Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16182 | 48769;48770;48771 | chr2:178615401;178615400;178615399 | chr2:179480128;179480127;179480126 |
| N2AB | 14541 | 43846;43847;43848 | chr2:178615401;178615400;178615399 | chr2:179480128;179480127;179480126 |
| N2A | 13614 | 41065;41066;41067 | chr2:178615401;178615400;178615399 | chr2:179480128;179480127;179480126 |
| N2B | 7117 | 21574;21575;21576 | chr2:178615401;178615400;178615399 | chr2:179480128;179480127;179480126 |
| Novex-1 | 7242 | 21949;21950;21951 | chr2:178615401;178615400;178615399 | chr2:179480128;179480127;179480126 |
| Novex-2 | 7309 | 22150;22151;22152 | chr2:178615401;178615400;178615399 | chr2:179480128;179480127;179480126 |
| 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/A | rs762913484  |
0.078 | 1.0 | D | 0.758 | 0.522 | None | gnomAD-2.1.1 | 2.14E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.91E-05 | 0 |
| D/A | rs762913484 |
0.078 | 1.0 | D | 0.758 | 0.522 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/A | rs762913484 |
0.078 | 1.0 | D | 0.758 | 0.522 | None | gnomAD-4.0.0 | 1.30229E-05 | None | None | None | None | N | None | 1.33704E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.52663E-05 | 0 | 3.20544E-05 |
| D/V | None | None | 1.0 | D | 0.753 | 0.586 | 0.775662873616 | gnomAD-4.0.0 | 1.36928E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87266E-05 | 0 | 0 | 1.16004E-05 | 0 |
| D/Y | rs766675813 |
-0.435 | 1.0 | D | 0.696 | 0.496 | 0.819937569887 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| D/Y | rs766675813 |
-0.435 | 1.0 | D | 0.696 | 0.496 | 0.819937569887 | gnomAD-4.0.0 | 1.59356E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77701E-05 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.917 | likely_pathogenic | 0.8999 | pathogenic | -0.054 | Destabilizing | 1.0 | D | 0.758 | deleterious | D | 0.60315861 | None | None | N |
| D/C | 0.9798 | likely_pathogenic | 0.9778 | pathogenic | 0.202 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| D/E | 0.9094 | likely_pathogenic | 0.902 | pathogenic | -0.734 | Destabilizing | 1.0 | D | 0.446 | neutral | D | 0.604699399 | None | None | N |
| D/F | 0.9899 | likely_pathogenic | 0.9881 | pathogenic | -0.432 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| D/G | 0.8906 | likely_pathogenic | 0.8639 | pathogenic | -0.315 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | D | 0.641941311 | None | None | N |
| D/H | 0.9472 | likely_pathogenic | 0.9346 | pathogenic | -0.854 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | D | 0.62668449 | None | None | N |
| D/I | 0.9824 | likely_pathogenic | 0.9787 | pathogenic | 0.591 | Stabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| D/K | 0.9825 | likely_pathogenic | 0.9767 | pathogenic | 0.07 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| D/L | 0.9763 | likely_pathogenic | 0.9718 | pathogenic | 0.591 | Stabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| D/M | 0.9924 | likely_pathogenic | 0.9907 | pathogenic | 1.028 | Stabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| D/N | 0.3487 | ambiguous | 0.3576 | ambiguous | -0.186 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | N | 0.483566687 | None | None | N |
| D/P | 0.9819 | likely_pathogenic | 0.9799 | pathogenic | 0.402 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| D/Q | 0.978 | likely_pathogenic | 0.9719 | pathogenic | -0.111 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| D/R | 0.9802 | likely_pathogenic | 0.9721 | pathogenic | -0.084 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| D/S | 0.6546 | likely_pathogenic | 0.6256 | pathogenic | -0.325 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| D/T | 0.8548 | likely_pathogenic | 0.8218 | pathogenic | -0.117 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| D/V | 0.9541 | likely_pathogenic | 0.9397 | pathogenic | 0.402 | Stabilizing | 1.0 | D | 0.753 | deleterious | D | 0.634753253 | None | None | N |
| D/W | 0.9982 | likely_pathogenic | 0.9973 | pathogenic | -0.534 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| D/Y | 0.9256 | likely_pathogenic | 0.9045 | pathogenic | -0.248 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | D | 0.762947732 | 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.