Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14865 | 44818;44819;44820 | chr2:178624687;178624686;178624685 | chr2:179489414;179489413;179489412 |
| N2AB | 13224 | 39895;39896;39897 | chr2:178624687;178624686;178624685 | chr2:179489414;179489413;179489412 |
| N2A | 12297 | 37114;37115;37116 | chr2:178624687;178624686;178624685 | chr2:179489414;179489413;179489412 |
| N2B | 5800 | 17623;17624;17625 | chr2:178624687;178624686;178624685 | chr2:179489414;179489413;179489412 |
| Novex-1 | 5925 | 17998;17999;18000 | chr2:178624687;178624686;178624685 | chr2:179489414;179489413;179489412 |
| Novex-2 | 5992 | 18199;18200;18201 | chr2:178624687;178624686;178624685 | chr2:179489414;179489413;179489412 |
| 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/K | rs543102139  |
0.7 | 0.992 | N | 0.63 | 0.372 | 0.322510055762 | gnomAD-2.1.1 | 1.18235E-04 | None | None | None | None | N | None | 0 | 2.27118E-04 | None | 0 | 9.32063E-04 | None | 0 | None | 0 | 5.49E-05 | 0 |
| E/K | rs543102139 |
0.7 | 0.992 | N | 0.63 | 0.372 | 0.322510055762 | gnomAD-3.1.2 | 1.71138E-04 | None | None | None | None | N | None | 0 | 9.85028E-04 | 0 | 0 | 1.16686E-03 | None | 0 | 0 | 7.36E-05 | 0 | 0 |
| E/K | rs543102139 |
0.7 | 0.992 | N | 0.63 | 0.372 | 0.322510055762 | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 3E-03 | 0 | None | None | None | 0 | None |
| E/K | rs543102139 |
0.7 | 0.992 | N | 0.63 | 0.372 | 0.322510055762 | gnomAD-4.0.0 | 5.70574E-05 | None | None | None | None | N | None | 2.66973E-05 | 3.67328E-04 | None | 0 | 5.82072E-04 | None | 0 | 0 | 3.56227E-05 | 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 | 0.2905 | likely_benign | 0.285 | benign | -0.067 | Destabilizing | 0.919 | D | 0.625 | neutral | N | 0.502534838 | None | None | N |
| E/C | 0.9454 | likely_pathogenic | 0.9484 | pathogenic | -0.188 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | N |
| E/D | 0.3381 | likely_benign | 0.3333 | benign | -0.421 | Destabilizing | 0.958 | D | 0.525 | neutral | N | 0.511589718 | None | None | N |
| E/F | 0.8963 | likely_pathogenic | 0.8881 | pathogenic | -0.002 | Destabilizing | 0.995 | D | 0.7 | prob.neutral | None | None | None | None | N |
| E/G | 0.3571 | ambiguous | 0.3311 | benign | -0.214 | Destabilizing | 0.988 | D | 0.61 | neutral | D | 0.560503938 | None | None | N |
| E/H | 0.7876 | likely_pathogenic | 0.7844 | pathogenic | 0.57 | Stabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| E/I | 0.5954 | likely_pathogenic | 0.585 | pathogenic | 0.269 | Stabilizing | 0.991 | D | 0.698 | prob.neutral | None | None | None | None | N |
| E/K | 0.3182 | likely_benign | 0.2963 | benign | 0.483 | Stabilizing | 0.992 | D | 0.63 | neutral | N | 0.467830843 | None | None | N |
| E/L | 0.5804 | likely_pathogenic | 0.5574 | ambiguous | 0.269 | Stabilizing | 0.982 | D | 0.649 | neutral | None | None | None | None | N |
| E/M | 0.6638 | likely_pathogenic | 0.6439 | pathogenic | 0.049 | Stabilizing | 0.999 | D | 0.672 | neutral | None | None | None | None | N |
| E/N | 0.6129 | likely_pathogenic | 0.5942 | pathogenic | 0.063 | Stabilizing | 0.991 | D | 0.649 | neutral | None | None | None | None | N |
| E/P | 0.6881 | likely_pathogenic | 0.688 | pathogenic | 0.176 | Stabilizing | 0.995 | D | 0.659 | neutral | None | None | None | None | N |
| E/Q | 0.2684 | likely_benign | 0.2753 | benign | 0.095 | Stabilizing | 0.998 | D | 0.587 | neutral | N | 0.509603973 | None | None | N |
| E/R | 0.4484 | ambiguous | 0.4547 | ambiguous | 0.749 | Stabilizing | 0.991 | D | 0.666 | neutral | None | None | None | None | N |
| E/S | 0.4411 | ambiguous | 0.4391 | ambiguous | -0.026 | Destabilizing | 0.938 | D | 0.631 | neutral | None | None | None | None | N |
| E/T | 0.4025 | ambiguous | 0.4223 | ambiguous | 0.104 | Stabilizing | 0.086 | N | 0.447 | neutral | None | None | None | None | N |
| E/V | 0.3747 | ambiguous | 0.3569 | ambiguous | 0.176 | Stabilizing | 0.976 | D | 0.603 | neutral | N | 0.503046775 | None | None | N |
| E/W | 0.9659 | likely_pathogenic | 0.9609 | pathogenic | 0.087 | Stabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| E/Y | 0.8673 | likely_pathogenic | 0.847 | pathogenic | 0.236 | Stabilizing | 0.998 | D | 0.683 | prob.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.