Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30356 | 91291;91292;91293 | chr2:178551834;178551833;178551832 | chr2:179416561;179416560;179416559 |
| N2AB | 28715 | 86368;86369;86370 | chr2:178551834;178551833;178551832 | chr2:179416561;179416560;179416559 |
| N2A | 27788 | 83587;83588;83589 | chr2:178551834;178551833;178551832 | chr2:179416561;179416560;179416559 |
| N2B | 21291 | 64096;64097;64098 | chr2:178551834;178551833;178551832 | chr2:179416561;179416560;179416559 |
| Novex-1 | 21416 | 64471;64472;64473 | chr2:178551834;178551833;178551832 | chr2:179416561;179416560;179416559 |
| Novex-2 | 21483 | 64672;64673;64674 | chr2:178551834;178551833;178551832 | chr2:179416561;179416560;179416559 |
| 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 | rs780689608  |
-1.319 | 0.78 | N | 0.655 | 0.408 | 0.555237559564 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs780689608 |
-1.319 | 0.78 | N | 0.655 | 0.408 | 0.555237559564 | gnomAD-4.0.0 | 1.59111E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77285E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs752225531 |
-0.627 | 0.011 | N | 0.225 | 0.079 | 0.237489013734 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs752225531 |
-0.627 | 0.011 | N | 0.225 | 0.079 | 0.237489013734 | gnomAD-4.0.0 | 1.59111E-06 | None | None | None | None | I | None | 0 | 2.28634E-05 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7988 | likely_pathogenic | 0.8001 | pathogenic | -1.774 | Destabilizing | 0.78 | D | 0.655 | neutral | N | 0.485348891 | None | None | I |
| V/C | 0.9412 | likely_pathogenic | 0.9316 | pathogenic | -1.298 | Destabilizing | 0.999 | D | 0.747 | deleterious | None | None | None | None | I |
| V/D | 0.9783 | likely_pathogenic | 0.9758 | pathogenic | -1.73 | Destabilizing | 0.995 | D | 0.864 | deleterious | N | 0.487550936 | None | None | I |
| V/E | 0.9473 | likely_pathogenic | 0.9398 | pathogenic | -1.709 | Destabilizing | 0.996 | D | 0.848 | deleterious | None | None | None | None | I |
| V/F | 0.6912 | likely_pathogenic | 0.6969 | pathogenic | -1.452 | Destabilizing | 0.968 | D | 0.794 | deleterious | N | 0.49467728 | None | None | I |
| V/G | 0.8763 | likely_pathogenic | 0.868 | pathogenic | -2.125 | Highly Destabilizing | 0.995 | D | 0.856 | deleterious | N | 0.515823409 | None | None | I |
| V/H | 0.985 | likely_pathogenic | 0.9837 | pathogenic | -1.626 | Destabilizing | 0.999 | D | 0.835 | deleterious | None | None | None | None | I |
| V/I | 0.064 | likely_benign | 0.064 | benign | -0.894 | Destabilizing | 0.011 | N | 0.225 | neutral | N | 0.380409567 | None | None | I |
| V/K | 0.9604 | likely_pathogenic | 0.9544 | pathogenic | -1.38 | Destabilizing | 0.988 | D | 0.85 | deleterious | None | None | None | None | I |
| V/L | 0.3701 | ambiguous | 0.3547 | ambiguous | -0.894 | Destabilizing | 0.437 | N | 0.442 | neutral | N | 0.49579673 | None | None | I |
| V/M | 0.3972 | ambiguous | 0.3933 | ambiguous | -0.664 | Destabilizing | 0.976 | D | 0.681 | prob.neutral | None | None | None | None | I |
| V/N | 0.9121 | likely_pathogenic | 0.908 | pathogenic | -1.239 | Destabilizing | 0.996 | D | 0.863 | deleterious | None | None | None | None | I |
| V/P | 0.8236 | likely_pathogenic | 0.811 | pathogenic | -1.154 | Destabilizing | 0.996 | D | 0.847 | deleterious | None | None | None | None | I |
| V/Q | 0.9568 | likely_pathogenic | 0.9516 | pathogenic | -1.412 | Destabilizing | 0.996 | D | 0.839 | deleterious | None | None | None | None | I |
| V/R | 0.9575 | likely_pathogenic | 0.9498 | pathogenic | -0.843 | Destabilizing | 0.996 | D | 0.865 | deleterious | None | None | None | None | I |
| V/S | 0.9124 | likely_pathogenic | 0.9078 | pathogenic | -1.812 | Destabilizing | 0.988 | D | 0.827 | deleterious | None | None | None | None | I |
| V/T | 0.7798 | likely_pathogenic | 0.7687 | pathogenic | -1.674 | Destabilizing | 0.919 | D | 0.739 | prob.delet. | None | None | None | None | I |
| V/W | 0.9875 | likely_pathogenic | 0.9866 | pathogenic | -1.65 | Destabilizing | 0.999 | D | 0.795 | deleterious | None | None | None | None | I |
| V/Y | 0.9472 | likely_pathogenic | 0.9427 | pathogenic | -1.358 | Destabilizing | 0.996 | D | 0.774 | deleterious | None | None | None | None | I |
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.