Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32464 | 97615;97616;97617 | chr2:178542366;178542365;178542364 | chr2:179407093;179407092;179407091 |
| N2AB | 30823 | 92692;92693;92694 | chr2:178542366;178542365;178542364 | chr2:179407093;179407092;179407091 |
| N2A | 29896 | 89911;89912;89913 | chr2:178542366;178542365;178542364 | chr2:179407093;179407092;179407091 |
| N2B | 23399 | 70420;70421;70422 | chr2:178542366;178542365;178542364 | chr2:179407093;179407092;179407091 |
| Novex-1 | 23524 | 70795;70796;70797 | chr2:178542366;178542365;178542364 | chr2:179407093;179407092;179407091 |
| Novex-2 | 23591 | 70996;70997;70998 | chr2:178542366;178542365;178542364 | chr2:179407093;179407092;179407091 |
| 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/R | rs756216070  |
-1.324 | 1.0 | D | 0.815 | 0.857 | 0.937250231728 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| L/R | rs756216070 |
-1.324 | 1.0 | D | 0.815 | 0.857 | 0.937250231728 | gnomAD-4.0.0 | 2.73711E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.63768E-05 | 0 |
| L/V | None | None | 0.999 | D | 0.818 | 0.602 | 0.832539624572 | gnomAD-4.0.0 | 1.59163E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85879E-06 | 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 | 0.9584 | likely_pathogenic | 0.9419 | pathogenic | -2.537 | Highly Destabilizing | 0.999 | D | 0.801 | deleterious | None | None | None | None | N |
| L/C | 0.9173 | likely_pathogenic | 0.8818 | pathogenic | -2.179 | Highly Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| L/D | 0.9991 | likely_pathogenic | 0.9988 | pathogenic | -2.507 | Highly Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | N |
| L/E | 0.995 | likely_pathogenic | 0.9928 | pathogenic | -2.368 | Highly Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| L/F | 0.863 | likely_pathogenic | 0.7793 | pathogenic | -1.769 | Destabilizing | 1.0 | D | 0.854 | deleterious | D | 0.655457491 | None | None | N |
| L/G | 0.9896 | likely_pathogenic | 0.9862 | pathogenic | -3.014 | Highly Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| L/H | 0.9853 | likely_pathogenic | 0.979 | pathogenic | -2.242 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | D | 0.68180282 | None | None | N |
| L/I | 0.4428 | ambiguous | 0.3738 | ambiguous | -1.196 | Destabilizing | 0.999 | D | 0.817 | deleterious | D | 0.638429109 | None | None | N |
| L/K | 0.9867 | likely_pathogenic | 0.9837 | pathogenic | -1.817 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| L/M | 0.4466 | ambiguous | 0.3728 | ambiguous | -1.17 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| L/N | 0.9879 | likely_pathogenic | 0.9857 | pathogenic | -1.976 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| L/P | 0.9907 | likely_pathogenic | 0.985 | pathogenic | -1.62 | Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.68180282 | None | None | N |
| L/Q | 0.9748 | likely_pathogenic | 0.9639 | pathogenic | -2.011 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| L/R | 0.9804 | likely_pathogenic | 0.9717 | pathogenic | -1.33 | Destabilizing | 1.0 | D | 0.815 | deleterious | D | 0.68180282 | None | None | N |
| L/S | 0.9936 | likely_pathogenic | 0.9903 | pathogenic | -2.748 | Highly Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| L/T | 0.9648 | likely_pathogenic | 0.9522 | pathogenic | -2.463 | Highly Destabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | N |
| L/V | 0.5233 | ambiguous | 0.4408 | ambiguous | -1.62 | Destabilizing | 0.999 | D | 0.818 | deleterious | D | 0.602554311 | None | None | N |
| L/W | 0.9863 | likely_pathogenic | 0.9748 | pathogenic | -1.965 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| L/Y | 0.9843 | likely_pathogenic | 0.9755 | pathogenic | -1.734 | Destabilizing | 1.0 | D | 0.795 | 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.