Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25104 | 75535;75536;75537 | chr2:178570822;178570821;178570820 | chr2:179435549;179435548;179435547 |
| N2AB | 23463 | 70612;70613;70614 | chr2:178570822;178570821;178570820 | chr2:179435549;179435548;179435547 |
| N2A | 22536 | 67831;67832;67833 | chr2:178570822;178570821;178570820 | chr2:179435549;179435548;179435547 |
| N2B | 16039 | 48340;48341;48342 | chr2:178570822;178570821;178570820 | chr2:179435549;179435548;179435547 |
| Novex-1 | 16164 | 48715;48716;48717 | chr2:178570822;178570821;178570820 | chr2:179435549;179435548;179435547 |
| Novex-2 | 16231 | 48916;48917;48918 | chr2:178570822;178570821;178570820 | chr2:179435549;179435548;179435547 |
| 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/V | rs534319705  |
0.363 | 1.0 | N | 0.755 | 0.478 | 0.324986149311 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93274E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | rs534319705 |
0.363 | 1.0 | N | 0.755 | 0.478 | 0.324986149311 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| D/V | rs534319705 |
0.363 | 1.0 | N | 0.755 | 0.478 | 0.324986149311 | gnomAD-4.0.0 | 1.53758E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.91305E-04 | 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 | 0.8858 | likely_pathogenic | 0.8039 | pathogenic | -0.31 | Destabilizing | 1.0 | D | 0.725 | deleterious | N | 0.450662004 | None | None | N |
| D/C | 0.9907 | likely_pathogenic | 0.9826 | pathogenic | 0.057 | Stabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| D/E | 0.8372 | likely_pathogenic | 0.763 | pathogenic | -0.354 | Destabilizing | 0.999 | D | 0.447 | neutral | N | 0.508885379 | None | None | N |
| D/F | 0.9854 | likely_pathogenic | 0.9771 | pathogenic | -0.355 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| D/G | 0.8902 | likely_pathogenic | 0.8119 | pathogenic | -0.501 | Destabilizing | 1.0 | D | 0.78 | deleterious | N | 0.476198998 | None | None | N |
| D/H | 0.9611 | likely_pathogenic | 0.9334 | pathogenic | -0.266 | Destabilizing | 1.0 | D | 0.889 | deleterious | N | 0.467377588 | None | None | N |
| D/I | 0.9739 | likely_pathogenic | 0.9564 | pathogenic | 0.145 | Stabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| D/K | 0.9774 | likely_pathogenic | 0.9618 | pathogenic | 0.174 | Stabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| D/L | 0.9521 | likely_pathogenic | 0.9254 | pathogenic | 0.145 | Stabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| D/M | 0.9845 | likely_pathogenic | 0.9748 | pathogenic | 0.348 | Stabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| D/N | 0.6591 | likely_pathogenic | 0.5413 | ambiguous | -0.02 | Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.474846326 | None | None | N |
| D/P | 0.9855 | likely_pathogenic | 0.9762 | pathogenic | 0.015 | Stabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| D/Q | 0.9695 | likely_pathogenic | 0.9468 | pathogenic | -0.001 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| D/R | 0.9786 | likely_pathogenic | 0.9658 | pathogenic | 0.314 | Stabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| D/S | 0.8251 | likely_pathogenic | 0.7271 | pathogenic | -0.147 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| D/T | 0.951 | likely_pathogenic | 0.9126 | pathogenic | -0.006 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| D/V | 0.9213 | likely_pathogenic | 0.8733 | pathogenic | 0.015 | Stabilizing | 1.0 | D | 0.755 | deleterious | N | 0.503711002 | None | None | N |
| D/W | 0.9947 | likely_pathogenic | 0.9909 | pathogenic | -0.264 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| D/Y | 0.8829 | likely_pathogenic | 0.8245 | pathogenic | -0.139 | Destabilizing | 1.0 | D | 0.801 | deleterious | N | 0.50497845 | 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.