Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20853 | 62782;62783;62784 | chr2:178589168;178589167;178589166 | chr2:179453895;179453894;179453893 |
| N2AB | 19212 | 57859;57860;57861 | chr2:178589168;178589167;178589166 | chr2:179453895;179453894;179453893 |
| N2A | 18285 | 55078;55079;55080 | chr2:178589168;178589167;178589166 | chr2:179453895;179453894;179453893 |
| N2B | 11788 | 35587;35588;35589 | chr2:178589168;178589167;178589166 | chr2:179453895;179453894;179453893 |
| Novex-1 | 11913 | 35962;35963;35964 | chr2:178589168;178589167;178589166 | chr2:179453895;179453894;179453893 |
| Novex-2 | 11980 | 36163;36164;36165 | chr2:178589168;178589167;178589166 | chr2:179453895;179453894;179453893 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | None | None | 0.999 | N | 0.567 | 0.416 | 0.531342499125 | gnomAD-4.0.0 | 1.59195E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85909E-06 | 0 | 0 |
| F/S | rs375844494  |
-1.58 | 1.0 | N | 0.783 | 0.504 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| F/S | rs375844494 |
-1.58 | 1.0 | N | 0.783 | 0.504 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| F/S | rs375844494 |
-1.58 | 1.0 | N | 0.783 | 0.504 | None | gnomAD-4.0.0 | 1.11568E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.4411E-05 | 0 | 1.60149E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.5919 | likely_pathogenic | 0.6375 | pathogenic | -1.678 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| F/C | 0.3393 | likely_benign | 0.4217 | ambiguous | -0.828 | Destabilizing | 1.0 | D | 0.756 | deleterious | N | 0.411730631 | None | None | I |
| F/D | 0.9072 | likely_pathogenic | 0.9334 | pathogenic | 0.241 | Stabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | I |
| F/E | 0.907 | likely_pathogenic | 0.9302 | pathogenic | 0.279 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| F/G | 0.873 | likely_pathogenic | 0.902 | pathogenic | -1.947 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | I |
| F/H | 0.6782 | likely_pathogenic | 0.7141 | pathogenic | -0.205 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| F/I | 0.4827 | ambiguous | 0.5064 | ambiguous | -0.921 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | N | 0.361283168 | None | None | I |
| F/K | 0.9125 | likely_pathogenic | 0.9209 | pathogenic | -0.728 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | I |
| F/L | 0.9403 | likely_pathogenic | 0.9506 | pathogenic | -0.921 | Destabilizing | 0.999 | D | 0.567 | neutral | N | 0.382311801 | None | None | I |
| F/M | 0.6413 | likely_pathogenic | 0.6702 | pathogenic | -0.763 | Destabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | I |
| F/N | 0.7794 | likely_pathogenic | 0.8308 | pathogenic | -0.726 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | I |
| F/P | 0.9988 | likely_pathogenic | 0.9989 | pathogenic | -1.16 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| F/Q | 0.82 | likely_pathogenic | 0.8433 | pathogenic | -0.787 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | I |
| F/R | 0.8353 | likely_pathogenic | 0.8445 | pathogenic | -0.123 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| F/S | 0.5481 | ambiguous | 0.6177 | pathogenic | -1.532 | Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.35764543 | None | None | I |
| F/T | 0.6215 | likely_pathogenic | 0.6612 | pathogenic | -1.406 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | I |
| F/V | 0.3511 | ambiguous | 0.3769 | ambiguous | -1.16 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.356431921 | None | None | I |
| F/W | 0.737 | likely_pathogenic | 0.7328 | pathogenic | -0.21 | Destabilizing | 1.0 | D | 0.634 | neutral | None | None | None | None | I |
| F/Y | 0.1959 | likely_benign | 0.2129 | benign | -0.372 | Destabilizing | 0.999 | D | 0.563 | neutral | N | 0.415058937 | 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.