Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31323 | 94192;94193;94194 | chr2:178547659;178547658;178547657 | chr2:179412386;179412385;179412384 |
| N2AB | 29682 | 89269;89270;89271 | chr2:178547659;178547658;178547657 | chr2:179412386;179412385;179412384 |
| N2A | 28755 | 86488;86489;86490 | chr2:178547659;178547658;178547657 | chr2:179412386;179412385;179412384 |
| N2B | 22258 | 66997;66998;66999 | chr2:178547659;178547658;178547657 | chr2:179412386;179412385;179412384 |
| Novex-1 | 22383 | 67372;67373;67374 | chr2:178547659;178547658;178547657 | chr2:179412386;179412385;179412384 |
| Novex-2 | 22450 | 67573;67574;67575 | chr2:178547659;178547658;178547657 | chr2:179412386;179412385;179412384 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | None | None | 0.094 | N | 0.595 | 0.314 | 0.315314060047 | gnomAD-4.0.0 | 6.84173E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99437E-07 | 0 | 0 |
| A/P | rs1183094083  |
-0.789 | 0.638 | N | 0.621 | 0.242 | 0.326074293725 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| A/P | rs1183094083 |
-0.789 | 0.638 | N | 0.621 | 0.242 | 0.326074293725 | gnomAD-4.0.0 | 1.59107E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88232E-05 | 0 | 0 | 0 | 0 |
| A/V | rs200345129 |
-0.679 | 0.334 | N | 0.626 | 0.382 | None | gnomAD-2.1.1 | 4.82E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.77E-05 | 1.65563E-04 |
| A/V | rs200345129 |
-0.679 | 0.334 | N | 0.626 | 0.382 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.17623E-04 | 0 | 0 |
| A/V | rs200345129 |
-0.679 | 0.334 | N | 0.626 | 0.382 | None | gnomAD-4.0.0 | 8.3035E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.22856E-05 | None | 0 | 0 | 1.05101E-04 | 0 | 1.44088E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5256 | ambiguous | 0.4742 | ambiguous | -1.198 | Destabilizing | 0.947 | D | 0.634 | neutral | None | None | None | None | N |
| A/D | 0.782 | likely_pathogenic | 0.7051 | pathogenic | -1.702 | Destabilizing | 0.468 | N | 0.646 | neutral | N | 0.471823792 | None | None | N |
| A/E | 0.652 | likely_pathogenic | 0.5657 | pathogenic | -1.706 | Destabilizing | 0.25 | N | 0.645 | neutral | None | None | None | None | N |
| A/F | 0.6747 | likely_pathogenic | 0.6521 | pathogenic | -1.192 | Destabilizing | 0.826 | D | 0.669 | neutral | None | None | None | None | N |
| A/G | 0.2508 | likely_benign | 0.218 | benign | -1.352 | Destabilizing | 0.094 | N | 0.595 | neutral | N | 0.440924882 | None | None | N |
| A/H | 0.8129 | likely_pathogenic | 0.7433 | pathogenic | -1.497 | Destabilizing | 0.947 | D | 0.658 | neutral | None | None | None | None | N |
| A/I | 0.517 | ambiguous | 0.5201 | ambiguous | -0.453 | Destabilizing | 0.7 | D | 0.624 | neutral | None | None | None | None | N |
| A/K | 0.885 | likely_pathogenic | 0.8227 | pathogenic | -1.202 | Destabilizing | 0.25 | N | 0.641 | neutral | None | None | None | None | N |
| A/L | 0.459 | ambiguous | 0.4214 | ambiguous | -0.453 | Destabilizing | 0.399 | N | 0.647 | neutral | None | None | None | None | N |
| A/M | 0.4373 | ambiguous | 0.4379 | ambiguous | -0.421 | Destabilizing | 0.982 | D | 0.627 | neutral | None | None | None | None | N |
| A/N | 0.5867 | likely_pathogenic | 0.5054 | ambiguous | -1.05 | Destabilizing | 0.539 | D | 0.639 | neutral | None | None | None | None | N |
| A/P | 0.49 | ambiguous | 0.4334 | ambiguous | -0.62 | Destabilizing | 0.638 | D | 0.621 | neutral | N | 0.44696542 | None | None | N |
| A/Q | 0.6968 | likely_pathogenic | 0.6101 | pathogenic | -1.217 | Destabilizing | 0.7 | D | 0.647 | neutral | None | None | None | None | N |
| A/R | 0.8338 | likely_pathogenic | 0.7709 | pathogenic | -0.893 | Destabilizing | 0.7 | D | 0.636 | neutral | None | None | None | None | N |
| A/S | 0.0944 | likely_benign | 0.0865 | benign | -1.414 | Destabilizing | 0.001 | N | 0.311 | neutral | N | 0.423797772 | None | None | N |
| A/T | 0.1965 | likely_benign | 0.1768 | benign | -1.325 | Destabilizing | 0.201 | N | 0.582 | neutral | N | 0.467165276 | None | None | N |
| A/V | 0.2566 | likely_benign | 0.2582 | benign | -0.62 | Destabilizing | 0.334 | N | 0.626 | neutral | N | 0.478512036 | None | None | N |
| A/W | 0.9168 | likely_pathogenic | 0.8925 | pathogenic | -1.554 | Destabilizing | 0.982 | D | 0.681 | prob.neutral | None | None | None | None | N |
| A/Y | 0.7718 | likely_pathogenic | 0.7167 | pathogenic | -1.14 | Destabilizing | 0.826 | D | 0.663 | neutral | 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.