Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22023 | 66292;66293;66294 | chr2:178582389;178582388;178582387 | chr2:179447116;179447115;179447114 |
| N2AB | 20382 | 61369;61370;61371 | chr2:178582389;178582388;178582387 | chr2:179447116;179447115;179447114 |
| N2A | 19455 | 58588;58589;58590 | chr2:178582389;178582388;178582387 | chr2:179447116;179447115;179447114 |
| N2B | 12958 | 39097;39098;39099 | chr2:178582389;178582388;178582387 | chr2:179447116;179447115;179447114 |
| Novex-1 | 13083 | 39472;39473;39474 | chr2:178582389;178582388;178582387 | chr2:179447116;179447115;179447114 |
| Novex-2 | 13150 | 39673;39674;39675 | chr2:178582389;178582388;178582387 | chr2:179447116;179447115;179447114 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/C | rs1060500452  |
-1.005 | 1.0 | D | 0.847 | 0.673 | 0.781605297421 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66667E-04 |
| G/C | rs1060500452 |
-1.005 | 1.0 | D | 0.847 | 0.673 | 0.781605297421 | gnomAD-4.0.0 | 6.84606E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.998E-07 | 0 | 0 |
| G/R | rs1060500452 |
-1.059 | 1.0 | N | 0.868 | 0.574 | 0.714618863138 | 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 |
| G/R | rs1060500452 |
-1.059 | 1.0 | N | 0.868 | 0.574 | 0.714618863138 | gnomAD-4.0.0 | 3.42303E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.80194E-05 | 0 |
| G/S | None | None | 1.0 | N | 0.803 | 0.448 | 0.457650129517 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| G/S | None | None | 1.0 | N | 0.803 | 0.448 | 0.457650129517 | gnomAD-4.0.0 | 1.86031E-06 | None | None | None | None | N | None | 4.01048E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| G/V | rs1223364333 |
-0.656 | 1.0 | D | 0.853 | 0.569 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| G/V | rs1223364333 |
-0.656 | 1.0 | D | 0.853 | 0.569 | None | gnomAD-4.0.0 | 1.59343E-06 | None | None | None | None | N | None | 5.67086E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.8222 | likely_pathogenic | 0.7769 | pathogenic | -0.65 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.481317328 | None | None | N |
| G/C | 0.8607 | likely_pathogenic | 0.8084 | pathogenic | -0.858 | Destabilizing | 1.0 | D | 0.847 | deleterious | D | 0.546380968 | None | None | N |
| G/D | 0.6114 | likely_pathogenic | 0.5507 | ambiguous | -1.212 | Destabilizing | 1.0 | D | 0.825 | deleterious | D | 0.525855852 | None | None | N |
| G/E | 0.8716 | likely_pathogenic | 0.8305 | pathogenic | -1.32 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| G/F | 0.9733 | likely_pathogenic | 0.9608 | pathogenic | -1.113 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| G/H | 0.9094 | likely_pathogenic | 0.8719 | pathogenic | -1.134 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| G/I | 0.9808 | likely_pathogenic | 0.9721 | pathogenic | -0.477 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| G/K | 0.9485 | likely_pathogenic | 0.927 | pathogenic | -1.352 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| G/L | 0.9658 | likely_pathogenic | 0.9562 | pathogenic | -0.477 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| G/M | 0.9654 | likely_pathogenic | 0.9534 | pathogenic | -0.364 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| G/N | 0.4896 | ambiguous | 0.4384 | ambiguous | -0.939 | Destabilizing | 0.98 | D | 0.643 | neutral | None | None | None | None | N |
| G/P | 0.9986 | likely_pathogenic | 0.9978 | pathogenic | -0.496 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| G/Q | 0.8981 | likely_pathogenic | 0.8677 | pathogenic | -1.195 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| G/R | 0.9343 | likely_pathogenic | 0.9087 | pathogenic | -0.872 | Destabilizing | 1.0 | D | 0.868 | deleterious | N | 0.515488376 | None | None | N |
| G/S | 0.4951 | ambiguous | 0.422 | ambiguous | -1.098 | Destabilizing | 1.0 | D | 0.803 | deleterious | N | 0.507130584 | None | None | N |
| G/T | 0.85 | likely_pathogenic | 0.8045 | pathogenic | -1.142 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| G/V | 0.963 | likely_pathogenic | 0.9509 | pathogenic | -0.496 | Destabilizing | 1.0 | D | 0.853 | deleterious | D | 0.5343531 | None | None | N |
| G/W | 0.9516 | likely_pathogenic | 0.9292 | pathogenic | -1.394 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| G/Y | 0.9293 | likely_pathogenic | 0.8924 | pathogenic | -1.034 | Destabilizing | 1.0 | D | 0.844 | 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.