Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14374 | 43345;43346;43347 | chr2:178633011;178633010;178633009 | chr2:179497738;179497737;179497736 |
| N2AB | 12733 | 38422;38423;38424 | chr2:178633011;178633010;178633009 | chr2:179497738;179497737;179497736 |
| N2A | 11806 | 35641;35642;35643 | chr2:178633011;178633010;178633009 | chr2:179497738;179497737;179497736 |
| N2B | 5309 | 16150;16151;16152 | chr2:178633011;178633010;178633009 | chr2:179497738;179497737;179497736 |
| Novex-1 | 5434 | 16525;16526;16527 | chr2:178633011;178633010;178633009 | chr2:179497738;179497737;179497736 |
| Novex-2 | 5501 | 16726;16727;16728 | chr2:178633011;178633010;178633009 | chr2:179497738;179497737;179497736 |
| 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/V | rs754227553  |
-1.825 | None | N | 0.249 | 0.041 | 0.139678290688 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 4.46E-05 | 0 |
| I/V | rs754227553 |
-1.825 | None | N | 0.249 | 0.041 | 0.139678290688 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/V | rs754227553 |
-1.825 | None | N | 0.249 | 0.041 | 0.139678290688 | gnomAD-4.0.0 | 2.72783E-05 | None | None | None | None | N | None | 1.33551E-05 | 1.66795E-05 | None | 0 | 0 | None | 0 | 0 | 3.47631E-05 | 0 | 1.60195E-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 | 0.3535 | ambiguous | 0.3038 | benign | -2.768 | Highly Destabilizing | 0.016 | N | 0.514 | neutral | None | None | None | None | N |
| I/C | 0.6314 | likely_pathogenic | 0.6485 | pathogenic | -1.847 | Destabilizing | 0.685 | D | 0.567 | neutral | None | None | None | None | N |
| I/D | 0.7351 | likely_pathogenic | 0.6707 | pathogenic | -3.497 | Highly Destabilizing | 0.221 | N | 0.659 | prob.neutral | None | None | None | None | N |
| I/E | 0.531 | ambiguous | 0.4819 | ambiguous | -3.226 | Highly Destabilizing | 0.075 | N | 0.649 | prob.neutral | None | None | None | None | N |
| I/F | 0.1837 | likely_benign | 0.1705 | benign | -1.729 | Destabilizing | 0.177 | N | 0.551 | neutral | N | 0.407829073 | None | None | N |
| I/G | 0.718 | likely_pathogenic | 0.6636 | pathogenic | -3.318 | Highly Destabilizing | 0.075 | N | 0.628 | neutral | None | None | None | None | N |
| I/H | 0.387 | ambiguous | 0.3688 | ambiguous | -2.919 | Highly Destabilizing | 0.869 | D | 0.705 | prob.delet. | None | None | None | None | N |
| I/K | 0.2656 | likely_benign | 0.2468 | benign | -2.324 | Highly Destabilizing | 0.075 | N | 0.661 | prob.neutral | None | None | None | None | N |
| I/L | 0.159 | likely_benign | 0.1437 | benign | -1.137 | Destabilizing | 0.005 | N | 0.487 | neutral | N | 0.43309025 | None | None | N |
| I/M | 0.1305 | likely_benign | 0.1203 | benign | -1.028 | Destabilizing | 0.177 | N | 0.541 | neutral | N | 0.423567268 | None | None | N |
| I/N | 0.2542 | likely_benign | 0.2266 | benign | -2.844 | Highly Destabilizing | 0.177 | N | 0.648 | neutral | N | 0.425760021 | None | None | N |
| I/P | 0.98 | likely_pathogenic | 0.9684 | pathogenic | -1.669 | Destabilizing | 0.366 | N | 0.649 | prob.neutral | None | None | None | None | N |
| I/Q | 0.3809 | ambiguous | 0.3468 | ambiguous | -2.627 | Highly Destabilizing | 0.366 | N | 0.679 | prob.neutral | None | None | None | None | N |
| I/R | 0.1935 | likely_benign | 0.1848 | benign | -2.083 | Highly Destabilizing | 0.221 | N | 0.673 | prob.neutral | None | None | None | None | N |
| I/S | 0.2371 | likely_benign | 0.2218 | benign | -3.413 | Highly Destabilizing | 0.03 | N | 0.651 | prob.neutral | N | 0.415793249 | None | None | N |
| I/T | 0.1356 | likely_benign | 0.1113 | benign | -3.007 | Highly Destabilizing | None | N | 0.381 | neutral | N | 0.377045541 | None | None | N |
| I/V | 0.0707 | likely_benign | 0.0654 | benign | -1.669 | Destabilizing | None | N | 0.249 | neutral | N | 0.420712714 | None | None | N |
| I/W | 0.8006 | likely_pathogenic | 0.7687 | pathogenic | -2.239 | Highly Destabilizing | 0.869 | D | 0.731 | deleterious | None | None | None | None | N |
| I/Y | 0.4035 | ambiguous | 0.419 | ambiguous | -1.95 | Destabilizing | 0.366 | N | 0.581 | 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.