Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19518 | 58777;58778;58779 | chr2:178593748;178593747;178593746 | chr2:179458475;179458474;179458473 |
| N2AB | 17877 | 53854;53855;53856 | chr2:178593748;178593747;178593746 | chr2:179458475;179458474;179458473 |
| N2A | 16950 | 51073;51074;51075 | chr2:178593748;178593747;178593746 | chr2:179458475;179458474;179458473 |
| N2B | 10453 | 31582;31583;31584 | chr2:178593748;178593747;178593746 | chr2:179458475;179458474;179458473 |
| Novex-1 | 10578 | 31957;31958;31959 | chr2:178593748;178593747;178593746 | chr2:179458475;179458474;179458473 |
| Novex-2 | 10645 | 32158;32159;32160 | chr2:178593748;178593747;178593746 | chr2:179458475;179458474;179458473 |
| 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/D | rs747066203  |
-2.09 | 0.999 | N | 0.649 | 0.345 | 0.295974979623 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.62E-05 | None | 0 | None | 0 | 0 | 0 |
| E/D | rs747066203 |
-2.09 | 0.999 | N | 0.649 | 0.345 | 0.295974979623 | gnomAD-4.0.0 | 6.84383E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52755E-05 | None | 0 | 0 | 0 | 0 | 0 |
| E/K | rs1329313961 |
-2.384 | 0.999 | N | 0.686 | 0.377 | 0.489243007833 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| E/K | rs1329313961 |
-2.384 | 0.999 | N | 0.686 | 0.377 | 0.489243007833 | gnomAD-4.0.0 | 1.59227E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43308E-05 | 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 | 0.8361 | likely_pathogenic | 0.7901 | pathogenic | -1.255 | Destabilizing | 0.999 | D | 0.692 | prob.neutral | D | 0.539635202 | None | None | N |
| E/C | 0.9841 | likely_pathogenic | 0.9687 | pathogenic | -0.684 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| E/D | 0.6911 | likely_pathogenic | 0.6494 | pathogenic | -1.691 | Destabilizing | 0.999 | D | 0.649 | neutral | N | 0.481790492 | None | None | N |
| E/F | 0.9863 | likely_pathogenic | 0.9702 | pathogenic | -0.85 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| E/G | 0.8519 | likely_pathogenic | 0.8247 | pathogenic | -1.657 | Destabilizing | 1.0 | D | 0.755 | deleterious | D | 0.523305374 | None | None | N |
| E/H | 0.9497 | likely_pathogenic | 0.9055 | pathogenic | -0.923 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| E/I | 0.9529 | likely_pathogenic | 0.9243 | pathogenic | -0.101 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| E/K | 0.854 | likely_pathogenic | 0.8072 | pathogenic | -1.591 | Destabilizing | 0.999 | D | 0.686 | prob.neutral | N | 0.51549056 | None | None | N |
| E/L | 0.9427 | likely_pathogenic | 0.8931 | pathogenic | -0.101 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| E/M | 0.9347 | likely_pathogenic | 0.88 | pathogenic | 0.602 | Stabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| E/N | 0.9387 | likely_pathogenic | 0.9075 | pathogenic | -1.845 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| E/P | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| E/Q | 0.434 | ambiguous | 0.3493 | ambiguous | -1.504 | Destabilizing | 1.0 | D | 0.755 | deleterious | N | 0.470216696 | None | None | N |
| E/R | 0.8972 | likely_pathogenic | 0.8641 | pathogenic | -1.454 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| E/S | 0.8314 | likely_pathogenic | 0.7645 | pathogenic | -2.437 | Highly Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | N |
| E/T | 0.9114 | likely_pathogenic | 0.871 | pathogenic | -2.066 | Highly Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| E/V | 0.8863 | likely_pathogenic | 0.8363 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.757 | deleterious | N | 0.513897625 | None | None | N |
| E/W | 0.9905 | likely_pathogenic | 0.9797 | pathogenic | -1.007 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| E/Y | 0.9769 | likely_pathogenic | 0.9519 | pathogenic | -0.726 | Destabilizing | 1.0 | D | 0.779 | deleterious | 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.