Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17336 | 52231;52232;52233 | chr2:178609304;178609303;178609302 | chr2:179474031;179474030;179474029 |
| N2AB | 15695 | 47308;47309;47310 | chr2:178609304;178609303;178609302 | chr2:179474031;179474030;179474029 |
| N2A | 14768 | 44527;44528;44529 | chr2:178609304;178609303;178609302 | chr2:179474031;179474030;179474029 |
| N2B | 8271 | 25036;25037;25038 | chr2:178609304;178609303;178609302 | chr2:179474031;179474030;179474029 |
| Novex-1 | 8396 | 25411;25412;25413 | chr2:178609304;178609303;178609302 | chr2:179474031;179474030;179474029 |
| Novex-2 | 8463 | 25612;25613;25614 | chr2:178609304;178609303;178609302 | chr2:179474031;179474030;179474029 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1315720730  |
-1.922 | 0.052 | N | 0.598 | 0.531 | 0.493156425868 | gnomAD-2.1.1 | 4.16E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.47E-05 | None | 0 | 0 | 0 |
| V/A | rs1315720730 |
-1.922 | 0.052 | N | 0.598 | 0.531 | 0.493156425868 | gnomAD-4.0.0 | 1.6174E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.47033E-05 | 0 |
| V/I | rs567781604 |
-0.844 | 0.001 | N | 0.215 | 0.101 | 0.177238962908 | gnomAD-2.1.1 | 4.78E-05 | None | None | None | None | N | None | 4.16E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.62E-05 | 0 |
| V/I | rs567781604 |
-0.844 | 0.001 | N | 0.215 | 0.101 | 0.177238962908 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 2.07383E-04 | 4.78469E-04 |
| V/I | rs567781604 |
-0.844 | 0.001 | N | 0.215 | 0.101 | 0.177238962908 | gnomAD-4.0.0 | 5.0526E-05 | None | None | None | None | N | None | 2.68861E-05 | 3.39732E-05 | None | 0 | 0 | None | 6.29247E-05 | 0 | 5.70352E-05 | 1.12075E-05 | 8.06894E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.8524 | likely_pathogenic | 0.8321 | pathogenic | -2.428 | Highly Destabilizing | 0.052 | N | 0.598 | neutral | N | 0.509903559 | None | None | N |
| V/C | 0.9148 | likely_pathogenic | 0.9068 | pathogenic | -2.214 | Highly Destabilizing | 0.935 | D | 0.807 | deleterious | None | None | None | None | N |
| V/D | 0.9854 | likely_pathogenic | 0.9859 | pathogenic | -3.267 | Highly Destabilizing | 0.484 | N | 0.873 | deleterious | N | 0.510664027 | None | None | N |
| V/E | 0.9585 | likely_pathogenic | 0.9545 | pathogenic | -3.055 | Highly Destabilizing | 0.555 | D | 0.835 | deleterious | None | None | None | None | N |
| V/F | 0.6175 | likely_pathogenic | 0.6071 | pathogenic | -1.414 | Destabilizing | 0.541 | D | 0.802 | deleterious | N | 0.497786785 | None | None | N |
| V/G | 0.8838 | likely_pathogenic | 0.8761 | pathogenic | -2.943 | Highly Destabilizing | 0.484 | N | 0.843 | deleterious | N | 0.510664027 | None | None | N |
| V/H | 0.9827 | likely_pathogenic | 0.9816 | pathogenic | -2.554 | Highly Destabilizing | 0.935 | D | 0.877 | deleterious | None | None | None | None | N |
| V/I | 0.0685 | likely_benign | 0.0768 | benign | -0.98 | Destabilizing | 0.001 | N | 0.215 | neutral | N | 0.40465186399999997 | None | None | N |
| V/K | 0.9634 | likely_pathogenic | 0.9612 | pathogenic | -2.114 | Highly Destabilizing | 0.38 | N | 0.841 | deleterious | None | None | None | None | N |
| V/L | 0.359 | ambiguous | 0.3787 | ambiguous | -0.98 | Destabilizing | 0.01 | N | 0.383 | neutral | N | 0.493269005 | None | None | N |
| V/M | 0.5517 | ambiguous | 0.5336 | ambiguous | -1.219 | Destabilizing | 0.38 | N | 0.686 | prob.neutral | None | None | None | None | N |
| V/N | 0.9565 | likely_pathogenic | 0.9604 | pathogenic | -2.481 | Highly Destabilizing | 0.555 | D | 0.884 | deleterious | None | None | None | None | N |
| V/P | 0.9783 | likely_pathogenic | 0.9806 | pathogenic | -1.439 | Destabilizing | 0.791 | D | 0.881 | deleterious | None | None | None | None | N |
| V/Q | 0.954 | likely_pathogenic | 0.9487 | pathogenic | -2.348 | Highly Destabilizing | 0.791 | D | 0.886 | deleterious | None | None | None | None | N |
| V/R | 0.942 | likely_pathogenic | 0.9414 | pathogenic | -1.827 | Destabilizing | 0.555 | D | 0.889 | deleterious | None | None | None | None | N |
| V/S | 0.9334 | likely_pathogenic | 0.9306 | pathogenic | -3.061 | Highly Destabilizing | 0.081 | N | 0.811 | deleterious | None | None | None | None | N |
| V/T | 0.9103 | likely_pathogenic | 0.901 | pathogenic | -2.716 | Highly Destabilizing | 0.001 | N | 0.358 | neutral | None | None | None | None | N |
| V/W | 0.9823 | likely_pathogenic | 0.981 | pathogenic | -1.906 | Destabilizing | 0.935 | D | 0.863 | deleterious | None | None | None | None | N |
| V/Y | 0.938 | likely_pathogenic | 0.9318 | pathogenic | -1.61 | Destabilizing | 0.555 | D | 0.804 | 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.