Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29753 | 89482;89483;89484 | chr2:178553748;178553747;178553746 | chr2:179418475;179418474;179418473 |
| N2AB | 28112 | 84559;84560;84561 | chr2:178553748;178553747;178553746 | chr2:179418475;179418474;179418473 |
| N2A | 27185 | 81778;81779;81780 | chr2:178553748;178553747;178553746 | chr2:179418475;179418474;179418473 |
| N2B | 20688 | 62287;62288;62289 | chr2:178553748;178553747;178553746 | chr2:179418475;179418474;179418473 |
| Novex-1 | 20813 | 62662;62663;62664 | chr2:178553748;178553747;178553746 | chr2:179418475;179418474;179418473 |
| Novex-2 | 20880 | 62863;62864;62865 | chr2:178553748;178553747;178553746 | chr2:179418475;179418474;179418473 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs1700246631  |
None | 1.0 | N | 0.763 | 0.493 | 0.565829876908 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/F | rs1700246631 |
None | 1.0 | N | 0.763 | 0.493 | 0.565829876908 | gnomAD-4.0.0 | 6.57022E-06 | None | None | None | None | N | None | 2.4122E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/H | rs369279892 |
-3.205 | 1.0 | D | 0.912 | 0.795 | None | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 2.58632E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/H | rs369279892 |
-3.205 | 1.0 | D | 0.912 | 0.795 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/H | rs369279892 |
-3.205 | 1.0 | D | 0.912 | 0.795 | None | gnomAD-4.0.0 | 5.14028E-06 | None | None | None | None | N | None | 6.7675E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.7912 | likely_pathogenic | 0.77 | pathogenic | -2.625 | Highly Destabilizing | 0.999 | D | 0.726 | prob.delet. | None | None | None | None | N |
| L/C | 0.8815 | likely_pathogenic | 0.8703 | pathogenic | -1.794 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| L/D | 0.9992 | likely_pathogenic | 0.999 | pathogenic | -3.49 | Highly Destabilizing | 1.0 | D | 0.946 | deleterious | None | None | None | None | N |
| L/E | 0.9938 | likely_pathogenic | 0.9932 | pathogenic | -3.162 | Highly Destabilizing | 1.0 | D | 0.932 | deleterious | None | None | None | None | N |
| L/F | 0.5423 | ambiguous | 0.5149 | ambiguous | -1.648 | Destabilizing | 1.0 | D | 0.763 | deleterious | N | 0.521710256 | None | None | N |
| L/G | 0.9857 | likely_pathogenic | 0.9832 | pathogenic | -3.227 | Highly Destabilizing | 1.0 | D | 0.923 | deleterious | None | None | None | None | N |
| L/H | 0.9885 | likely_pathogenic | 0.9847 | pathogenic | -3.045 | Highly Destabilizing | 1.0 | D | 0.912 | deleterious | D | 0.549475749 | None | None | N |
| L/I | 0.1013 | likely_benign | 0.0945 | benign | -0.807 | Destabilizing | 0.999 | D | 0.55 | neutral | N | 0.503731141 | None | None | N |
| L/K | 0.9887 | likely_pathogenic | 0.9875 | pathogenic | -2.134 | Highly Destabilizing | 1.0 | D | 0.916 | deleterious | None | None | None | None | N |
| L/M | 0.2329 | likely_benign | 0.2352 | benign | -0.946 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| L/N | 0.9955 | likely_pathogenic | 0.9948 | pathogenic | -2.912 | Highly Destabilizing | 1.0 | D | 0.949 | deleterious | None | None | None | None | N |
| L/P | 0.9901 | likely_pathogenic | 0.9874 | pathogenic | -1.405 | Destabilizing | 1.0 | D | 0.949 | deleterious | D | 0.549475749 | None | None | N |
| L/Q | 0.9812 | likely_pathogenic | 0.9783 | pathogenic | -2.524 | Highly Destabilizing | 1.0 | D | 0.943 | deleterious | None | None | None | None | N |
| L/R | 0.9794 | likely_pathogenic | 0.9751 | pathogenic | -2.263 | Highly Destabilizing | 1.0 | D | 0.931 | deleterious | D | 0.549475749 | None | None | N |
| L/S | 0.9823 | likely_pathogenic | 0.9773 | pathogenic | -3.397 | Highly Destabilizing | 1.0 | D | 0.918 | deleterious | None | None | None | None | N |
| L/T | 0.8456 | likely_pathogenic | 0.8297 | pathogenic | -2.902 | Highly Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| L/V | 0.1207 | likely_benign | 0.1044 | benign | -1.405 | Destabilizing | 0.999 | D | 0.565 | neutral | N | 0.521159321 | None | None | N |
| L/W | 0.9489 | likely_pathogenic | 0.932 | pathogenic | -2.077 | Highly Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| L/Y | 0.9601 | likely_pathogenic | 0.9508 | pathogenic | -1.843 | Destabilizing | 1.0 | D | 0.86 | 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.