Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33128 | 99607;99608;99609 | chr2:178537825;178537824;178537823 | chr2:179402552;179402551;179402550 |
| N2AB | 31487 | 94684;94685;94686 | chr2:178537825;178537824;178537823 | chr2:179402552;179402551;179402550 |
| N2A | 30560 | 91903;91904;91905 | chr2:178537825;178537824;178537823 | chr2:179402552;179402551;179402550 |
| N2B | 24063 | 72412;72413;72414 | chr2:178537825;178537824;178537823 | chr2:179402552;179402551;179402550 |
| Novex-1 | 24188 | 72787;72788;72789 | chr2:178537825;178537824;178537823 | chr2:179402552;179402551;179402550 |
| Novex-2 | 24255 | 72988;72989;72990 | chr2:178537825;178537824;178537823 | chr2:179402552;179402551;179402550 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/H | rs1457575286  |
None | 1.0 | D | 0.819 | 0.642 | 0.698937693345 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/H | rs1457575286 |
None | 1.0 | D | 0.819 | 0.642 | 0.698937693345 | gnomAD-4.0.0 | 6.5735E-06 | None | None | None | None | I | None | 2.41383E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | None | None | 1.0 | D | 0.783 | 0.634 | 0.802141629741 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.9534 | likely_pathogenic | 0.9596 | pathogenic | -0.777 | Destabilizing | 0.998 | D | 0.74 | deleterious | D | 0.572483027 | None | None | I |
| P/C | 0.9968 | likely_pathogenic | 0.9972 | pathogenic | -0.539 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | I |
| P/D | 0.9917 | likely_pathogenic | 0.991 | pathogenic | -0.71 | Destabilizing | 0.998 | D | 0.761 | deleterious | None | None | None | None | I |
| P/E | 0.9903 | likely_pathogenic | 0.9891 | pathogenic | -0.805 | Destabilizing | 0.999 | D | 0.762 | deleterious | None | None | None | None | I |
| P/F | 0.9979 | likely_pathogenic | 0.9982 | pathogenic | -0.857 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | I |
| P/G | 0.9787 | likely_pathogenic | 0.9792 | pathogenic | -0.958 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | I |
| P/H | 0.99 | likely_pathogenic | 0.9883 | pathogenic | -0.553 | Destabilizing | 1.0 | D | 0.819 | deleterious | D | 0.620136359 | None | None | I |
| P/I | 0.9863 | likely_pathogenic | 0.9885 | pathogenic | -0.43 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | I |
| P/K | 0.9929 | likely_pathogenic | 0.9906 | pathogenic | -0.76 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | I |
| P/L | 0.9663 | likely_pathogenic | 0.9659 | pathogenic | -0.43 | Destabilizing | 1.0 | D | 0.783 | deleterious | D | 0.636387885 | None | None | I |
| P/M | 0.9903 | likely_pathogenic | 0.9918 | pathogenic | -0.363 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | I |
| P/N | 0.9886 | likely_pathogenic | 0.9885 | pathogenic | -0.387 | Destabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | I |
| P/Q | 0.9875 | likely_pathogenic | 0.9853 | pathogenic | -0.645 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| P/R | 0.9859 | likely_pathogenic | 0.9822 | pathogenic | -0.187 | Destabilizing | 1.0 | D | 0.815 | deleterious | D | 0.626465525 | None | None | I |
| P/S | 0.9831 | likely_pathogenic | 0.9833 | pathogenic | -0.733 | Destabilizing | 1.0 | D | 0.766 | deleterious | D | 0.551238447 | None | None | I |
| P/T | 0.9656 | likely_pathogenic | 0.9662 | pathogenic | -0.734 | Destabilizing | 1.0 | D | 0.761 | deleterious | D | 0.61973275 | None | None | I |
| P/V | 0.9704 | likely_pathogenic | 0.9758 | pathogenic | -0.511 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| P/W | 0.999 | likely_pathogenic | 0.999 | pathogenic | -0.962 | Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | I |
| P/Y | 0.9966 | likely_pathogenic | 0.9966 | pathogenic | -0.688 | Destabilizing | 1.0 | D | 0.842 | 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.