Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15540 | 46843;46844;46845 | chr2:178619699;178619698;178619697 | chr2:179484426;179484425;179484424 |
| N2AB | 13899 | 41920;41921;41922 | chr2:178619699;178619698;178619697 | chr2:179484426;179484425;179484424 |
| N2A | 12972 | 39139;39140;39141 | chr2:178619699;178619698;178619697 | chr2:179484426;179484425;179484424 |
| N2B | 6475 | 19648;19649;19650 | chr2:178619699;178619698;178619697 | chr2:179484426;179484425;179484424 |
| Novex-1 | 6600 | 20023;20024;20025 | chr2:178619699;178619698;178619697 | chr2:179484426;179484425;179484424 |
| Novex-2 | 6667 | 20224;20225;20226 | chr2:178619699;178619698;178619697 | chr2:179484426;179484425;179484424 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs1184454225  |
None | 0.124 | N | 0.481 | 0.465 | 0.339555952218 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/G | rs1184454225 |
None | 0.124 | N | 0.481 | 0.465 | 0.339555952218 | gnomAD-4.0.0 | 2.567E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.79609E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2765 | likely_benign | 0.3781 | ambiguous | -0.323 | Destabilizing | 0.22 | N | 0.527 | neutral | N | 0.514128034 | None | None | N |
| D/C | 0.725 | likely_pathogenic | 0.874 | pathogenic | -0.018 | Destabilizing | 0.968 | D | 0.737 | prob.delet. | None | None | None | None | N |
| D/E | 0.1723 | likely_benign | 0.2107 | benign | -0.604 | Destabilizing | None | N | 0.097 | neutral | N | 0.455742706 | None | None | N |
| D/F | 0.7469 | likely_pathogenic | 0.8665 | pathogenic | -0.412 | Destabilizing | 0.89 | D | 0.661 | neutral | None | None | None | None | N |
| D/G | 0.2294 | likely_benign | 0.3303 | benign | -0.583 | Destabilizing | 0.124 | N | 0.481 | neutral | N | 0.485629562 | None | None | N |
| D/H | 0.3849 | ambiguous | 0.5302 | ambiguous | -0.718 | Destabilizing | 0.497 | N | 0.549 | neutral | D | 0.525070789 | None | None | N |
| D/I | 0.6661 | likely_pathogenic | 0.8106 | pathogenic | 0.326 | Stabilizing | 0.726 | D | 0.661 | neutral | None | None | None | None | N |
| D/K | 0.5002 | ambiguous | 0.6117 | pathogenic | -0.299 | Destabilizing | 0.157 | N | 0.478 | neutral | None | None | None | None | N |
| D/L | 0.5809 | likely_pathogenic | 0.7239 | pathogenic | 0.326 | Stabilizing | 0.567 | D | 0.613 | neutral | None | None | None | None | N |
| D/M | 0.7549 | likely_pathogenic | 0.8632 | pathogenic | 0.723 | Stabilizing | 0.968 | D | 0.655 | neutral | None | None | None | None | N |
| D/N | 0.1035 | likely_benign | 0.1425 | benign | -0.471 | Destabilizing | 0.001 | N | 0.225 | neutral | N | 0.397480749 | None | None | N |
| D/P | 0.8458 | likely_pathogenic | 0.9425 | pathogenic | 0.134 | Stabilizing | 0.726 | D | 0.546 | neutral | None | None | None | None | N |
| D/Q | 0.3894 | ambiguous | 0.5078 | ambiguous | -0.399 | Destabilizing | 0.157 | N | 0.475 | neutral | None | None | None | None | N |
| D/R | 0.5203 | ambiguous | 0.6426 | pathogenic | -0.229 | Destabilizing | 0.567 | D | 0.574 | neutral | None | None | None | None | N |
| D/S | 0.166 | likely_benign | 0.2338 | benign | -0.644 | Destabilizing | 0.157 | N | 0.436 | neutral | None | None | None | None | N |
| D/T | 0.408 | ambiguous | 0.5532 | ambiguous | -0.454 | Destabilizing | 0.157 | N | 0.517 | neutral | None | None | None | None | N |
| D/V | 0.4768 | ambiguous | 0.6305 | pathogenic | 0.134 | Stabilizing | 0.667 | D | 0.613 | neutral | D | 0.540374944 | None | None | N |
| D/W | 0.9227 | likely_pathogenic | 0.9725 | pathogenic | -0.4 | Destabilizing | 0.968 | D | 0.751 | deleterious | None | None | None | None | N |
| D/Y | 0.3806 | ambiguous | 0.5492 | ambiguous | -0.242 | Destabilizing | 0.859 | D | 0.663 | neutral | D | 0.540374944 | 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.