Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23781 | 71566;71567;71568 | chr2:178574791;178574790;178574789 | chr2:179439518;179439517;179439516 |
| N2AB | 22140 | 66643;66644;66645 | chr2:178574791;178574790;178574789 | chr2:179439518;179439517;179439516 |
| N2A | 21213 | 63862;63863;63864 | chr2:178574791;178574790;178574789 | chr2:179439518;179439517;179439516 |
| N2B | 14716 | 44371;44372;44373 | chr2:178574791;178574790;178574789 | chr2:179439518;179439517;179439516 |
| Novex-1 | 14841 | 44746;44747;44748 | chr2:178574791;178574790;178574789 | chr2:179439518;179439517;179439516 |
| Novex-2 | 14908 | 44947;44948;44949 | chr2:178574791;178574790;178574789 | chr2:179439518;179439517;179439516 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs146483596  |
-0.125 | 0.999 | N | 0.579 | 0.28 | None | gnomAD-2.1.1 | 4.32E-05 | None | None | None | None | N | None | 2.48242E-04 | 2.84E-05 | None | 0 | 0 | None | 1.64853E-04 | None | 0 | 0 | 0 |
| V/I | rs146483596 |
-0.125 | 0.999 | N | 0.579 | 0.28 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 1.44802E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs146483596 |
-0.125 | 0.999 | N | 0.579 | 0.28 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/I | rs146483596 |
-0.125 | 0.999 | N | 0.579 | 0.28 | None | gnomAD-4.0.0 | 3.53615E-05 | None | None | None | None | N | None | 1.60013E-04 | 1.66889E-05 | None | 0 | 0 | None | 0 | 0 | 2.62991E-05 | 1.32109E-04 | 1.60328E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.662 | likely_pathogenic | 0.6718 | pathogenic | -1.527 | Destabilizing | 0.999 | D | 0.611 | neutral | N | 0.517169293 | None | None | N |
| V/C | 0.9189 | likely_pathogenic | 0.9299 | pathogenic | -1.0 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| V/D | 0.9899 | likely_pathogenic | 0.992 | pathogenic | -1.858 | Destabilizing | 1.0 | D | 0.865 | deleterious | N | 0.470822126 | None | None | N |
| V/E | 0.9695 | likely_pathogenic | 0.9712 | pathogenic | -1.6 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| V/F | 0.8648 | likely_pathogenic | 0.8504 | pathogenic | -0.814 | Destabilizing | 1.0 | D | 0.815 | deleterious | N | 0.487978556 | None | None | N |
| V/G | 0.8828 | likely_pathogenic | 0.8972 | pathogenic | -2.099 | Highly Destabilizing | 1.0 | D | 0.82 | deleterious | N | 0.461272565 | None | None | N |
| V/H | 0.9903 | likely_pathogenic | 0.9919 | pathogenic | -2.039 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| V/I | 0.0983 | likely_benign | 0.107 | benign | 0.075 | Stabilizing | 0.999 | D | 0.579 | neutral | N | 0.449312292 | None | None | N |
| V/K | 0.9814 | likely_pathogenic | 0.9824 | pathogenic | -1.029 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| V/L | 0.6407 | likely_pathogenic | 0.6209 | pathogenic | 0.075 | Stabilizing | 0.999 | D | 0.607 | neutral | N | 0.511302113 | None | None | N |
| V/M | 0.5414 | ambiguous | 0.5185 | ambiguous | -0.086 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| V/N | 0.9186 | likely_pathogenic | 0.935 | pathogenic | -1.424 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| V/P | 0.9731 | likely_pathogenic | 0.9839 | pathogenic | -0.431 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| V/Q | 0.957 | likely_pathogenic | 0.9606 | pathogenic | -1.155 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| V/R | 0.9745 | likely_pathogenic | 0.9739 | pathogenic | -1.17 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| V/S | 0.8181 | likely_pathogenic | 0.8507 | pathogenic | -2.07 | Highly Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| V/T | 0.7041 | likely_pathogenic | 0.7171 | pathogenic | -1.649 | Destabilizing | 0.999 | D | 0.625 | neutral | None | None | None | None | N |
| V/W | 0.9979 | likely_pathogenic | 0.9978 | pathogenic | -1.368 | Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| V/Y | 0.9864 | likely_pathogenic | 0.9861 | pathogenic | -0.886 | Destabilizing | 1.0 | D | 0.825 | 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.