Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31695 | 95308;95309;95310 | chr2:178546248;178546247;178546246 | chr2:179410975;179410974;179410973 |
| N2AB | 30054 | 90385;90386;90387 | chr2:178546248;178546247;178546246 | chr2:179410975;179410974;179410973 |
| N2A | 29127 | 87604;87605;87606 | chr2:178546248;178546247;178546246 | chr2:179410975;179410974;179410973 |
| N2B | 22630 | 68113;68114;68115 | chr2:178546248;178546247;178546246 | chr2:179410975;179410974;179410973 |
| Novex-1 | 22755 | 68488;68489;68490 | chr2:178546248;178546247;178546246 | chr2:179410975;179410974;179410973 |
| Novex-2 | 22822 | 68689;68690;68691 | chr2:178546248;178546247;178546246 | chr2:179410975;179410974;179410973 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/R | rs376403373  |
0.042 | 1.0 | D | 0.909 | 0.824 | 0.79156988546 | gnomAD-2.1.1 | 5.36E-05 | None | None | None | None | I | None | 1.6533E-04 | 0 | None | 0 | 1.02428E-04 | None | 3.28E-05 | None | 0 | 4.7E-05 | 2.81136E-04 |
| G/R | rs376403373 |
0.042 | 1.0 | D | 0.909 | 0.824 | 0.79156988546 | gnomAD-3.1.2 | 1.05152E-04 | None | None | None | None | I | None | 2.41394E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| G/R | rs376403373 |
0.042 | 1.0 | D | 0.909 | 0.824 | 0.79156988546 | gnomAD-4.0.0 | 8.55507E-05 | None | None | None | None | I | None | 2.00315E-04 | 1.66722E-05 | None | 0 | 6.683E-05 | None | 0 | 0 | 9.4973E-05 | 2.19722E-05 | 8.00666E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.895 | likely_pathogenic | 0.8512 | pathogenic | -0.226 | Destabilizing | 1.0 | D | 0.767 | deleterious | D | 0.603622308 | None | None | I |
| G/C | 0.9674 | likely_pathogenic | 0.9571 | pathogenic | -0.878 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | I |
| G/D | 0.9772 | likely_pathogenic | 0.9722 | pathogenic | -0.649 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | I |
| G/E | 0.9902 | likely_pathogenic | 0.9867 | pathogenic | -0.819 | Destabilizing | 1.0 | D | 0.877 | deleterious | D | 0.546830674 | None | None | I |
| G/F | 0.9958 | likely_pathogenic | 0.9942 | pathogenic | -1.061 | Destabilizing | 1.0 | D | 0.885 | deleterious | None | None | None | None | I |
| G/H | 0.9941 | likely_pathogenic | 0.9917 | pathogenic | -0.409 | Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | I |
| G/I | 0.9958 | likely_pathogenic | 0.9945 | pathogenic | -0.49 | Destabilizing | 1.0 | D | 0.888 | deleterious | None | None | None | None | I |
| G/K | 0.9943 | likely_pathogenic | 0.9913 | pathogenic | -0.656 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | I |
| G/L | 0.9926 | likely_pathogenic | 0.9895 | pathogenic | -0.49 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | I |
| G/M | 0.9955 | likely_pathogenic | 0.9933 | pathogenic | -0.53 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
| G/N | 0.9811 | likely_pathogenic | 0.9723 | pathogenic | -0.351 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | I |
| G/P | 0.9996 | likely_pathogenic | 0.9995 | pathogenic | -0.375 | Destabilizing | 1.0 | D | 0.906 | deleterious | None | None | None | None | I |
| G/Q | 0.9868 | likely_pathogenic | 0.9797 | pathogenic | -0.647 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | I |
| G/R | 0.9799 | likely_pathogenic | 0.9728 | pathogenic | -0.223 | Destabilizing | 1.0 | D | 0.909 | deleterious | D | 0.636094999 | None | None | I |
| G/S | 0.8284 | likely_pathogenic | 0.7696 | pathogenic | -0.451 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | I |
| G/T | 0.9803 | likely_pathogenic | 0.9708 | pathogenic | -0.561 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | I |
| G/V | 0.9898 | likely_pathogenic | 0.9869 | pathogenic | -0.375 | Destabilizing | 1.0 | D | 0.876 | deleterious | D | 0.636700412 | None | None | I |
| G/W | 0.9933 | likely_pathogenic | 0.9924 | pathogenic | -1.177 | Destabilizing | 1.0 | D | 0.867 | deleterious | D | 0.63710402 | None | None | I |
| G/Y | 0.9941 | likely_pathogenic | 0.9922 | pathogenic | -0.847 | Destabilizing | 1.0 | D | 0.883 | 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.