Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15568 | 46927;46928;46929 | chr2:178618848;178618847;178618846 | chr2:179483575;179483574;179483573 |
| N2AB | 13927 | 42004;42005;42006 | chr2:178618848;178618847;178618846 | chr2:179483575;179483574;179483573 |
| N2A | 13000 | 39223;39224;39225 | chr2:178618848;178618847;178618846 | chr2:179483575;179483574;179483573 |
| N2B | 6503 | 19732;19733;19734 | chr2:178618848;178618847;178618846 | chr2:179483575;179483574;179483573 |
| Novex-1 | 6628 | 20107;20108;20109 | chr2:178618848;178618847;178618846 | chr2:179483575;179483574;179483573 |
| Novex-2 | 6695 | 20308;20309;20310 | chr2:178618848;178618847;178618846 | chr2:179483575;179483574;179483573 |
| 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/Q | None | None | 1.0 | D | 0.88 | 0.673 | 0.598035270499 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| P/S | rs561728671  |
-2.131 | 1.0 | D | 0.89 | 0.667 | 0.569173210356 | gnomAD-2.1.1 | 3.26E-05 | None | None | None | None | N | None | 0 | 8.81E-05 | None | 0 | 0 | None | 0 | None | 0 | 4.5E-05 | 0 |
| P/S | rs561728671 |
-2.131 | 1.0 | D | 0.89 | 0.667 | 0.569173210356 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 1.3132E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs561728671 |
-2.131 | 1.0 | D | 0.89 | 0.667 | 0.569173210356 | gnomAD-4.0.0 | 4.22716E-05 | None | None | None | None | N | None | 0 | 1.50946E-04 | None | 0 | 0 | None | 0 | 0 | 4.83776E-05 | 0 | 3.21802E-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 | 0.6145 | likely_pathogenic | 0.6475 | pathogenic | -1.846 | Destabilizing | 1.0 | D | 0.827 | deleterious | D | 0.543188404 | None | None | N |
| P/C | 0.9647 | likely_pathogenic | 0.9694 | pathogenic | -1.416 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| P/D | 0.9982 | likely_pathogenic | 0.9972 | pathogenic | -1.978 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| P/E | 0.9938 | likely_pathogenic | 0.9913 | pathogenic | -1.906 | Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| P/F | 0.9976 | likely_pathogenic | 0.9971 | pathogenic | -1.315 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| P/G | 0.9565 | likely_pathogenic | 0.9567 | pathogenic | -2.249 | Highly Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| P/H | 0.9944 | likely_pathogenic | 0.9937 | pathogenic | -1.816 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| P/I | 0.9539 | likely_pathogenic | 0.9451 | pathogenic | -0.796 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| P/K | 0.9959 | likely_pathogenic | 0.9939 | pathogenic | -1.495 | Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| P/L | 0.8909 | likely_pathogenic | 0.8924 | pathogenic | -0.796 | Destabilizing | 1.0 | D | 0.881 | deleterious | D | 0.543251496 | None | None | N |
| P/M | 0.9814 | likely_pathogenic | 0.9803 | pathogenic | -0.716 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| P/N | 0.9958 | likely_pathogenic | 0.9942 | pathogenic | -1.447 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| P/Q | 0.9866 | likely_pathogenic | 0.984 | pathogenic | -1.539 | Destabilizing | 1.0 | D | 0.88 | deleterious | D | 0.542972417 | None | None | N |
| P/R | 0.9875 | likely_pathogenic | 0.984 | pathogenic | -1.061 | Destabilizing | 1.0 | D | 0.883 | deleterious | D | 0.542972417 | None | None | N |
| P/S | 0.9383 | likely_pathogenic | 0.9408 | pathogenic | -2.037 | Highly Destabilizing | 1.0 | D | 0.89 | deleterious | D | 0.54336457 | None | None | N |
| P/T | 0.9142 | likely_pathogenic | 0.9057 | pathogenic | -1.845 | Destabilizing | 1.0 | D | 0.886 | deleterious | D | 0.543251496 | None | None | N |
| P/V | 0.8571 | likely_pathogenic | 0.8491 | pathogenic | -1.114 | Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| P/W | 0.9993 | likely_pathogenic | 0.9993 | pathogenic | -1.605 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| P/Y | 0.9984 | likely_pathogenic | 0.998 | pathogenic | -1.287 | Destabilizing | 1.0 | D | 0.885 | 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.