Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35156 | 105691;105692;105693 | chr2:178531149;178531148;178531147 | chr2:179395876;179395875;179395874 |
| N2AB | 33515 | 100768;100769;100770 | chr2:178531149;178531148;178531147 | chr2:179395876;179395875;179395874 |
| N2A | 32588 | 97987;97988;97989 | chr2:178531149;178531148;178531147 | chr2:179395876;179395875;179395874 |
| N2B | 26091 | 78496;78497;78498 | chr2:178531149;178531148;178531147 | chr2:179395876;179395875;179395874 |
| Novex-1 | 26216 | 78871;78872;78873 | chr2:178531149;178531148;178531147 | chr2:179395876;179395875;179395874 |
| Novex-2 | 26283 | 79072;79073;79074 | chr2:178531149;178531148;178531147 | chr2:179395876;179395875;179395874 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs538363206  |
0.254 | 1.0 | D | 0.744 | 0.686 | 0.88459850544 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.54E-05 | 0 |
| P/L | rs538363206 |
0.254 | 1.0 | D | 0.744 | 0.686 | 0.88459850544 | gnomAD-4.0.0 | 9.5779E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29575E-06 | 4.63725E-05 | 4.96903E-05 |
| P/R | rs538363206 |
0.388 | 1.0 | D | 0.761 | 0.703 | 0.80067929644 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.66908E-04 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/R | rs538363206 |
0.388 | 1.0 | D | 0.761 | 0.703 | 0.80067929644 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 3.84911E-04 | None | 0 | 0 | 0 | 0 | 0 |
| P/R | rs538363206 |
0.388 | 1.0 | D | 0.761 | 0.703 | 0.80067929644 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| P/R | rs538363206 |
0.388 | 1.0 | D | 0.761 | 0.703 | 0.80067929644 | gnomAD-4.0.0 | 4.33723E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.11398E-04 | None | 0 | 0 | 0 | 0 | 3.20061E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.6688 | likely_pathogenic | 0.7976 | pathogenic | -0.855 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | D | 0.560962138 | None | None | I |
| P/C | 0.9832 | likely_pathogenic | 0.9922 | pathogenic | -0.614 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | I |
| P/D | 0.9236 | likely_pathogenic | 0.9605 | pathogenic | -0.732 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| P/E | 0.8894 | likely_pathogenic | 0.9468 | pathogenic | -0.852 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| P/F | 0.9838 | likely_pathogenic | 0.9928 | pathogenic | -1.07 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | I |
| P/G | 0.9166 | likely_pathogenic | 0.9529 | pathogenic | -1.01 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| P/H | 0.9295 | likely_pathogenic | 0.9641 | pathogenic | -0.582 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| P/I | 0.9091 | likely_pathogenic | 0.9404 | pathogenic | -0.589 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | I |
| P/K | 0.9321 | likely_pathogenic | 0.965 | pathogenic | -0.68 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| P/L | 0.7704 | likely_pathogenic | 0.865 | pathogenic | -0.589 | Destabilizing | 1.0 | D | 0.744 | deleterious | D | 0.652407246 | None | None | I |
| P/M | 0.9134 | likely_pathogenic | 0.9544 | pathogenic | -0.369 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | I |
| P/N | 0.9295 | likely_pathogenic | 0.9554 | pathogenic | -0.341 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| P/Q | 0.8877 | likely_pathogenic | 0.9484 | pathogenic | -0.661 | Destabilizing | 1.0 | D | 0.753 | deleterious | D | 0.572483027 | None | None | I |
| P/R | 0.8823 | likely_pathogenic | 0.939 | pathogenic | -0.062 | Destabilizing | 1.0 | D | 0.761 | deleterious | D | 0.652003637 | None | None | I |
| P/S | 0.8723 | likely_pathogenic | 0.9312 | pathogenic | -0.699 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | D | 0.553871793 | None | None | I |
| P/T | 0.7236 | likely_pathogenic | 0.833 | pathogenic | -0.727 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | D | 0.635984276 | None | None | I |
| P/V | 0.8177 | likely_pathogenic | 0.8795 | pathogenic | -0.643 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| P/W | 0.9917 | likely_pathogenic | 0.9962 | pathogenic | -1.12 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | I |
| P/Y | 0.9736 | likely_pathogenic | 0.9866 | pathogenic | -0.842 | Destabilizing | 1.0 | D | 0.801 | 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.