Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33053 | 99382;99383;99384 | chr2:178538672;178538671;178538670 | chr2:179403399;179403398;179403397 |
| N2AB | 31412 | 94459;94460;94461 | chr2:178538672;178538671;178538670 | chr2:179403399;179403398;179403397 |
| N2A | 30485 | 91678;91679;91680 | chr2:178538672;178538671;178538670 | chr2:179403399;179403398;179403397 |
| N2B | 23988 | 72187;72188;72189 | chr2:178538672;178538671;178538670 | chr2:179403399;179403398;179403397 |
| Novex-1 | 24113 | 72562;72563;72564 | chr2:178538672;178538671;178538670 | chr2:179403399;179403398;179403397 |
| Novex-2 | 24180 | 72763;72764;72765 | chr2:178538672;178538671;178538670 | chr2:179403399;179403398;179403397 |
| 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/N | None | None | None | N | 0.444 | 0.122 | 0.43742076 | gnomAD-4.0.0 | 6.84222E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99499E-07 | 0 | 0 |
| I/T | rs1692880660  |
None | None | N | 0.219 | 0.076 | 0.35731348 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1692880660 |
None | None | N | 0.219 | 0.076 | 0.35731348 | gnomAD-4.0.0 | 1.23948E-06 | None | None | None | None | N | None | 1.33558E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60133E-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 | 0.5407 | ambiguous | 0.6134 | pathogenic | -2.14 | Highly Destabilizing | 0.007 | N | 0.317 | neutral | None | None | None | None | N |
| I/C | 0.6143 | likely_pathogenic | 0.6918 | pathogenic | -1.098 | Destabilizing | 0.356 | N | 0.487 | neutral | None | None | None | None | N |
| I/D | 0.9168 | likely_pathogenic | 0.9459 | pathogenic | -2.499 | Highly Destabilizing | 0.038 | N | 0.465 | neutral | None | None | None | None | N |
| I/E | 0.7861 | likely_pathogenic | 0.8357 | pathogenic | -2.237 | Highly Destabilizing | 0.072 | N | 0.483 | neutral | None | None | None | None | N |
| I/F | 0.3373 | likely_benign | 0.3985 | ambiguous | -1.227 | Destabilizing | 0.295 | N | 0.477 | neutral | N | 0.48719588 | None | None | N |
| I/G | 0.809 | likely_pathogenic | 0.8536 | pathogenic | -2.696 | Highly Destabilizing | 0.016 | N | 0.436 | neutral | None | None | None | None | N |
| I/H | 0.737 | likely_pathogenic | 0.7946 | pathogenic | -2.284 | Highly Destabilizing | 0.356 | N | 0.555 | neutral | None | None | None | None | N |
| I/K | 0.6844 | likely_pathogenic | 0.7342 | pathogenic | -1.471 | Destabilizing | 0.072 | N | 0.485 | neutral | None | None | None | None | N |
| I/L | 0.1185 | likely_benign | 0.1314 | benign | -0.521 | Destabilizing | 0.005 | N | 0.245 | neutral | N | 0.43234268 | None | None | N |
| I/M | 0.1269 | likely_benign | 0.1409 | benign | -0.407 | Destabilizing | 0.295 | N | 0.499 | neutral | N | 0.51170754 | None | None | N |
| I/N | 0.4384 | ambiguous | 0.514 | ambiguous | -1.915 | Destabilizing | None | N | 0.444 | neutral | N | 0.4819019 | None | None | N |
| I/P | 0.9473 | likely_pathogenic | 0.9591 | pathogenic | -1.044 | Destabilizing | 0.356 | N | 0.569 | neutral | None | None | None | None | N |
| I/Q | 0.5959 | likely_pathogenic | 0.6612 | pathogenic | -1.701 | Destabilizing | 0.356 | N | 0.566 | neutral | None | None | None | None | N |
| I/R | 0.5999 | likely_pathogenic | 0.6641 | pathogenic | -1.387 | Destabilizing | 0.214 | N | 0.565 | neutral | None | None | None | None | N |
| I/S | 0.4625 | ambiguous | 0.5247 | ambiguous | -2.551 | Highly Destabilizing | 0.001 | N | 0.345 | neutral | N | 0.41125256 | None | None | N |
| I/T | 0.4042 | ambiguous | 0.4466 | ambiguous | -2.143 | Highly Destabilizing | None | N | 0.219 | neutral | N | 0.42700866 | None | None | N |
| I/V | 0.0877 | likely_benign | 0.0963 | benign | -1.044 | Destabilizing | 0.005 | N | 0.255 | neutral | N | 0.39261085 | None | None | N |
| I/W | 0.8847 | likely_pathogenic | 0.9135 | pathogenic | -1.689 | Destabilizing | 0.864 | D | 0.585 | neutral | None | None | None | None | N |
| I/Y | 0.7454 | likely_pathogenic | 0.8011 | pathogenic | -1.315 | Destabilizing | 0.356 | N | 0.519 | 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.