Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17444 | 52555;52556;52557 | chr2:178608681;178608680;178608679 | chr2:179473408;179473407;179473406 |
| N2AB | 15803 | 47632;47633;47634 | chr2:178608681;178608680;178608679 | chr2:179473408;179473407;179473406 |
| N2A | 14876 | 44851;44852;44853 | chr2:178608681;178608680;178608679 | chr2:179473408;179473407;179473406 |
| N2B | 8379 | 25360;25361;25362 | chr2:178608681;178608680;178608679 | chr2:179473408;179473407;179473406 |
| Novex-1 | 8504 | 25735;25736;25737 | chr2:178608681;178608680;178608679 | chr2:179473408;179473407;179473406 |
| Novex-2 | 8571 | 25936;25937;25938 | chr2:178608681;178608680;178608679 | chr2:179473408;179473407;179473406 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs778094750  |
-1.68 | 1.0 | D | 0.795 | 0.562 | 0.751386037345 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.69E-05 | 0 |
| R/C | rs778094750 |
-1.68 | 1.0 | D | 0.795 | 0.562 | 0.751386037345 | gnomAD-4.0.0 | 8.21883E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00025E-06 | 1.16093E-05 | 1.65887E-05 |
| R/H | rs376080116 |
-2.525 | 0.999 | D | 0.604 | 0.615 | None | gnomAD-2.1.1 | 2.73399E-04 | None | None | None | None | N | None | 5.80672E-04 | 1.33812E-03 | None | 0 | 5.24E-05 | None | 2.29674E-04 | None | 0 | 5.52E-05 | 0 |
| R/H | rs376080116 |
-2.525 | 0.999 | D | 0.604 | 0.615 | None | gnomAD-3.1.2 | 1.25026E-04 | None | None | None | None | N | None | 3.37919E-04 | 2.62398E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs376080116 |
-2.525 | 0.999 | D | 0.604 | 0.615 | None | gnomAD-4.0.0 | 8.31262E-05 | None | None | None | None | N | None | 3.20736E-04 | 9.02316E-04 | None | 0 | 2.24578E-05 | None | 0 | 0 | 3.05342E-05 | 1.64879E-04 | 6.41313E-05 |
| R/S | None | None | 0.219 | D | 0.509 | 0.448 | 0.405012372841 | gnomAD-4.0.0 | 6.84902E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87582E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9527 | likely_pathogenic | 0.9619 | pathogenic | -1.856 | Destabilizing | 0.693 | D | 0.626 | neutral | None | None | None | None | N |
| R/C | 0.5586 | ambiguous | 0.5675 | pathogenic | -1.775 | Destabilizing | 1.0 | D | 0.795 | deleterious | D | 0.538437569 | None | None | N |
| R/D | 0.9967 | likely_pathogenic | 0.9973 | pathogenic | -1.106 | Destabilizing | 0.975 | D | 0.637 | neutral | None | None | None | None | N |
| R/E | 0.9489 | likely_pathogenic | 0.9509 | pathogenic | -0.88 | Destabilizing | 0.916 | D | 0.599 | neutral | None | None | None | None | N |
| R/F | 0.9795 | likely_pathogenic | 0.9835 | pathogenic | -0.884 | Destabilizing | 0.987 | D | 0.812 | deleterious | None | None | None | None | N |
| R/G | 0.9663 | likely_pathogenic | 0.9719 | pathogenic | -2.2 | Highly Destabilizing | 0.913 | D | 0.628 | neutral | D | 0.538184079 | None | None | N |
| R/H | 0.5432 | ambiguous | 0.5515 | ambiguous | -1.986 | Destabilizing | 0.999 | D | 0.604 | neutral | D | 0.538437569 | None | None | N |
| R/I | 0.9091 | likely_pathogenic | 0.9121 | pathogenic | -0.85 | Destabilizing | 0.987 | D | 0.783 | deleterious | None | None | None | None | N |
| R/K | 0.6068 | likely_pathogenic | 0.5943 | pathogenic | -1.235 | Destabilizing | 0.818 | D | 0.656 | neutral | None | None | None | None | N |
| R/L | 0.8664 | likely_pathogenic | 0.8707 | pathogenic | -0.85 | Destabilizing | 0.954 | D | 0.62 | neutral | D | 0.527081264 | None | None | N |
| R/M | 0.9275 | likely_pathogenic | 0.9344 | pathogenic | -1.408 | Destabilizing | 0.999 | D | 0.672 | neutral | None | None | None | None | N |
| R/N | 0.985 | likely_pathogenic | 0.9877 | pathogenic | -1.41 | Destabilizing | 0.916 | D | 0.563 | neutral | None | None | None | None | N |
| R/P | 0.9993 | likely_pathogenic | 0.9993 | pathogenic | -1.175 | Destabilizing | 0.993 | D | 0.7 | prob.neutral | D | 0.550047364 | None | None | N |
| R/Q | 0.4343 | ambiguous | 0.4276 | ambiguous | -1.144 | Destabilizing | 0.975 | D | 0.563 | neutral | None | None | None | None | N |
| R/S | 0.972 | likely_pathogenic | 0.9748 | pathogenic | -2.168 | Highly Destabilizing | 0.219 | N | 0.509 | neutral | D | 0.52353241 | None | None | N |
| R/T | 0.9544 | likely_pathogenic | 0.9538 | pathogenic | -1.735 | Destabilizing | 0.845 | D | 0.589 | neutral | None | None | None | None | N |
| R/V | 0.9155 | likely_pathogenic | 0.9209 | pathogenic | -1.175 | Destabilizing | 0.975 | D | 0.749 | deleterious | None | None | None | None | N |
| R/W | 0.8218 | likely_pathogenic | 0.8328 | pathogenic | -0.498 | Destabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | None | N |
| R/Y | 0.9413 | likely_pathogenic | 0.9524 | pathogenic | -0.374 | Destabilizing | 0.996 | D | 0.751 | 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.