Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17650 | 53173;53174;53175 | chr2:178607839;178607838;178607837 | chr2:179472566;179472565;179472564 |
| N2AB | 16009 | 48250;48251;48252 | chr2:178607839;178607838;178607837 | chr2:179472566;179472565;179472564 |
| N2A | 15082 | 45469;45470;45471 | chr2:178607839;178607838;178607837 | chr2:179472566;179472565;179472564 |
| N2B | 8585 | 25978;25979;25980 | chr2:178607839;178607838;178607837 | chr2:179472566;179472565;179472564 |
| Novex-1 | 8710 | 26353;26354;26355 | chr2:178607839;178607838;178607837 | chr2:179472566;179472565;179472564 |
| Novex-2 | 8777 | 26554;26555;26556 | chr2:178607839;178607838;178607837 | chr2:179472566;179472565;179472564 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | None | None | 1.0 | N | 0.616 | 0.339 | 0.259761712551 | gnomAD-4.0.0 | 6.84498E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99758E-07 | 0 | 0 |
| A/T | rs535008556  |
-0.469 | 1.0 | N | 0.765 | 0.404 | 0.300110245524 | gnomAD-2.1.1 | 1.48987E-04 | None | None | None | None | I | None | 0 | 5.8E-05 | None | 0 | 0 | None | 1.11118E-03 | None | 0 | 8.9E-06 | 0 |
| A/T | rs535008556 |
-0.469 | 1.0 | N | 0.765 | 0.404 | 0.300110245524 | gnomAD-3.1.2 | 6.58E-05 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 1.86335E-03 | 0 |
| A/T | rs535008556 |
-0.469 | 1.0 | N | 0.765 | 0.404 | 0.300110245524 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| A/T | rs535008556 |
-0.469 | 1.0 | N | 0.765 | 0.404 | 0.300110245524 | gnomAD-4.0.0 | 9.29935E-05 | None | None | None | None | I | None | 0 | 8.3375E-05 | None | 0 | 0 | None | 0 | 0 | 3.64613E-05 | 1.06518E-03 | 8.00897E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.536 | ambiguous | 0.5425 | ambiguous | -0.789 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
| A/D | 0.8156 | likely_pathogenic | 0.7455 | pathogenic | -0.584 | Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | I |
| A/E | 0.6577 | likely_pathogenic | 0.5776 | pathogenic | -0.749 | Destabilizing | 1.0 | D | 0.788 | deleterious | N | 0.475888235 | None | None | I |
| A/F | 0.5824 | likely_pathogenic | 0.5138 | ambiguous | -1.002 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
| A/G | 0.2431 | likely_benign | 0.2107 | benign | -0.347 | Destabilizing | 1.0 | D | 0.612 | neutral | N | 0.490870913 | None | None | I |
| A/H | 0.807 | likely_pathogenic | 0.7589 | pathogenic | -0.353 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | I |
| A/I | 0.419 | ambiguous | 0.3695 | ambiguous | -0.456 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| A/K | 0.7999 | likely_pathogenic | 0.7425 | pathogenic | -0.628 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | I |
| A/L | 0.4362 | ambiguous | 0.3845 | ambiguous | -0.456 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| A/M | 0.4338 | ambiguous | 0.3926 | ambiguous | -0.424 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | I |
| A/N | 0.6877 | likely_pathogenic | 0.6122 | pathogenic | -0.326 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | I |
| A/P | 0.9172 | likely_pathogenic | 0.9081 | pathogenic | -0.381 | Destabilizing | 1.0 | D | 0.805 | deleterious | N | 0.51291012 | None | None | I |
| A/Q | 0.6561 | likely_pathogenic | 0.6017 | pathogenic | -0.636 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | I |
| A/R | 0.6831 | likely_pathogenic | 0.642 | pathogenic | -0.125 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | I |
| A/S | 0.1718 | likely_benign | 0.1621 | benign | -0.503 | Destabilizing | 1.0 | D | 0.616 | neutral | N | 0.516769435 | None | None | I |
| A/T | 0.2462 | likely_benign | 0.2093 | benign | -0.594 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.482271018 | None | None | I |
| A/V | 0.1842 | likely_benign | 0.1675 | benign | -0.381 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.449293649 | None | None | I |
| A/W | 0.9256 | likely_pathogenic | 0.9124 | pathogenic | -1.107 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | I |
| A/Y | 0.7924 | likely_pathogenic | 0.7464 | pathogenic | -0.776 | Destabilizing | 1.0 | D | 0.86 | 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.