Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26279 | 79060;79061;79062 | chr2:178567297;178567296;178567295 | chr2:179432024;179432023;179432022 |
| N2AB | 24638 | 74137;74138;74139 | chr2:178567297;178567296;178567295 | chr2:179432024;179432023;179432022 |
| N2A | 23711 | 71356;71357;71358 | chr2:178567297;178567296;178567295 | chr2:179432024;179432023;179432022 |
| N2B | 17214 | 51865;51866;51867 | chr2:178567297;178567296;178567295 | chr2:179432024;179432023;179432022 |
| Novex-1 | 17339 | 52240;52241;52242 | chr2:178567297;178567296;178567295 | chr2:179432024;179432023;179432022 |
| Novex-2 | 17406 | 52441;52442;52443 | chr2:178567297;178567296;178567295 | chr2:179432024;179432023;179432022 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | None | None | 0.001 | N | 0.107 | 0.105 | 0.412064437402 | gnomAD-4.0.0 | 6.87419E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01434E-07 | 0 | 0 |
| V/L | rs878904723  |
-0.104 | 0.08 | D | 0.326 | 0.187 | 0.293502639404 | gnomAD-2.1.1 | 4.14E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.09E-06 | 0 |
| V/L | rs878904723 |
-0.104 | 0.08 | D | 0.326 | 0.187 | 0.293502639404 | gnomAD-4.0.0 | 1.78729E-05 | None | None | None | None | N | None | 6.06171E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.16344E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6296 | likely_pathogenic | 0.6097 | pathogenic | -2.186 | Highly Destabilizing | 0.001 | N | 0.143 | neutral | N | 0.501579057 | None | None | N |
| V/C | 0.7956 | likely_pathogenic | 0.7787 | pathogenic | -1.731 | Destabilizing | 0.901 | D | 0.704 | prob.neutral | None | None | None | None | N |
| V/D | 0.9921 | likely_pathogenic | 0.9929 | pathogenic | -3.195 | Highly Destabilizing | 0.901 | D | 0.792 | deleterious | None | None | None | None | N |
| V/E | 0.979 | likely_pathogenic | 0.9811 | pathogenic | -2.873 | Highly Destabilizing | 0.491 | N | 0.752 | deleterious | D | 0.538327389 | None | None | N |
| V/F | 0.4 | ambiguous | 0.3819 | ambiguous | -1.251 | Destabilizing | 0.002 | N | 0.317 | neutral | None | None | None | None | N |
| V/G | 0.8293 | likely_pathogenic | 0.8212 | pathogenic | -2.816 | Highly Destabilizing | 0.326 | N | 0.715 | prob.delet. | N | 0.502283463 | None | None | N |
| V/H | 0.9825 | likely_pathogenic | 0.981 | pathogenic | -2.811 | Highly Destabilizing | 0.991 | D | 0.742 | deleterious | None | None | None | None | N |
| V/I | 0.0769 | likely_benign | 0.0774 | benign | -0.366 | Destabilizing | 0.001 | N | 0.107 | neutral | N | 0.452270531 | None | None | N |
| V/K | 0.9779 | likely_pathogenic | 0.9791 | pathogenic | -1.838 | Destabilizing | 0.561 | D | 0.756 | deleterious | None | None | None | None | N |
| V/L | 0.3179 | likely_benign | 0.3007 | benign | -0.366 | Destabilizing | 0.08 | N | 0.326 | neutral | D | 0.528189655 | None | None | N |
| V/M | 0.3108 | likely_benign | 0.2974 | benign | -0.606 | Destabilizing | 0.818 | D | 0.632 | neutral | None | None | None | None | N |
| V/N | 0.9623 | likely_pathogenic | 0.9627 | pathogenic | -2.496 | Highly Destabilizing | 0.901 | D | 0.762 | deleterious | None | None | None | None | N |
| V/P | 0.9897 | likely_pathogenic | 0.9901 | pathogenic | -0.952 | Destabilizing | 0.901 | D | 0.742 | deleterious | None | None | None | None | N |
| V/Q | 0.9601 | likely_pathogenic | 0.9612 | pathogenic | -2.135 | Highly Destabilizing | 0.901 | D | 0.737 | prob.delet. | None | None | None | None | N |
| V/R | 0.9608 | likely_pathogenic | 0.962 | pathogenic | -1.975 | Destabilizing | 0.901 | D | 0.759 | deleterious | None | None | None | None | N |
| V/S | 0.8734 | likely_pathogenic | 0.8689 | pathogenic | -3.043 | Highly Destabilizing | 0.39 | N | 0.682 | prob.neutral | None | None | None | None | N |
| V/T | 0.7614 | likely_pathogenic | 0.7558 | pathogenic | -2.552 | Highly Destabilizing | 0.561 | D | 0.528 | neutral | None | None | None | None | N |
| V/W | 0.9774 | likely_pathogenic | 0.9726 | pathogenic | -1.874 | Destabilizing | 0.991 | D | 0.729 | prob.delet. | None | None | None | None | N |
| V/Y | 0.9187 | likely_pathogenic | 0.9117 | pathogenic | -1.483 | Destabilizing | 0.39 | N | 0.717 | prob.delet. | None | None | 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.