Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21930 | 66013;66014;66015 | chr2:178583015;178583014;178583013 | chr2:179447742;179447741;179447740 |
| N2AB | 20289 | 61090;61091;61092 | chr2:178583015;178583014;178583013 | chr2:179447742;179447741;179447740 |
| N2A | 19362 | 58309;58310;58311 | chr2:178583015;178583014;178583013 | chr2:179447742;179447741;179447740 |
| N2B | 12865 | 38818;38819;38820 | chr2:178583015;178583014;178583013 | chr2:179447742;179447741;179447740 |
| Novex-1 | 12990 | 39193;39194;39195 | chr2:178583015;178583014;178583013 | chr2:179447742;179447741;179447740 |
| Novex-2 | 13057 | 39394;39395;39396 | chr2:178583015;178583014;178583013 | chr2:179447742;179447741;179447740 |
| 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/E | rs794727432  |
-0.313 | 0.001 | D | 0.303 | 0.313 | 0.331365685468 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | N | None | 0 | 2.95E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.8E-05 | 0 |
| D/E | rs794727432 |
-0.313 | 0.001 | D | 0.303 | 0.313 | 0.331365685468 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/E | rs794727432 |
-0.313 | 0.001 | D | 0.303 | 0.313 | 0.331365685468 | gnomAD-4.0.0 | 1.80611E-05 | None | None | None | None | N | None | 0 | 3.36134E-05 | None | 0 | 0 | None | 0 | 0 | 2.29762E-05 | 0 | 0 |
| D/N | None | None | 0.549 | D | 0.645 | 0.528 | 0.476205827853 | gnomAD-4.0.0 | 1.37605E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80656E-06 | 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 | 0.5463 | ambiguous | 0.4522 | ambiguous | -0.121 | Destabilizing | 0.379 | N | 0.743 | deleterious | D | 0.579098552 | None | None | N |
| D/C | 0.8071 | likely_pathogenic | 0.7848 | pathogenic | 0.045 | Stabilizing | 0.992 | D | 0.824 | deleterious | None | None | None | None | N |
| D/E | 0.3732 | ambiguous | 0.2752 | benign | -0.641 | Destabilizing | 0.001 | N | 0.303 | neutral | D | 0.541670041 | None | None | N |
| D/F | 0.7571 | likely_pathogenic | 0.7248 | pathogenic | 0.533 | Stabilizing | 0.972 | D | 0.835 | deleterious | None | None | None | None | N |
| D/G | 0.6631 | likely_pathogenic | 0.5979 | pathogenic | -0.547 | Destabilizing | 0.549 | D | 0.713 | prob.delet. | D | 0.600659504 | None | None | N |
| D/H | 0.367 | ambiguous | 0.3782 | ambiguous | 0.251 | Stabilizing | 0.896 | D | 0.746 | deleterious | D | 0.541966342 | None | None | N |
| D/I | 0.7934 | likely_pathogenic | 0.7071 | pathogenic | 1.021 | Stabilizing | 0.92 | D | 0.841 | deleterious | None | None | None | None | N |
| D/K | 0.8674 | likely_pathogenic | 0.8345 | pathogenic | 0.037 | Stabilizing | 0.447 | N | 0.678 | prob.neutral | None | None | None | None | N |
| D/L | 0.7704 | likely_pathogenic | 0.6786 | pathogenic | 1.021 | Stabilizing | 0.85 | D | 0.825 | deleterious | None | None | None | None | N |
| D/M | 0.8284 | likely_pathogenic | 0.7678 | pathogenic | 1.433 | Stabilizing | 0.977 | D | 0.822 | deleterious | None | None | None | None | N |
| D/N | 0.2139 | likely_benign | 0.1905 | benign | -0.749 | Destabilizing | 0.549 | D | 0.645 | neutral | D | 0.552178171 | None | None | N |
| D/P | 0.9885 | likely_pathogenic | 0.9845 | pathogenic | 0.669 | Stabilizing | 0.92 | D | 0.757 | deleterious | None | None | None | None | N |
| D/Q | 0.5715 | likely_pathogenic | 0.5027 | ambiguous | -0.479 | Destabilizing | 0.021 | N | 0.405 | neutral | None | None | None | None | N |
| D/R | 0.9024 | likely_pathogenic | 0.8749 | pathogenic | 0.154 | Stabilizing | 0.739 | D | 0.815 | deleterious | None | None | None | None | N |
| D/S | 0.4052 | ambiguous | 0.3405 | ambiguous | -0.984 | Destabilizing | 0.447 | N | 0.618 | neutral | None | None | None | None | N |
| D/T | 0.7223 | likely_pathogenic | 0.6189 | pathogenic | -0.597 | Destabilizing | 0.617 | D | 0.727 | prob.delet. | None | None | None | None | N |
| D/V | 0.6296 | likely_pathogenic | 0.525 | ambiguous | 0.669 | Stabilizing | 0.81 | D | 0.829 | deleterious | D | 0.617082474 | None | None | N |
| D/W | 0.944 | likely_pathogenic | 0.9432 | pathogenic | 0.711 | Stabilizing | 0.992 | D | 0.826 | deleterious | None | None | None | None | N |
| D/Y | 0.3482 | ambiguous | 0.3354 | benign | 0.819 | Stabilizing | 0.963 | D | 0.833 | deleterious | D | 0.616880669 | 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.