Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1728 | 5407;5408;5409 | chr2:178776682;178776681;178776680 | chr2:179641409;179641408;179641407 |
| N2AB | 1728 | 5407;5408;5409 | chr2:178776682;178776681;178776680 | chr2:179641409;179641408;179641407 |
| N2A | 1728 | 5407;5408;5409 | chr2:178776682;178776681;178776680 | chr2:179641409;179641408;179641407 |
| N2B | 1682 | 5269;5270;5271 | chr2:178776682;178776681;178776680 | chr2:179641409;179641408;179641407 |
| Novex-1 | 1682 | 5269;5270;5271 | chr2:178776682;178776681;178776680 | chr2:179641409;179641408;179641407 |
| Novex-2 | 1682 | 5269;5270;5271 | chr2:178776682;178776681;178776680 | chr2:179641409;179641408;179641407 |
| Novex-3 | 1728 | 5407;5408;5409 | chr2:178776682;178776681;178776680 | chr2:179641409;179641408;179641407 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs371837040  |
-0.189 | 1.0 | D | 0.749 | 0.788 | None | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| P/L | rs371837040 |
-0.189 | 1.0 | D | 0.749 | 0.788 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/L | rs371837040 |
-0.189 | 1.0 | D | 0.749 | 0.788 | None | gnomAD-4.0.0 | 3.84214E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.17532E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.9022 | likely_pathogenic | 0.9077 | pathogenic | -0.836 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | D | 0.626300086 | None | None | I |
| P/C | 0.9963 | likely_pathogenic | 0.9968 | pathogenic | -0.48 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| P/D | 0.9977 | likely_pathogenic | 0.9979 | pathogenic | -0.759 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| P/E | 0.9941 | likely_pathogenic | 0.9943 | pathogenic | -0.846 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| P/F | 0.999 | likely_pathogenic | 0.9993 | pathogenic | -0.893 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| P/G | 0.9815 | likely_pathogenic | 0.9831 | pathogenic | -1.036 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | I |
| P/H | 0.9919 | likely_pathogenic | 0.9942 | pathogenic | -0.671 | Destabilizing | 1.0 | D | 0.753 | deleterious | D | 0.713817511 | None | None | I |
| P/I | 0.9943 | likely_pathogenic | 0.9957 | pathogenic | -0.432 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | I |
| P/K | 0.9965 | likely_pathogenic | 0.9973 | pathogenic | -0.774 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | I |
| P/L | 0.9738 | likely_pathogenic | 0.9809 | pathogenic | -0.432 | Destabilizing | 1.0 | D | 0.749 | deleterious | D | 0.714408105 | None | None | I |
| P/M | 0.9951 | likely_pathogenic | 0.9962 | pathogenic | -0.319 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | I |
| P/N | 0.9937 | likely_pathogenic | 0.9944 | pathogenic | -0.375 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| P/Q | 0.9879 | likely_pathogenic | 0.9907 | pathogenic | -0.626 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| P/R | 0.9884 | likely_pathogenic | 0.9911 | pathogenic | -0.22 | Destabilizing | 1.0 | D | 0.757 | deleterious | D | 0.680253768 | None | None | I |
| P/S | 0.9736 | likely_pathogenic | 0.9764 | pathogenic | -0.728 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | D | 0.646617306 | None | None | I |
| P/T | 0.9706 | likely_pathogenic | 0.9734 | pathogenic | -0.72 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | D | 0.660408793 | None | None | I |
| P/V | 0.9794 | likely_pathogenic | 0.9815 | pathogenic | -0.531 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| P/W | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -1.016 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | I |
| P/Y | 0.9985 | likely_pathogenic | 0.9988 | pathogenic | -0.735 | Destabilizing | 1.0 | D | 0.799 | 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.