | N | 0.454968828 | None | None | N |
| I/M | 0.2872 | likely_benign | 0.2683 | benign | -0.685 | Destabilizing | 0.171 | N | 0.548 | neutral | N | 0.48986466 | None | None | N |
| I/N | 0.7691 | likely_pathogenic | 0.7158 | pathogenic | -1.61 | Destabilizing | 0.628 | D | 0.539 | neutral | None | None | None | None | N |
| I/P | 0.9596 | likely_pathogenic | 0.9545 | pathogenic | -1.146 | Destabilizing | 0.356 | N | 0.529 | neutral | None | None | None | None | N |
| I/Q | 0.9021 | likely_pathogenic | 0.877 | pathogenic | -1.511 | Destabilizing | 0.628 | D | 0.541 | neutral | None | None | None | None | N |
| I/R | 0.8523 | likely_pathogenic | 0.8308 | pathogenic | -1.186 | Destabilizing | 0.295 | N | 0.541 | neutral | N | 0.467859611 | None | None | N |
| I/S | 0.7931 | likely_pathogenic | 0.742 | pathogenic | -2.373 | Highly Destabilizing | 0.072 | N | 0.494 | neutral | None | None | None | None | N |
| I/T | 0.6695 | likely_pathogenic | 0.619 | pathogenic | -2.028 | Highly Destabilizing | 0.029 | N | 0.417 | neutral | N | 0.50162105 | None | None | N |
| I/V | 0.0849 | likely_benign | 0.0827 | benign | -1.146 | Destabilizing | None | N | 0.169 | neutral | N | 0.394765731 | None | None | N |
| I/W | 0.9824 | likely_pathogenic | 0.9794 | pathogenic | -1.557 | Destabilizing | 0.864 | D | 0.557 | neutral | None | None | None | None | N |
| I/Y | 0.9106 | likely_pathogenic | 0.8902 | pathogenic | -1.242 | Destabilizing | 0.356 | N | 0.536 | 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.