Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32085 | 96478;96479;96480 | chr2:178543891;178543890;178543889 | chr2:179408618;179408617;179408616 |
| N2AB | 30444 | 91555;91556;91557 | chr2:178543891;178543890;178543889 | chr2:179408618;179408617;179408616 |
| N2A | 29517 | 88774;88775;88776 | chr2:178543891;178543890;178543889 | chr2:179408618;179408617;179408616 |
| N2B | 23020 | 69283;69284;69285 | chr2:178543891;178543890;178543889 | chr2:179408618;179408617;179408616 |
| Novex-1 | 23145 | 69658;69659;69660 | chr2:178543891;178543890;178543889 | chr2:179408618;179408617;179408616 |
| Novex-2 | 23212 | 69859;69860;69861 | chr2:178543891;178543890;178543889 | chr2:179408618;179408617;179408616 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs761147994  |
-0.768 | 0.889 | N | 0.443 | 0.178 | 0.264081493735 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| I/L | rs761147994 |
-0.768 | 0.889 | N | 0.443 | 0.178 | 0.264081493735 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/L | rs761147994 |
-0.768 | 0.889 | N | 0.443 | 0.178 | 0.264081493735 | gnomAD-4.0.0 | 1.05353E-05 | None | None | None | None | N | None | 1.3354E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.35624E-05 | 0 | 0 |
| I/T | None | None | 0.989 | N | 0.739 | 0.412 | 0.561027722634 | gnomAD-4.0.0 | 1.59147E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85878E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6633 | likely_pathogenic | 0.6441 | pathogenic | -2.3 | Highly Destabilizing | 0.992 | D | 0.725 | prob.delet. | None | None | None | None | N |
| I/C | 0.9239 | likely_pathogenic | 0.912 | pathogenic | -2.002 | Highly Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| I/D | 0.9992 | likely_pathogenic | 0.999 | pathogenic | -1.904 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| I/E | 0.9962 | likely_pathogenic | 0.9954 | pathogenic | -1.761 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| I/F | 0.6261 | likely_pathogenic | 0.5881 | pathogenic | -1.569 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | N | 0.470908567 | None | None | N |
| I/G | 0.9837 | likely_pathogenic | 0.9812 | pathogenic | -2.771 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| I/H | 0.997 | likely_pathogenic | 0.9961 | pathogenic | -2.068 | Highly Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| I/K | 0.9937 | likely_pathogenic | 0.9917 | pathogenic | -1.548 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| I/L | 0.1576 | likely_benign | 0.1404 | benign | -0.986 | Destabilizing | 0.889 | D | 0.443 | neutral | N | 0.342037606 | None | None | N |
| I/M | 0.1825 | likely_benign | 0.1689 | benign | -1.068 | Destabilizing | 0.998 | D | 0.67 | neutral | N | 0.482645714 | None | None | N |
| I/N | 0.9926 | likely_pathogenic | 0.9898 | pathogenic | -1.663 | Destabilizing | 0.999 | D | 0.839 | deleterious | N | 0.462239481 | None | None | N |
| I/P | 0.995 | likely_pathogenic | 0.9945 | pathogenic | -1.4 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| I/Q | 0.9928 | likely_pathogenic | 0.9911 | pathogenic | -1.664 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| I/R | 0.9889 | likely_pathogenic | 0.9855 | pathogenic | -1.183 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| I/S | 0.9566 | likely_pathogenic | 0.9464 | pathogenic | -2.481 | Highly Destabilizing | 0.998 | D | 0.791 | deleterious | N | 0.461985991 | None | None | N |
| I/T | 0.7456 | likely_pathogenic | 0.7014 | pathogenic | -2.189 | Highly Destabilizing | 0.989 | D | 0.739 | prob.delet. | N | 0.461732502 | None | None | N |
| I/V | 0.0716 | likely_benign | 0.0714 | benign | -1.4 | Destabilizing | 0.333 | N | 0.321 | neutral | N | 0.363778315 | None | None | N |
| I/W | 0.9913 | likely_pathogenic | 0.9901 | pathogenic | -1.733 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| I/Y | 0.9776 | likely_pathogenic | 0.9716 | pathogenic | -1.472 | Destabilizing | 1.0 | D | 0.744 | 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.