Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27402 | 82429;82430;82431 | chr2:178563928;178563927;178563926 | chr2:179428655;179428654;179428653 |
| N2AB | 25761 | 77506;77507;77508 | chr2:178563928;178563927;178563926 | chr2:179428655;179428654;179428653 |
| N2A | 24834 | 74725;74726;74727 | chr2:178563928;178563927;178563926 | chr2:179428655;179428654;179428653 |
| N2B | 18337 | 55234;55235;55236 | chr2:178563928;178563927;178563926 | chr2:179428655;179428654;179428653 |
| Novex-1 | 18462 | 55609;55610;55611 | chr2:178563928;178563927;178563926 | chr2:179428655;179428654;179428653 |
| Novex-2 | 18529 | 55810;55811;55812 | chr2:178563928;178563927;178563926 | chr2:179428655;179428654;179428653 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1440068759  |
-1.979 | 0.967 | N | 0.785 | 0.527 | 0.801486161926 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1440068759 |
-1.979 | 0.967 | N | 0.785 | 0.527 | 0.801486161926 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 1.31113E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78469E-04 |
| I/T | rs1440068759 |
-1.979 | 0.967 | N | 0.785 | 0.527 | 0.801486161926 | gnomAD-4.0.0 | 1.15314E-05 | None | None | None | None | I | None | 1.69153E-05 | 8.47659E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 8.53291E-05 |
| I/V | rs1321218622 |
-1.559 | 0.426 | N | 0.448 | 0.196 | 0.535679682109 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9467 | likely_pathogenic | 0.9469 | pathogenic | -2.345 | Highly Destabilizing | 0.916 | D | 0.691 | prob.neutral | None | None | None | None | I |
| I/C | 0.9478 | likely_pathogenic | 0.9505 | pathogenic | -1.39 | Destabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | I |
| I/D | 0.9956 | likely_pathogenic | 0.996 | pathogenic | -2.402 | Highly Destabilizing | 0.996 | D | 0.837 | deleterious | None | None | None | None | I |
| I/E | 0.992 | likely_pathogenic | 0.9919 | pathogenic | -2.321 | Highly Destabilizing | 0.987 | D | 0.834 | deleterious | None | None | None | None | I |
| I/F | 0.8273 | likely_pathogenic | 0.8496 | pathogenic | -1.643 | Destabilizing | 0.967 | D | 0.749 | deleterious | D | 0.530461852 | None | None | I |
| I/G | 0.9907 | likely_pathogenic | 0.9907 | pathogenic | -2.765 | Highly Destabilizing | 0.987 | D | 0.831 | deleterious | None | None | None | None | I |
| I/H | 0.9867 | likely_pathogenic | 0.9891 | pathogenic | -2.115 | Highly Destabilizing | 0.999 | D | 0.799 | deleterious | None | None | None | None | I |
| I/K | 0.9788 | likely_pathogenic | 0.9796 | pathogenic | -1.764 | Destabilizing | 0.987 | D | 0.831 | deleterious | None | None | None | None | I |
| I/L | 0.3435 | ambiguous | 0.3641 | ambiguous | -1.195 | Destabilizing | 0.011 | N | 0.253 | neutral | N | 0.483871314 | None | None | I |
| I/M | 0.5503 | ambiguous | 0.5667 | pathogenic | -0.816 | Destabilizing | 0.967 | D | 0.721 | prob.delet. | D | 0.532996747 | None | None | I |
| I/N | 0.9355 | likely_pathogenic | 0.936 | pathogenic | -1.714 | Destabilizing | 0.994 | D | 0.836 | deleterious | D | 0.529237765 | None | None | I |
| I/P | 0.9555 | likely_pathogenic | 0.9587 | pathogenic | -1.553 | Destabilizing | 0.996 | D | 0.833 | deleterious | None | None | None | None | I |
| I/Q | 0.9861 | likely_pathogenic | 0.9866 | pathogenic | -1.82 | Destabilizing | 0.996 | D | 0.829 | deleterious | None | None | None | None | I |
| I/R | 0.9671 | likely_pathogenic | 0.9695 | pathogenic | -1.173 | Destabilizing | 0.987 | D | 0.836 | deleterious | None | None | None | None | I |
| I/S | 0.948 | likely_pathogenic | 0.9483 | pathogenic | -2.321 | Highly Destabilizing | 0.983 | D | 0.801 | deleterious | D | 0.539833602 | None | None | I |
| I/T | 0.8762 | likely_pathogenic | 0.8807 | pathogenic | -2.12 | Highly Destabilizing | 0.967 | D | 0.785 | deleterious | N | 0.513335556 | None | None | I |
| I/V | 0.0997 | likely_benign | 0.1033 | benign | -1.553 | Destabilizing | 0.426 | N | 0.448 | neutral | N | 0.47296273 | None | None | I |
| I/W | 0.9957 | likely_pathogenic | 0.9968 | pathogenic | -1.898 | Destabilizing | 0.999 | D | 0.776 | deleterious | None | None | None | None | I |
| I/Y | 0.9696 | likely_pathogenic | 0.9723 | pathogenic | -1.671 | Destabilizing | 0.987 | D | 0.773 | deleterious | None | None | None | None | I |
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.