Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26843 | 80752;80753;80754 | chr2:178565605;178565604;178565603 | chr2:179430332;179430331;179430330 |
| N2AB | 25202 | 75829;75830;75831 | chr2:178565605;178565604;178565603 | chr2:179430332;179430331;179430330 |
| N2A | 24275 | 73048;73049;73050 | chr2:178565605;178565604;178565603 | chr2:179430332;179430331;179430330 |
| N2B | 17778 | 53557;53558;53559 | chr2:178565605;178565604;178565603 | chr2:179430332;179430331;179430330 |
| Novex-1 | 17903 | 53932;53933;53934 | chr2:178565605;178565604;178565603 | chr2:179430332;179430331;179430330 |
| Novex-2 | 17970 | 54133;54134;54135 | chr2:178565605;178565604;178565603 | chr2:179430332;179430331;179430330 |
| 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 | None | None | 1.0 | D | 0.871 | 0.667 | 0.790107933513 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| L/M | rs142004835  |
-1.473 | 0.999 | D | 0.844 | 0.649 | 0.770200815773 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| L/M | rs142004835 |
-1.473 | 0.999 | D | 0.844 | 0.649 | 0.770200815773 | gnomAD-4.0.0 | 2.73709E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69868E-06 | 0 | 1.657E-05 |
| L/S | rs2154164932 |
None | 1.0 | D | 0.834 | 0.87 | 0.861748897801 | gnomAD-4.0.0 | 1.5916E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.773E-05 | None | 0 | 0 | 0 | 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 | 0.967 | likely_pathogenic | 0.9654 | pathogenic | -2.414 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| L/C | 0.9152 | likely_pathogenic | 0.9139 | pathogenic | -2.448 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| L/D | 0.9991 | likely_pathogenic | 0.9992 | pathogenic | -2.139 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/E | 0.9957 | likely_pathogenic | 0.9959 | pathogenic | -2.046 | Highly Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| L/F | 0.7454 | likely_pathogenic | 0.7602 | pathogenic | -1.944 | Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.628062062 | None | None | N |
| L/G | 0.9893 | likely_pathogenic | 0.9895 | pathogenic | -2.812 | Highly Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| L/H | 0.9866 | likely_pathogenic | 0.9882 | pathogenic | -1.985 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| L/I | 0.4245 | ambiguous | 0.4384 | ambiguous | -1.324 | Destabilizing | 0.993 | D | 0.835 | deleterious | None | None | None | None | N |
| L/K | 0.988 | likely_pathogenic | 0.9902 | pathogenic | -1.76 | Destabilizing | 0.998 | D | 0.834 | deleterious | None | None | None | None | N |
| L/M | 0.4652 | ambiguous | 0.4899 | ambiguous | -1.398 | Destabilizing | 0.999 | D | 0.844 | deleterious | D | 0.632241026 | None | None | N |
| L/N | 0.9919 | likely_pathogenic | 0.9924 | pathogenic | -1.867 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| L/P | 0.9939 | likely_pathogenic | 0.9946 | pathogenic | -1.663 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| L/Q | 0.9789 | likely_pathogenic | 0.9826 | pathogenic | -1.983 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| L/R | 0.9755 | likely_pathogenic | 0.9789 | pathogenic | -1.21 | Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| L/S | 0.9938 | likely_pathogenic | 0.9937 | pathogenic | -2.657 | Highly Destabilizing | 1.0 | D | 0.834 | deleterious | D | 0.670426752 | None | None | N |
| L/T | 0.9751 | likely_pathogenic | 0.9751 | pathogenic | -2.424 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| L/V | 0.5571 | ambiguous | 0.5478 | ambiguous | -1.663 | Destabilizing | 0.993 | D | 0.847 | deleterious | D | 0.6000005 | None | None | N |
| L/W | 0.9671 | likely_pathogenic | 0.9723 | pathogenic | -2.0 | Highly Destabilizing | 1.0 | D | 0.756 | deleterious | D | 0.670426752 | None | None | N |
| L/Y | 0.9764 | likely_pathogenic | 0.9781 | pathogenic | -1.762 | Destabilizing | 0.999 | D | 0.827 | 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.