Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25417 | 76474;76475;76476 | chr2:178569883;178569882;178569881 | chr2:179434610;179434609;179434608 |
| N2AB | 23776 | 71551;71552;71553 | chr2:178569883;178569882;178569881 | chr2:179434610;179434609;179434608 |
| N2A | 22849 | 68770;68771;68772 | chr2:178569883;178569882;178569881 | chr2:179434610;179434609;179434608 |
| N2B | 16352 | 49279;49280;49281 | chr2:178569883;178569882;178569881 | chr2:179434610;179434609;179434608 |
| Novex-1 | 16477 | 49654;49655;49656 | chr2:178569883;178569882;178569881 | chr2:179434610;179434609;179434608 |
| Novex-2 | 16544 | 49855;49856;49857 | chr2:178569883;178569882;178569881 | chr2:179434610;179434609;179434608 |
| 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/L | None | None | 0.002 | N | 0.213 | 0.094 | 0.313818047136 | gnomAD-4.0.0 | 6.84338E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99572E-07 | 0 | 0 |
| I/V | rs755528335  |
-1.225 | None | N | 0.055 | 0.061 | 0.207176502487 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 1.85822E-04 | 0 | 0 |
| I/V | rs755528335 |
-1.225 | None | N | 0.055 | 0.061 | 0.207176502487 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 0 | 0 | 0 |
| I/V | rs755528335 |
-1.225 | None | N | 0.055 | 0.061 | 0.207176502487 | gnomAD-4.0.0 | 3.71896E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.37441E-05 | 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 | 0.1774 | likely_benign | 0.1665 | benign | -2.084 | Highly Destabilizing | 0.007 | N | 0.205 | neutral | None | None | None | None | N |
| I/C | 0.4137 | ambiguous | 0.4087 | ambiguous | -1.602 | Destabilizing | 0.356 | N | 0.34 | neutral | None | None | None | None | N |
| I/D | 0.595 | likely_pathogenic | 0.5383 | ambiguous | -1.803 | Destabilizing | 0.072 | N | 0.441 | neutral | None | None | None | None | N |
| I/E | 0.4549 | ambiguous | 0.4493 | ambiguous | -1.726 | Destabilizing | 0.072 | N | 0.409 | neutral | None | None | None | None | N |
| I/F | 0.1393 | likely_benign | 0.1311 | benign | -1.403 | Destabilizing | 0.072 | N | 0.336 | neutral | None | None | None | None | N |
| I/G | 0.4515 | ambiguous | 0.3949 | ambiguous | -2.482 | Highly Destabilizing | 0.072 | N | 0.417 | neutral | None | None | None | None | N |
| I/H | 0.3386 | likely_benign | 0.3374 | benign | -1.754 | Destabilizing | 0.628 | D | 0.407 | neutral | None | None | None | None | N |
| I/K | 0.1839 | likely_benign | 0.2078 | benign | -1.431 | Destabilizing | None | N | 0.288 | neutral | N | 0.460705509 | None | None | N |
| I/L | 0.1215 | likely_benign | 0.1164 | benign | -1.015 | Destabilizing | 0.002 | N | 0.213 | neutral | N | 0.453374104 | None | None | N |
| I/M | 0.0822 | likely_benign | 0.082 | benign | -1.001 | Destabilizing | 0.171 | N | 0.35 | neutral | N | 0.481158139 | None | None | N |
| I/N | 0.1808 | likely_benign | 0.1613 | benign | -1.4 | Destabilizing | 0.072 | N | 0.463 | neutral | None | None | None | None | N |
| I/P | 0.8679 | likely_pathogenic | 0.8204 | pathogenic | -1.344 | Destabilizing | 0.136 | N | 0.487 | neutral | None | None | None | None | N |
| I/Q | 0.2898 | likely_benign | 0.2995 | benign | -1.509 | Destabilizing | 0.214 | N | 0.525 | neutral | None | None | None | None | N |
| I/R | 0.1632 | likely_benign | 0.1766 | benign | -0.96 | Destabilizing | 0.029 | N | 0.465 | neutral | N | 0.476154964 | None | None | N |
| I/S | 0.1483 | likely_benign | 0.1405 | benign | -2.099 | Highly Destabilizing | 0.016 | N | 0.296 | neutral | None | None | None | None | N |
| I/T | 0.0803 | likely_benign | 0.0807 | benign | -1.897 | Destabilizing | None | N | 0.099 | neutral | N | 0.398771615 | None | None | N |
| I/V | 0.0568 | likely_benign | 0.0536 | benign | -1.344 | Destabilizing | None | N | 0.055 | neutral | N | 0.388013117 | None | None | N |
| I/W | 0.7028 | likely_pathogenic | 0.703 | pathogenic | -1.538 | Destabilizing | 0.864 | D | 0.411 | neutral | None | None | None | None | N |
| I/Y | 0.3808 | ambiguous | 0.3706 | ambiguous | -1.29 | Destabilizing | 0.356 | N | 0.464 | 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.