Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2809 | 8650;8651;8652 | chr2:178770276;178770275;178770274 | chr2:179635003;179635002;179635001 |
| N2AB | 2809 | 8650;8651;8652 | chr2:178770276;178770275;178770274 | chr2:179635003;179635002;179635001 |
| N2A | 2809 | 8650;8651;8652 | chr2:178770276;178770275;178770274 | chr2:179635003;179635002;179635001 |
| N2B | 2763 | 8512;8513;8514 | chr2:178770276;178770275;178770274 | chr2:179635003;179635002;179635001 |
| Novex-1 | 2763 | 8512;8513;8514 | chr2:178770276;178770275;178770274 | chr2:179635003;179635002;179635001 |
| Novex-2 | 2763 | 8512;8513;8514 | chr2:178770276;178770275;178770274 | chr2:179635003;179635002;179635001 |
| Novex-3 | 2809 | 8650;8651;8652 | chr2:178770276;178770275;178770274 | chr2:179635003;179635002;179635001 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | rs762595856  |
0.287 | 0.979 | N | 0.365 | 0.333 | 0.191931220699 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.44E-05 | None | 0 | None | 0 | 0 | 0 |
| N/K | rs762595856 |
0.287 | 0.979 | N | 0.365 | 0.333 | 0.191931220699 | gnomAD-4.0.0 | 1.59048E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.773E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3988 | ambiguous | 0.5145 | ambiguous | -0.302 | Destabilizing | 0.984 | D | 0.547 | neutral | None | None | None | None | N |
| N/C | 0.5167 | ambiguous | 0.616 | pathogenic | 0.393 | Stabilizing | 1.0 | D | 0.611 | neutral | None | None | None | None | N |
| N/D | 0.1432 | likely_benign | 0.1674 | benign | -0.016 | Destabilizing | 0.03 | N | 0.267 | neutral | N | 0.483335599 | None | None | N |
| N/E | 0.474 | ambiguous | 0.5817 | pathogenic | -0.072 | Destabilizing | 0.864 | D | 0.388 | neutral | None | None | None | None | N |
| N/F | 0.6683 | likely_pathogenic | 0.7513 | pathogenic | -0.764 | Destabilizing | 0.995 | D | 0.596 | neutral | None | None | None | None | N |
| N/G | 0.2642 | likely_benign | 0.3048 | benign | -0.44 | Destabilizing | 0.963 | D | 0.387 | neutral | None | None | None | None | N |
| N/H | 0.1421 | likely_benign | 0.1845 | benign | -0.513 | Destabilizing | 0.144 | N | 0.334 | neutral | D | 0.536340019 | None | None | N |
| N/I | 0.6012 | likely_pathogenic | 0.6993 | pathogenic | -0.03 | Destabilizing | 0.998 | D | 0.597 | neutral | D | 0.536518583 | None | None | N |
| N/K | 0.3362 | likely_benign | 0.4574 | ambiguous | 0.166 | Stabilizing | 0.979 | D | 0.365 | neutral | N | 0.466558831 | None | None | N |
| N/L | 0.4669 | ambiguous | 0.5776 | pathogenic | -0.03 | Destabilizing | 0.995 | D | 0.596 | neutral | None | None | None | None | N |
| N/M | 0.4689 | ambiguous | 0.5694 | pathogenic | 0.4 | Stabilizing | 1.0 | D | 0.572 | neutral | None | None | None | None | N |
| N/P | 0.9442 | likely_pathogenic | 0.9684 | pathogenic | -0.096 | Destabilizing | 0.999 | D | 0.563 | neutral | None | None | None | None | N |
| N/Q | 0.412 | ambiguous | 0.5344 | ambiguous | -0.303 | Destabilizing | 0.995 | D | 0.42 | neutral | None | None | None | None | N |
| N/R | 0.4576 | ambiguous | 0.5843 | pathogenic | 0.271 | Stabilizing | 0.995 | D | 0.417 | neutral | None | None | None | None | N |
| N/S | 0.1438 | likely_benign | 0.1779 | benign | -0.014 | Destabilizing | 0.906 | D | 0.396 | neutral | N | 0.494574846 | None | None | N |
| N/T | 0.2435 | likely_benign | 0.3529 | ambiguous | 0.057 | Stabilizing | 0.979 | D | 0.369 | neutral | N | 0.472010344 | None | None | N |
| N/V | 0.5878 | likely_pathogenic | 0.6908 | pathogenic | -0.096 | Destabilizing | 0.999 | D | 0.584 | neutral | None | None | None | None | N |
| N/W | 0.8699 | likely_pathogenic | 0.9051 | pathogenic | -0.771 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | N |
| N/Y | 0.2151 | likely_benign | 0.2502 | benign | -0.494 | Destabilizing | 0.988 | D | 0.569 | neutral | N | 0.512415964 | 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.