Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27695 | 83308;83309;83310 | chr2:178563049;178563048;178563047 | chr2:179427776;179427775;179427774 |
| N2AB | 26054 | 78385;78386;78387 | chr2:178563049;178563048;178563047 | chr2:179427776;179427775;179427774 |
| N2A | 25127 | 75604;75605;75606 | chr2:178563049;178563048;178563047 | chr2:179427776;179427775;179427774 |
| N2B | 18630 | 56113;56114;56115 | chr2:178563049;178563048;178563047 | chr2:179427776;179427775;179427774 |
| Novex-1 | 18755 | 56488;56489;56490 | chr2:178563049;178563048;178563047 | chr2:179427776;179427775;179427774 |
| Novex-2 | 18822 | 56689;56690;56691 | chr2:178563049;178563048;178563047 | chr2:179427776;179427775;179427774 |
| 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/I | None | None | 0.999 | D | 0.585 | 0.452 | 0.468253365638 | 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/S | rs772893209  |
-2.499 | 1.0 | D | 0.859 | 0.833 | 0.888304868143 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| L/S | rs772893209 |
-2.499 | 1.0 | D | 0.859 | 0.833 | 0.888304868143 | gnomAD-4.0.0 | 5.47399E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19625E-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 | 0.9784 | likely_pathogenic | 0.9741 | pathogenic | -2.333 | Highly Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| L/C | 0.9485 | likely_pathogenic | 0.9318 | pathogenic | -1.703 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| L/D | 0.9996 | likely_pathogenic | 0.9995 | pathogenic | -2.915 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| L/E | 0.9985 | likely_pathogenic | 0.9979 | pathogenic | -2.658 | Highly Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| L/F | 0.8 | likely_pathogenic | 0.7742 | pathogenic | -1.549 | Destabilizing | 1.0 | D | 0.76 | deleterious | N | 0.491328324 | None | None | N |
| L/G | 0.9966 | likely_pathogenic | 0.9955 | pathogenic | -2.81 | Highly Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| L/H | 0.9942 | likely_pathogenic | 0.9921 | pathogenic | -2.28 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| L/I | 0.2294 | likely_benign | 0.2198 | benign | -0.92 | Destabilizing | 0.999 | D | 0.585 | neutral | D | 0.54182316 | None | None | N |
| L/K | 0.9962 | likely_pathogenic | 0.9952 | pathogenic | -1.966 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| L/M | 0.3792 | ambiguous | 0.364 | ambiguous | -0.968 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | N |
| L/N | 0.997 | likely_pathogenic | 0.9963 | pathogenic | -2.527 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| L/P | 0.9979 | likely_pathogenic | 0.9973 | pathogenic | -1.381 | Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| L/Q | 0.9938 | likely_pathogenic | 0.9916 | pathogenic | -2.275 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| L/R | 0.9938 | likely_pathogenic | 0.9918 | pathogenic | -1.955 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| L/S | 0.9968 | likely_pathogenic | 0.996 | pathogenic | -3.051 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | D | 0.629614031 | None | None | N |
| L/T | 0.9887 | likely_pathogenic | 0.9861 | pathogenic | -2.646 | Highly Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| L/V | 0.4109 | ambiguous | 0.3731 | ambiguous | -1.381 | Destabilizing | 0.999 | D | 0.596 | neutral | D | 0.580314762 | None | None | N |
| L/W | 0.9877 | likely_pathogenic | 0.9844 | pathogenic | -1.802 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| L/Y | 0.9815 | likely_pathogenic | 0.977 | pathogenic | -1.564 | Destabilizing | 1.0 | D | 0.805 | 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.