Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23461 | 70606;70607;70608 | chr2:178575751;178575750;178575749 | chr2:179440478;179440477;179440476 |
| N2AB | 21820 | 65683;65684;65685 | chr2:178575751;178575750;178575749 | chr2:179440478;179440477;179440476 |
| N2A | 20893 | 62902;62903;62904 | chr2:178575751;178575750;178575749 | chr2:179440478;179440477;179440476 |
| N2B | 14396 | 43411;43412;43413 | chr2:178575751;178575750;178575749 | chr2:179440478;179440477;179440476 |
| Novex-1 | 14521 | 43786;43787;43788 | chr2:178575751;178575750;178575749 | chr2:179440478;179440477;179440476 |
| Novex-2 | 14588 | 43987;43988;43989 | chr2:178575751;178575750;178575749 | chr2:179440478;179440477;179440476 |
| 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/M | None | None | 0.484 | N | 0.348 | 0.111 | 0.3571064206 | gnomAD-4.0.0 | 1.59186E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8595E-06 | 0 | 0 |
| I/R | rs775762472  |
0.241 | 0.484 | N | 0.453 | 0.326 | 0.53787198782 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65673E-04 |
| I/R | rs775762472 |
0.241 | 0.484 | N | 0.453 | 0.326 | 0.53787198782 | gnomAD-4.0.0 | 1.59189E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43303E-05 | 0 |
| I/V | rs1170300318 |
-0.205 | None | N | 0.107 | 0.037 | 0.257292322809 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs1170300318 |
-0.205 | None | N | 0.107 | 0.037 | 0.257292322809 | gnomAD-4.0.0 | 3.18369E-06 | None | None | None | None | I | None | 0 | 4.57352E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3753 | ambiguous | 0.382 | ambiguous | -0.625 | Destabilizing | 0.081 | N | 0.387 | neutral | None | None | None | None | I |
| I/C | 0.7538 | likely_pathogenic | 0.7799 | pathogenic | -0.684 | Destabilizing | 0.935 | D | 0.393 | neutral | None | None | None | None | I |
| I/D | 0.7728 | likely_pathogenic | 0.7449 | pathogenic | -0.073 | Destabilizing | 0.001 | N | 0.368 | neutral | None | None | None | None | I |
| I/E | 0.7117 | likely_pathogenic | 0.6893 | pathogenic | -0.157 | Destabilizing | 0.081 | N | 0.453 | neutral | None | None | None | None | I |
| I/F | 0.2196 | likely_benign | 0.2972 | benign | -0.599 | Destabilizing | 0.001 | N | 0.225 | neutral | None | None | None | None | I |
| I/G | 0.7768 | likely_pathogenic | 0.7699 | pathogenic | -0.794 | Destabilizing | 0.38 | N | 0.441 | neutral | None | None | None | None | I |
| I/H | 0.5819 | likely_pathogenic | 0.6193 | pathogenic | -0.114 | Destabilizing | 0.935 | D | 0.433 | neutral | None | None | None | None | I |
| I/K | 0.6291 | likely_pathogenic | 0.6535 | pathogenic | -0.358 | Destabilizing | 0.317 | N | 0.461 | neutral | N | 0.507528302 | None | None | I |
| I/L | 0.0874 | likely_benign | 0.0972 | benign | -0.301 | Destabilizing | 0.027 | N | 0.332 | neutral | N | 0.448461356 | None | None | I |
| I/M | 0.106 | likely_benign | 0.1275 | benign | -0.415 | Destabilizing | 0.484 | N | 0.348 | neutral | N | 0.466223315 | None | None | I |
| I/N | 0.2675 | likely_benign | 0.2553 | benign | -0.176 | Destabilizing | 0.235 | N | 0.468 | neutral | None | None | None | None | I |
| I/P | 0.9159 | likely_pathogenic | 0.9265 | pathogenic | -0.375 | Destabilizing | 0.555 | D | 0.463 | neutral | None | None | None | None | I |
| I/Q | 0.5545 | ambiguous | 0.5477 | ambiguous | -0.372 | Destabilizing | 0.555 | D | 0.455 | neutral | None | None | None | None | I |
| I/R | 0.4974 | ambiguous | 0.5352 | ambiguous | 0.152 | Stabilizing | 0.484 | N | 0.453 | neutral | N | 0.479149623 | None | None | I |
| I/S | 0.3225 | likely_benign | 0.3225 | benign | -0.645 | Destabilizing | 0.149 | N | 0.432 | neutral | None | None | None | None | I |
| I/T | 0.1698 | likely_benign | 0.1751 | benign | -0.616 | Destabilizing | 0.117 | N | 0.412 | neutral | N | 0.458235633 | None | None | I |
| I/V | 0.0986 | likely_benign | 0.0903 | benign | -0.375 | Destabilizing | None | N | 0.107 | neutral | N | 0.461102579 | None | None | I |
| I/W | 0.7849 | likely_pathogenic | 0.8494 | pathogenic | -0.619 | Destabilizing | 0.824 | D | 0.502 | neutral | None | None | None | None | I |
| I/Y | 0.5702 | likely_pathogenic | 0.6331 | pathogenic | -0.371 | Destabilizing | 0.235 | N | 0.381 | neutral | None | None | None | None | I |
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.