Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23998 | 72217;72218;72219 | chr2:178574140;178574139;178574138 | chr2:179438867;179438866;179438865 |
| N2AB | 22357 | 67294;67295;67296 | chr2:178574140;178574139;178574138 | chr2:179438867;179438866;179438865 |
| N2A | 21430 | 64513;64514;64515 | chr2:178574140;178574139;178574138 | chr2:179438867;179438866;179438865 |
| N2B | 14933 | 45022;45023;45024 | chr2:178574140;178574139;178574138 | chr2:179438867;179438866;179438865 |
| Novex-1 | 15058 | 45397;45398;45399 | chr2:178574140;178574139;178574138 | chr2:179438867;179438866;179438865 |
| Novex-2 | 15125 | 45598;45599;45600 | chr2:178574140;178574139;178574138 | chr2:179438867;179438866;179438865 |
| 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 | None | None | 1.0 | D | 0.83 | 0.528 | 0.499727662827 | gnomAD-4.0.0 | 1.59171E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43295E-05 | 0 |
| R/H | rs10164753  |
-2.876 | 1.0 | D | 0.807 | 0.517 | None | gnomAD-2.1.1 | 7.63289E-02 | None | None | None | None | I | None | 7.93283E-02 | 1.99468E-01 | None | 2.97308E-02 | 2.77378E-02 | None | 1.81583E-01 | None | 5.71143E-02 | 3.21738E-02 | 6.15514E-02 |
| R/H | rs10164753 |
-2.876 | 1.0 | D | 0.807 | 0.517 | None | gnomAD-3.1.2 | 6.35507E-02 | None | None | None | None | I | None | 7.94774E-02 | 1.57184E-01 | 4.94505E-02 | 2.96659E-02 | 2.43997E-02 | None | 5.88124E-02 | 7.91139E-02 | 3.06083E-02 | 1.76556E-01 | 5.64054E-02 |
| R/H | rs10164753 |
-2.876 | 1.0 | D | 0.807 | 0.517 | None | 1000 genomes | 9.78435E-02 | None | None | None | None | I | None | 8.77E-02 | 1.542E-01 | None | None | 2.58E-02 | 4.67E-02 | None | None | None | 1.984E-01 | None |
| R/H | rs10164753 |
-2.876 | 1.0 | D | 0.807 | 0.517 | None | gnomAD-4.0.0 | 4.89895E-02 | None | None | None | None | I | None | 8.08775E-02 | 1.86829E-01 | None | 2.93621E-02 | 1.51116E-02 | None | 5.8852E-02 | 5.08755E-02 | 3.13507E-02 | 1.73483E-01 | 5.32845E-02 |
| R/L | None | None | 1.0 | N | 0.723 | 0.646 | 0.463758542814 | gnomAD-4.0.0 | 6.84299E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99567E-07 | 0 | 0 |
| R/P | None | None | 1.0 | D | 0.805 | 0.645 | 0.52360052443 | gnomAD-4.0.0 | 6.84299E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99567E-07 | 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 | 0.9758 | likely_pathogenic | 0.9801 | pathogenic | -1.963 | Destabilizing | 0.999 | D | 0.619 | neutral | None | None | None | None | I |
| R/C | 0.5247 | ambiguous | 0.5665 | pathogenic | -1.853 | Destabilizing | 1.0 | D | 0.83 | deleterious | D | 0.526586014 | None | None | I |
| R/D | 0.9967 | likely_pathogenic | 0.9972 | pathogenic | -1.011 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| R/E | 0.9543 | likely_pathogenic | 0.9643 | pathogenic | -0.786 | Destabilizing | 0.999 | D | 0.67 | neutral | None | None | None | None | I |
| R/F | 0.9799 | likely_pathogenic | 0.9825 | pathogenic | -1.123 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | I |
| R/G | 0.9675 | likely_pathogenic | 0.9739 | pathogenic | -2.311 | Highly Destabilizing | 1.0 | D | 0.723 | prob.delet. | D | 0.548791645 | None | None | I |
| R/H | 0.2735 | likely_benign | 0.3634 | ambiguous | -2.113 | Highly Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.526079035 | None | None | I |
| R/I | 0.9561 | likely_pathogenic | 0.961 | pathogenic | -0.948 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | I |
| R/K | 0.5249 | ambiguous | 0.5626 | ambiguous | -1.236 | Destabilizing | 0.998 | D | 0.647 | neutral | None | None | None | None | I |
| R/L | 0.9053 | likely_pathogenic | 0.9236 | pathogenic | -0.948 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.505390659 | None | None | I |
| R/M | 0.953 | likely_pathogenic | 0.9626 | pathogenic | -1.486 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | I |
| R/N | 0.9815 | likely_pathogenic | 0.9852 | pathogenic | -1.325 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| R/P | 0.9986 | likely_pathogenic | 0.9986 | pathogenic | -1.276 | Destabilizing | 1.0 | D | 0.805 | deleterious | D | 0.549045135 | None | None | I |
| R/Q | 0.3985 | ambiguous | 0.4577 | ambiguous | -1.142 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | I |
| R/S | 0.9753 | likely_pathogenic | 0.982 | pathogenic | -2.186 | Highly Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.503313517 | None | None | I |
| R/T | 0.9685 | likely_pathogenic | 0.9747 | pathogenic | -1.746 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | I |
| R/V | 0.96 | likely_pathogenic | 0.9647 | pathogenic | -1.276 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | I |
| R/W | 0.7359 | likely_pathogenic | 0.7844 | pathogenic | -0.664 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | I |
| R/Y | 0.9205 | likely_pathogenic | 0.937 | pathogenic | -0.526 | Destabilizing | 1.0 | D | 0.832 | 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.