Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15432 | 46519;46520;46521 | chr2:178620227;178620226;178620225 | chr2:179484954;179484953;179484952 |
| N2AB | 13791 | 41596;41597;41598 | chr2:178620227;178620226;178620225 | chr2:179484954;179484953;179484952 |
| N2A | 12864 | 38815;38816;38817 | chr2:178620227;178620226;178620225 | chr2:179484954;179484953;179484952 |
| N2B | 6367 | 19324;19325;19326 | chr2:178620227;178620226;178620225 | chr2:179484954;179484953;179484952 |
| Novex-1 | 6492 | 19699;19700;19701 | chr2:178620227;178620226;178620225 | chr2:179484954;179484953;179484952 |
| Novex-2 | 6559 | 19900;19901;19902 | chr2:178620227;178620226;178620225 | chr2:179484954;179484953;179484952 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | None | None | 0.008 | N | 0.278 | 0.254 | 0.407632638399 | gnomAD-4.0.0 | 6.49868E-06 | None | None | None | None | N | None | 2.29073E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.40127E-05 | 1.75759E-05 |
| E/D | None | None | 0.008 | N | 0.251 | 0.079 | 0.502568190621 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| E/Q | rs1319118967  |
None | 0.901 | N | 0.465 | 0.202 | 0.559427399277 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/Q | rs1319118967 |
None | 0.901 | N | 0.465 | 0.202 | 0.559427399277 | gnomAD-4.0.0 | 1.95325E-06 | None | None | None | None | N | None | 1.39051E-05 | 2.14298E-05 | None | 0 | 2.27386E-05 | None | 0 | 0 | 0 | 0 | 0 |
| E/V | rs1202126471 |
None | 0.82 | D | 0.482 | 0.372 | 0.636139071576 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/V | rs1202126471 |
None | 0.82 | D | 0.482 | 0.372 | 0.636139071576 | gnomAD-4.0.0 | 1.31626E-05 | None | None | None | None | N | None | 4.82812E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.1868 | likely_benign | 0.1954 | benign | -0.337 | Destabilizing | 0.008 | N | 0.278 | neutral | N | 0.496308456 | None | None | N |
| E/C | 0.9536 | likely_pathogenic | 0.9641 | pathogenic | -0.341 | Destabilizing | 0.996 | D | 0.593 | neutral | None | None | None | None | N |
| E/D | 0.276 | likely_benign | 0.344 | ambiguous | -0.451 | Destabilizing | 0.008 | N | 0.251 | neutral | N | 0.515238233 | None | None | N |
| E/F | 0.9324 | likely_pathogenic | 0.9557 | pathogenic | 0.154 | Stabilizing | 0.987 | D | 0.572 | neutral | None | None | None | None | N |
| E/G | 0.332 | likely_benign | 0.3452 | ambiguous | -0.575 | Destabilizing | 0.008 | N | 0.293 | neutral | D | 0.554895993 | None | None | N |
| E/H | 0.8237 | likely_pathogenic | 0.8526 | pathogenic | 0.625 | Stabilizing | 0.996 | D | 0.453 | neutral | None | None | None | None | N |
| E/I | 0.6344 | likely_pathogenic | 0.7181 | pathogenic | 0.276 | Stabilizing | 0.923 | D | 0.567 | neutral | None | None | None | None | N |
| E/K | 0.3973 | ambiguous | 0.4007 | ambiguous | 0.38 | Stabilizing | 0.722 | D | 0.509 | neutral | N | 0.511494936 | None | None | N |
| E/L | 0.6723 | likely_pathogenic | 0.7452 | pathogenic | 0.276 | Stabilizing | 0.923 | D | 0.505 | neutral | None | None | None | None | N |
| E/M | 0.7077 | likely_pathogenic | 0.7736 | pathogenic | 0.141 | Stabilizing | 0.996 | D | 0.552 | neutral | None | None | None | None | N |
| E/N | 0.5101 | ambiguous | 0.6013 | pathogenic | -0.361 | Destabilizing | 0.858 | D | 0.466 | neutral | None | None | None | None | N |
| E/P | 0.4201 | ambiguous | 0.4456 | ambiguous | 0.092 | Stabilizing | 0.961 | D | 0.514 | neutral | None | None | None | None | N |
| E/Q | 0.2888 | likely_benign | 0.2875 | benign | -0.252 | Destabilizing | 0.901 | D | 0.465 | neutral | N | 0.504027163 | None | None | N |
| E/R | 0.5813 | likely_pathogenic | 0.5789 | pathogenic | 0.766 | Stabilizing | 0.961 | D | 0.464 | neutral | None | None | None | None | N |
| E/S | 0.3592 | ambiguous | 0.3883 | ambiguous | -0.462 | Destabilizing | 0.633 | D | 0.497 | neutral | None | None | None | None | N |
| E/T | 0.4295 | ambiguous | 0.4875 | ambiguous | -0.24 | Destabilizing | 0.775 | D | 0.514 | neutral | None | None | None | None | N |
| E/V | 0.4126 | ambiguous | 0.4726 | ambiguous | 0.092 | Stabilizing | 0.82 | D | 0.482 | neutral | D | 0.554732472 | None | None | N |
| E/W | 0.9779 | likely_pathogenic | 0.9844 | pathogenic | 0.408 | Stabilizing | 0.996 | D | 0.641 | neutral | None | None | None | None | N |
| E/Y | 0.8666 | likely_pathogenic | 0.9089 | pathogenic | 0.434 | Stabilizing | 0.987 | D | 0.545 | 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.