Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21000 | 63223;63224;63225 | chr2:178588727;178588726;178588725 | chr2:179453454;179453453;179453452 |
| N2AB | 19359 | 58300;58301;58302 | chr2:178588727;178588726;178588725 | chr2:179453454;179453453;179453452 |
| N2A | 18432 | 55519;55520;55521 | chr2:178588727;178588726;178588725 | chr2:179453454;179453453;179453452 |
| N2B | 11935 | 36028;36029;36030 | chr2:178588727;178588726;178588725 | chr2:179453454;179453453;179453452 |
| Novex-1 | 12060 | 36403;36404;36405 | chr2:178588727;178588726;178588725 | chr2:179453454;179453453;179453452 |
| Novex-2 | 12127 | 36604;36605;36606 | chr2:178588727;178588726;178588725 | chr2:179453454;179453453;179453452 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs772733348  |
-1.918 | 1.0 | D | 0.729 | 0.412 | 0.459552425292 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65893E-04 |
| L/F | rs772733348 |
-1.918 | 1.0 | D | 0.729 | 0.412 | 0.459552425292 | gnomAD-4.0.0 | 2.73782E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.47464E-04 | 8.99679E-07 | 0 | 1.657E-05 |
| L/M | None | None | 1.0 | N | 0.679 | 0.344 | 0.410071178582 | gnomAD-4.0.0 | 1.59246E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86013E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9324 | likely_pathogenic | 0.9193 | pathogenic | -3.156 | Highly Destabilizing | 0.999 | D | 0.624 | neutral | None | None | None | None | N |
| L/C | 0.9107 | likely_pathogenic | 0.8902 | pathogenic | -2.336 | Highly Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| L/D | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -3.966 | Highly Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| L/E | 0.998 | likely_pathogenic | 0.9974 | pathogenic | -3.652 | Highly Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| L/F | 0.9184 | likely_pathogenic | 0.9131 | pathogenic | -1.901 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | D | 0.523295828 | None | None | N |
| L/G | 0.9959 | likely_pathogenic | 0.9945 | pathogenic | -3.74 | Highly Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| L/H | 0.9967 | likely_pathogenic | 0.9954 | pathogenic | -3.32 | Highly Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| L/I | 0.115 | likely_benign | 0.114 | benign | -1.383 | Destabilizing | 0.999 | D | 0.534 | neutral | None | None | None | None | N |
| L/K | 0.9968 | likely_pathogenic | 0.9956 | pathogenic | -2.664 | Highly Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| L/M | 0.5088 | ambiguous | 0.4752 | ambiguous | -1.49 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.483542146 | None | None | N |
| L/N | 0.9988 | likely_pathogenic | 0.9984 | pathogenic | -3.382 | Highly Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| L/P | 0.995 | likely_pathogenic | 0.9934 | pathogenic | -1.968 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| L/Q | 0.9928 | likely_pathogenic | 0.9897 | pathogenic | -3.058 | Highly Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| L/R | 0.9918 | likely_pathogenic | 0.9894 | pathogenic | -2.547 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| L/S | 0.9949 | likely_pathogenic | 0.9929 | pathogenic | -3.899 | Highly Destabilizing | 1.0 | D | 0.789 | deleterious | D | 0.523549318 | None | None | N |
| L/T | 0.9334 | likely_pathogenic | 0.9145 | pathogenic | -3.435 | Highly Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| L/V | 0.1096 | likely_benign | 0.1088 | benign | -1.968 | Destabilizing | 0.999 | D | 0.591 | neutral | N | 0.408417314 | None | None | N |
| L/W | 0.9935 | likely_pathogenic | 0.9917 | pathogenic | -2.325 | Highly Destabilizing | 1.0 | D | 0.673 | neutral | D | 0.523549318 | None | None | N |
| L/Y | 0.9954 | likely_pathogenic | 0.9939 | pathogenic | -2.175 | Highly Destabilizing | 1.0 | D | 0.719 | prob.delet. | 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.