Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23247 | 69964;69965;69966 | chr2:178576393;178576392;178576391 | chr2:179441120;179441119;179441118 |
| N2AB | 21606 | 65041;65042;65043 | chr2:178576393;178576392;178576391 | chr2:179441120;179441119;179441118 |
| N2A | 20679 | 62260;62261;62262 | chr2:178576393;178576392;178576391 | chr2:179441120;179441119;179441118 |
| N2B | 14182 | 42769;42770;42771 | chr2:178576393;178576392;178576391 | chr2:179441120;179441119;179441118 |
| Novex-1 | 14307 | 43144;43145;43146 | chr2:178576393;178576392;178576391 | chr2:179441120;179441119;179441118 |
| Novex-2 | 14374 | 43345;43346;43347 | chr2:178576393;178576392;178576391 | chr2:179441120;179441119;179441118 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs115658240  |
-0.657 | 0.442 | N | 0.77 | 0.372 | None | gnomAD-2.1.1 | 2.99485E-03 | None | None | None | None | N | None | 2.7828E-02 | 1.65989E-03 | None | 0 | 0 | None | 9.08E-05 | None | 0 | 7.09E-05 | 1.36193E-03 |
| P/L | rs115658240 |
-0.657 | 0.442 | N | 0.77 | 0.372 | None | gnomAD-3.1.2 | 7.64665E-03 | None | None | None | None | N | None | 2.67331E-02 | 2.55704E-03 | 0 | 0 | 0 | None | 0 | 0 | 7.36E-05 | 0 | 5.75264E-03 |
| P/L | rs115658240 |
-0.657 | 0.442 | N | 0.77 | 0.372 | None | 1000 genomes | 7.78754E-03 | None | None | None | None | N | None | 2.87E-02 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| P/L | rs115658240 |
-0.657 | 0.442 | N | 0.77 | 0.372 | None | gnomAD-4.0.0 | 1.48008E-03 | None | None | None | None | N | None | 2.77394E-02 | 1.99571E-03 | None | 0 | 2.25205E-05 | None | 0 | 1.02951E-03 | 7.47919E-05 | 1.33882E-04 | 1.83878E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1301 | likely_benign | 0.1336 | benign | -1.715 | Destabilizing | None | N | 0.495 | neutral | N | 0.491866123 | None | None | N |
| P/C | 0.6261 | likely_pathogenic | 0.579 | pathogenic | -1.041 | Destabilizing | 0.909 | D | 0.781 | deleterious | None | None | None | None | N |
| P/D | 0.984 | likely_pathogenic | 0.9759 | pathogenic | -1.797 | Destabilizing | 0.567 | D | 0.745 | deleterious | None | None | None | None | N |
| P/E | 0.9502 | likely_pathogenic | 0.9356 | pathogenic | -1.746 | Destabilizing | 0.272 | N | 0.729 | prob.delet. | None | None | None | None | N |
| P/F | 0.8692 | likely_pathogenic | 0.8361 | pathogenic | -1.27 | Destabilizing | 0.726 | D | 0.809 | deleterious | None | None | None | None | N |
| P/G | 0.7302 | likely_pathogenic | 0.6723 | pathogenic | -2.099 | Highly Destabilizing | 0.157 | N | 0.714 | prob.delet. | None | None | None | None | N |
| P/H | 0.8836 | likely_pathogenic | 0.8612 | pathogenic | -1.79 | Destabilizing | 0.968 | D | 0.729 | prob.delet. | None | None | None | None | N |
| P/I | 0.4029 | ambiguous | 0.3725 | ambiguous | -0.729 | Destabilizing | 0.567 | D | 0.789 | deleterious | None | None | None | None | N |
| P/K | 0.9365 | likely_pathogenic | 0.9214 | pathogenic | -1.486 | Destabilizing | 0.272 | N | 0.735 | prob.delet. | None | None | None | None | N |
| P/L | 0.2832 | likely_benign | 0.2311 | benign | -0.729 | Destabilizing | 0.442 | N | 0.77 | deleterious | N | 0.498305813 | None | None | N |
| P/M | 0.634 | likely_pathogenic | 0.5934 | pathogenic | -0.47 | Destabilizing | 0.909 | D | 0.74 | deleterious | None | None | None | None | N |
| P/N | 0.9467 | likely_pathogenic | 0.9269 | pathogenic | -1.334 | Destabilizing | 0.726 | D | 0.741 | deleterious | None | None | None | None | N |
| P/Q | 0.8526 | likely_pathogenic | 0.8263 | pathogenic | -1.43 | Destabilizing | 0.836 | D | 0.711 | prob.delet. | D | 0.532380274 | None | None | N |
| P/R | 0.8821 | likely_pathogenic | 0.8606 | pathogenic | -1.033 | Destabilizing | 0.715 | D | 0.747 | deleterious | D | 0.532380274 | None | None | N |
| P/S | 0.561 | ambiguous | 0.5159 | ambiguous | -1.857 | Destabilizing | 0.124 | N | 0.708 | prob.delet. | N | 0.520605895 | None | None | N |
| P/T | 0.3745 | ambiguous | 0.3481 | ambiguous | -1.691 | Destabilizing | 0.124 | N | 0.734 | prob.delet. | D | 0.531873295 | None | None | N |
| P/V | 0.2726 | likely_benign | 0.2501 | benign | -1.024 | Destabilizing | 0.157 | N | 0.735 | prob.delet. | None | None | None | None | N |
| P/W | 0.965 | likely_pathogenic | 0.9532 | pathogenic | -1.594 | Destabilizing | 0.968 | D | 0.758 | deleterious | None | None | None | None | N |
| P/Y | 0.9282 | likely_pathogenic | 0.9079 | pathogenic | -1.274 | Destabilizing | 0.726 | D | 0.809 | 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.