Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15110 | 45553;45554;45555 | chr2:178621496;178621495;178621494 | chr2:179486223;179486222;179486221 |
| N2AB | 13469 | 40630;40631;40632 | chr2:178621496;178621495;178621494 | chr2:179486223;179486222;179486221 |
| N2A | 12542 | 37849;37850;37851 | chr2:178621496;178621495;178621494 | chr2:179486223;179486222;179486221 |
| N2B | 6045 | 18358;18359;18360 | chr2:178621496;178621495;178621494 | chr2:179486223;179486222;179486221 |
| Novex-1 | 6170 | 18733;18734;18735 | chr2:178621496;178621495;178621494 | chr2:179486223;179486222;179486221 |
| Novex-2 | 6237 | 18934;18935;18936 | chr2:178621496;178621495;178621494 | chr2:179486223;179486222;179486221 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs17354992  |
0.103 | 0.002 | N | 0.186 | 0.21 | None | gnomAD-2.1.1 | 7.95716E-03 | None | None | None | None | N | None | 1.20043E-03 | 2.36091E-03 | None | 1.21289E-02 | 5.19E-05 | None | 7.88871E-03 | None | 3.01489E-02 | 7.42054E-03 | 5.92718E-03 |
| D/N | rs17354992 |
0.103 | 0.002 | N | 0.186 | 0.21 | None | gnomAD-3.1.2 | 6.79528E-03 | None | None | None | None | N | None | 1.25622E-03 | 3.94633E-03 | 7.69231E-03 | 1.0951E-02 | 0 | None | 2.8819E-02 | 0 | 7.81871E-03 | 6.41822E-03 | 3.35249E-03 |
| D/N | rs17354992 |
0.103 | 0.002 | N | 0.186 | 0.21 | None | 1000 genomes | 2.99521E-03 | None | None | None | None | N | None | 0 | 2.9E-03 | None | None | 0 | 7E-03 | None | None | None | 6.1E-03 | None |
| D/N | rs17354992 |
0.103 | 0.002 | N | 0.186 | 0.21 | None | gnomAD-4.0.0 | 7.5279E-03 | None | None | None | None | N | None | 1.12132E-03 | 2.7084E-03 | None | 1.07621E-02 | 4.48129E-05 | None | 2.69468E-02 | 6.61813E-04 | 7.38483E-03 | 8.32802E-03 | 5.9478E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1552 | likely_benign | 0.1378 | benign | 0.021 | Stabilizing | 0.019 | N | 0.276 | neutral | N | 0.414605133 | None | None | N |
| D/C | 0.6551 | likely_pathogenic | 0.6547 | pathogenic | 0.296 | Stabilizing | 0.859 | D | 0.481 | neutral | None | None | None | None | N |
| D/E | 0.1694 | likely_benign | 0.1608 | benign | -0.593 | Destabilizing | 0.081 | N | 0.329 | neutral | N | 0.390535488 | None | None | N |
| D/F | 0.5649 | likely_pathogenic | 0.5232 | ambiguous | -0.389 | Destabilizing | 0.667 | D | 0.552 | neutral | None | None | None | None | N |
| D/G | 0.2076 | likely_benign | 0.1828 | benign | -0.204 | Destabilizing | 0.042 | N | 0.326 | neutral | N | 0.446729108 | None | None | N |
| D/H | 0.3224 | likely_benign | 0.2595 | benign | -0.745 | Destabilizing | 0.655 | D | 0.492 | neutral | N | 0.456146634 | None | None | N |
| D/I | 0.3398 | likely_benign | 0.2953 | benign | 0.559 | Stabilizing | 0.004 | N | 0.375 | neutral | None | None | None | None | N |
| D/K | 0.4333 | ambiguous | 0.3329 | benign | 0.128 | Stabilizing | 0.055 | N | 0.45 | neutral | None | None | None | None | N |
| D/L | 0.4145 | ambiguous | 0.3588 | ambiguous | 0.559 | Stabilizing | 0.055 | N | 0.353 | neutral | None | None | None | None | N |
| D/M | 0.5778 | likely_pathogenic | 0.5612 | ambiguous | 0.92 | Stabilizing | 0.667 | D | 0.488 | neutral | None | None | None | None | N |
| D/N | 0.0952 | likely_benign | 0.0865 | benign | 0.032 | Stabilizing | 0.002 | N | 0.186 | neutral | N | 0.438424133 | None | None | N |
| D/P | 0.808 | likely_pathogenic | 0.7727 | pathogenic | 0.405 | Stabilizing | 0.364 | N | 0.492 | neutral | None | None | None | None | N |
| D/Q | 0.3791 | ambiguous | 0.3278 | benign | 0.051 | Stabilizing | 0.22 | N | 0.475 | neutral | None | None | None | None | N |
| D/R | 0.4532 | ambiguous | 0.345 | ambiguous | 0.017 | Stabilizing | 0.22 | N | 0.516 | neutral | None | None | None | None | N |
| D/S | 0.1047 | likely_benign | 0.0981 | benign | -0.11 | Destabilizing | 0.005 | N | 0.158 | neutral | None | None | None | None | N |
| D/T | 0.1909 | likely_benign | 0.1804 | benign | 0.05 | Stabilizing | 0.001 | N | 0.215 | neutral | None | None | None | None | N |
| D/V | 0.2045 | likely_benign | 0.1744 | benign | 0.405 | Stabilizing | 0.042 | N | 0.36 | neutral | N | 0.40294893 | None | None | N |
| D/W | 0.8858 | likely_pathogenic | 0.8637 | pathogenic | -0.494 | Destabilizing | 0.958 | D | 0.526 | neutral | None | None | None | None | N |
| D/Y | 0.2414 | likely_benign | 0.1968 | benign | -0.212 | Destabilizing | 0.921 | D | 0.52 | neutral | N | 0.468912485 | 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.