Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30155 | 90688;90689;90690 | chr2:178552437;178552436;178552435 | chr2:179417164;179417163;179417162 |
| N2AB | 28514 | 85765;85766;85767 | chr2:178552437;178552436;178552435 | chr2:179417164;179417163;179417162 |
| N2A | 27587 | 82984;82985;82986 | chr2:178552437;178552436;178552435 | chr2:179417164;179417163;179417162 |
| N2B | 21090 | 63493;63494;63495 | chr2:178552437;178552436;178552435 | chr2:179417164;179417163;179417162 |
| Novex-1 | 21215 | 63868;63869;63870 | chr2:178552437;178552436;178552435 | chr2:179417164;179417163;179417162 |
| Novex-2 | 21282 | 64069;64070;64071 | chr2:178552437;178552436;178552435 | chr2:179417164;179417163;179417162 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs918516226  |
-1.486 | 1.0 | D | 0.754 | 0.374 | 0.442977140156 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/C | rs918516226 |
-1.486 | 1.0 | D | 0.754 | 0.374 | 0.442977140156 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Y/C | rs918516226 |
-1.486 | 1.0 | D | 0.754 | 0.374 | 0.442977140156 | gnomAD-4.0.0 | 1.87219E-06 | None | None | None | None | N | None | 1.33829E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.53477E-07 | 0 | 1.61457E-05 |
| Y/H | None | None | 0.999 | N | 0.707 | 0.533 | 0.402326594622 | gnomAD-4.0.0 | 2.40066E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31251E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.8826 | likely_pathogenic | 0.8498 | pathogenic | -2.576 | Highly Destabilizing | 0.996 | D | 0.741 | deleterious | None | None | None | None | N |
| Y/C | 0.2016 | likely_benign | 0.1802 | benign | -1.525 | Destabilizing | 1.0 | D | 0.754 | deleterious | D | 0.529883166 | None | None | N |
| Y/D | 0.988 | likely_pathogenic | 0.9802 | pathogenic | -2.142 | Highly Destabilizing | 0.999 | D | 0.799 | deleterious | N | 0.496226168 | None | None | N |
| Y/E | 0.9904 | likely_pathogenic | 0.9841 | pathogenic | -1.978 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| Y/F | 0.0836 | likely_benign | 0.0751 | benign | -0.853 | Destabilizing | 0.217 | N | 0.221 | neutral | N | 0.441917465 | None | None | N |
| Y/G | 0.9221 | likely_pathogenic | 0.8867 | pathogenic | -2.972 | Highly Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| Y/H | 0.7364 | likely_pathogenic | 0.6606 | pathogenic | -1.49 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | N | 0.496226168 | None | None | N |
| Y/I | 0.5385 | ambiguous | 0.4563 | ambiguous | -1.313 | Destabilizing | 0.998 | D | 0.775 | deleterious | None | None | None | None | N |
| Y/K | 0.9835 | likely_pathogenic | 0.9727 | pathogenic | -1.85 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | N |
| Y/L | 0.6312 | likely_pathogenic | 0.5861 | pathogenic | -1.313 | Destabilizing | 0.983 | D | 0.669 | neutral | None | None | None | None | N |
| Y/M | 0.8045 | likely_pathogenic | 0.745 | pathogenic | -1.084 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| Y/N | 0.9236 | likely_pathogenic | 0.872 | pathogenic | -2.46 | Highly Destabilizing | 0.999 | D | 0.775 | deleterious | N | 0.496226168 | None | None | N |
| Y/P | 0.9894 | likely_pathogenic | 0.9866 | pathogenic | -1.739 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| Y/Q | 0.9611 | likely_pathogenic | 0.9385 | pathogenic | -2.24 | Highly Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| Y/R | 0.948 | likely_pathogenic | 0.9249 | pathogenic | -1.574 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| Y/S | 0.8218 | likely_pathogenic | 0.7552 | pathogenic | -2.91 | Highly Destabilizing | 0.999 | D | 0.783 | deleterious | N | 0.499906976 | None | None | N |
| Y/T | 0.9073 | likely_pathogenic | 0.8624 | pathogenic | -2.632 | Highly Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| Y/V | 0.4167 | ambiguous | 0.3654 | ambiguous | -1.739 | Destabilizing | 0.992 | D | 0.74 | deleterious | None | None | None | None | N |
| Y/W | 0.4656 | ambiguous | 0.4437 | ambiguous | -0.315 | Destabilizing | 1.0 | D | 0.704 | prob.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.