Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32847 | 98764;98765;98766 | chr2:178539526;178539525;178539524 | chr2:179404253;179404252;179404251 |
| N2AB | 31206 | 93841;93842;93843 | chr2:178539526;178539525;178539524 | chr2:179404253;179404252;179404251 |
| N2A | 30279 | 91060;91061;91062 | chr2:178539526;178539525;178539524 | chr2:179404253;179404252;179404251 |
| N2B | 23782 | 71569;71570;71571 | chr2:178539526;178539525;178539524 | chr2:179404253;179404252;179404251 |
| Novex-1 | 23907 | 71944;71945;71946 | chr2:178539526;178539525;178539524 | chr2:179404253;179404252;179404251 |
| Novex-2 | 23974 | 72145;72146;72147 | chr2:178539526;178539525;178539524 | chr2:179404253;179404252;179404251 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | None | None | 1.0 | N | 0.715 | 0.346 | 0.351614576976 | gnomAD-4.0.0 | 1.59117E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85825E-06 | 0 | 0 |
| D/Y | rs776728106  |
0.471 | 1.0 | N | 0.787 | 0.468 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.66E-05 | 0 |
| D/Y | rs776728106 |
0.471 | 1.0 | N | 0.787 | 0.468 | None | gnomAD-4.0.0 | 6.36468E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.1433E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.6312 | likely_pathogenic | 0.5069 | ambiguous | -0.533 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.438153936 | None | None | N |
| D/C | 0.9342 | likely_pathogenic | 0.8856 | pathogenic | -0.15 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| D/E | 0.6697 | likely_pathogenic | 0.5627 | ambiguous | -0.505 | Destabilizing | 1.0 | D | 0.525 | neutral | N | 0.445810627 | None | None | N |
| D/F | 0.9617 | likely_pathogenic | 0.9362 | pathogenic | -0.085 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| D/G | 0.7283 | likely_pathogenic | 0.5901 | pathogenic | -0.856 | Destabilizing | 1.0 | D | 0.74 | deleterious | N | 0.454027465 | None | None | N |
| D/H | 0.8346 | likely_pathogenic | 0.7361 | pathogenic | -0.245 | Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.480616634 | None | None | N |
| D/I | 0.948 | likely_pathogenic | 0.9113 | pathogenic | 0.311 | Stabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| D/K | 0.9426 | likely_pathogenic | 0.9008 | pathogenic | 0.009 | Stabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| D/L | 0.9194 | likely_pathogenic | 0.8728 | pathogenic | 0.311 | Stabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| D/M | 0.9788 | likely_pathogenic | 0.9614 | pathogenic | 0.626 | Stabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| D/N | 0.4801 | ambiguous | 0.3465 | ambiguous | -0.548 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.432763972 | None | None | N |
| D/P | 0.9877 | likely_pathogenic | 0.9821 | pathogenic | 0.054 | Stabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| D/Q | 0.8928 | likely_pathogenic | 0.8267 | pathogenic | -0.423 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| D/R | 0.9236 | likely_pathogenic | 0.8785 | pathogenic | 0.18 | Stabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| D/S | 0.4744 | ambiguous | 0.343 | ambiguous | -0.726 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| D/T | 0.8094 | likely_pathogenic | 0.7092 | pathogenic | -0.451 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | N |
| D/V | 0.8433 | likely_pathogenic | 0.7555 | pathogenic | 0.054 | Stabilizing | 1.0 | D | 0.793 | deleterious | N | 0.455584903 | None | None | N |
| D/W | 0.991 | likely_pathogenic | 0.9855 | pathogenic | 0.166 | Stabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| D/Y | 0.7863 | likely_pathogenic | 0.6799 | pathogenic | 0.191 | Stabilizing | 1.0 | D | 0.787 | deleterious | N | 0.460934795 | 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.