Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28852 | 86779;86780;86781 | chr2:178559578;178559577;178559576 | chr2:179424305;179424304;179424303 |
| N2AB | 27211 | 81856;81857;81858 | chr2:178559578;178559577;178559576 | chr2:179424305;179424304;179424303 |
| N2A | 26284 | 79075;79076;79077 | chr2:178559578;178559577;178559576 | chr2:179424305;179424304;179424303 |
| N2B | 19787 | 59584;59585;59586 | chr2:178559578;178559577;178559576 | chr2:179424305;179424304;179424303 |
| Novex-1 | 19912 | 59959;59960;59961 | chr2:178559578;178559577;178559576 | chr2:179424305;179424304;179424303 |
| Novex-2 | 19979 | 60160;60161;60162 | chr2:178559578;178559577;178559576 | chr2:179424305;179424304;179424303 |
| 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 | rs1294040369  |
-2.608 | 0.549 | N | 0.711 | 0.297 | 0.548737595723 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/T | rs1294040369 |
-2.608 | 0.549 | N | 0.711 | 0.297 | 0.548737595723 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs1294040369 |
-2.608 | 0.549 | N | 0.711 | 0.297 | 0.548737595723 | gnomAD-4.0.0 | 2.47872E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54284E-06 | 0 | 1.60102E-05 |
| I/V | rs1559277983 |
None | 0.001 | N | 0.193 | 0.051 | 0.242244723065 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6175 | likely_pathogenic | 0.6197 | pathogenic | -2.253 | Highly Destabilizing | 0.25 | N | 0.646 | neutral | None | None | None | None | N |
| I/C | 0.6548 | likely_pathogenic | 0.669 | pathogenic | -1.701 | Destabilizing | 0.977 | D | 0.691 | prob.neutral | None | None | None | None | N |
| I/D | 0.9739 | likely_pathogenic | 0.9715 | pathogenic | -2.107 | Highly Destabilizing | 0.972 | D | 0.803 | deleterious | None | None | None | None | N |
| I/E | 0.9592 | likely_pathogenic | 0.9554 | pathogenic | -1.999 | Destabilizing | 0.92 | D | 0.789 | deleterious | None | None | None | None | N |
| I/F | 0.2236 | likely_benign | 0.2117 | benign | -1.541 | Destabilizing | 0.81 | D | 0.741 | deleterious | N | 0.492121707 | None | None | N |
| I/G | 0.8821 | likely_pathogenic | 0.8794 | pathogenic | -2.699 | Highly Destabilizing | 0.92 | D | 0.787 | deleterious | None | None | None | None | N |
| I/H | 0.908 | likely_pathogenic | 0.9043 | pathogenic | -2.071 | Highly Destabilizing | 0.992 | D | 0.768 | deleterious | None | None | None | None | N |
| I/K | 0.9076 | likely_pathogenic | 0.9014 | pathogenic | -1.583 | Destabilizing | 0.92 | D | 0.792 | deleterious | None | None | None | None | N |
| I/L | 0.0905 | likely_benign | 0.0858 | benign | -1.023 | Destabilizing | 0.002 | N | 0.257 | neutral | N | 0.360202079 | None | None | N |
| I/M | 0.1202 | likely_benign | 0.1189 | benign | -0.939 | Destabilizing | 0.81 | D | 0.669 | neutral | N | 0.499549111 | None | None | N |
| I/N | 0.782 | likely_pathogenic | 0.7842 | pathogenic | -1.618 | Destabilizing | 0.963 | D | 0.803 | deleterious | N | 0.483676596 | None | None | N |
| I/P | 0.8237 | likely_pathogenic | 0.8283 | pathogenic | -1.407 | Destabilizing | 0.972 | D | 0.804 | deleterious | None | None | None | None | N |
| I/Q | 0.9039 | likely_pathogenic | 0.8982 | pathogenic | -1.669 | Destabilizing | 0.972 | D | 0.797 | deleterious | None | None | None | None | N |
| I/R | 0.8804 | likely_pathogenic | 0.8692 | pathogenic | -1.161 | Destabilizing | 0.92 | D | 0.803 | deleterious | None | None | None | None | N |
| I/S | 0.7587 | likely_pathogenic | 0.7565 | pathogenic | -2.33 | Highly Destabilizing | 0.81 | D | 0.757 | deleterious | D | 0.522964689 | None | None | N |
| I/T | 0.5674 | likely_pathogenic | 0.581 | pathogenic | -2.087 | Highly Destabilizing | 0.549 | D | 0.711 | prob.delet. | N | 0.471813312 | None | None | N |
| I/V | 0.0682 | likely_benign | 0.0689 | benign | -1.407 | Destabilizing | 0.001 | N | 0.193 | neutral | N | 0.405267939 | None | None | N |
| I/W | 0.9099 | likely_pathogenic | 0.9036 | pathogenic | -1.759 | Destabilizing | 0.992 | D | 0.78 | deleterious | None | None | None | None | N |
| I/Y | 0.7549 | likely_pathogenic | 0.7401 | pathogenic | -1.496 | Destabilizing | 0.92 | D | 0.755 | 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.