Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2168 | 6727;6728;6729 | chr2:178775362;178775361;178775360 | chr2:179640089;179640088;179640087 |
| N2AB | 2168 | 6727;6728;6729 | chr2:178775362;178775361;178775360 | chr2:179640089;179640088;179640087 |
| N2A | 2168 | 6727;6728;6729 | chr2:178775362;178775361;178775360 | chr2:179640089;179640088;179640087 |
| N2B | 2122 | 6589;6590;6591 | chr2:178775362;178775361;178775360 | chr2:179640089;179640088;179640087 |
| Novex-1 | 2122 | 6589;6590;6591 | chr2:178775362;178775361;178775360 | chr2:179640089;179640088;179640087 |
| Novex-2 | 2122 | 6589;6590;6591 | chr2:178775362;178775361;178775360 | chr2:179640089;179640088;179640087 |
| Novex-3 | 2168 | 6727;6728;6729 | chr2:178775362;178775361;178775360 | chr2:179640089;179640088;179640087 |
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/D | None | None | 0.991 | D | 0.669 | 0.916 | 0.941643032232 | gnomAD-4.0.0 | 1.59086E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85662E-06 | 0 | 0 |
| V/I | rs764454260  |
-0.826 | 0.046 | D | 0.467 | 0.574 | 0.705795206982 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/I | rs764454260 |
-0.826 | 0.046 | D | 0.467 | 0.574 | 0.705795206982 | gnomAD-4.0.0 | 1.59089E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 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 | 0.8884 | likely_pathogenic | 0.9098 | pathogenic | -1.678 | Destabilizing | 0.046 | N | 0.455 | neutral | D | 0.756654841 | None | None | N |
| V/C | 0.9723 | likely_pathogenic | 0.9738 | pathogenic | -1.555 | Destabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | N |
| V/D | 0.9983 | likely_pathogenic | 0.9985 | pathogenic | -1.773 | Destabilizing | 0.991 | D | 0.669 | neutral | D | 0.787909761 | None | None | N |
| V/E | 0.9919 | likely_pathogenic | 0.9925 | pathogenic | -1.739 | Destabilizing | 0.986 | D | 0.607 | neutral | None | None | None | None | N |
| V/F | 0.9709 | likely_pathogenic | 0.977 | pathogenic | -1.33 | Destabilizing | 0.982 | D | 0.604 | neutral | D | 0.787827417 | None | None | N |
| V/G | 0.943 | likely_pathogenic | 0.9557 | pathogenic | -2.004 | Highly Destabilizing | 0.964 | D | 0.636 | neutral | D | 0.787909761 | None | None | N |
| V/H | 0.9984 | likely_pathogenic | 0.9985 | pathogenic | -1.443 | Destabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| V/I | 0.1439 | likely_benign | 0.1581 | benign | -0.863 | Destabilizing | 0.046 | N | 0.467 | neutral | D | 0.602634401 | None | None | N |
| V/K | 0.9957 | likely_pathogenic | 0.9961 | pathogenic | -1.247 | Destabilizing | 0.986 | D | 0.611 | neutral | None | None | None | None | N |
| V/L | 0.8412 | likely_pathogenic | 0.8762 | pathogenic | -0.863 | Destabilizing | 0.76 | D | 0.542 | neutral | D | 0.736271248 | None | None | N |
| V/M | 0.8907 | likely_pathogenic | 0.913 | pathogenic | -0.934 | Destabilizing | 0.986 | D | 0.609 | neutral | None | None | None | None | N |
| V/N | 0.9898 | likely_pathogenic | 0.9915 | pathogenic | -1.204 | Destabilizing | 0.993 | D | 0.679 | prob.neutral | None | None | None | None | N |
| V/P | 0.9878 | likely_pathogenic | 0.9894 | pathogenic | -1.103 | Destabilizing | 0.993 | D | 0.633 | neutral | None | None | None | None | N |
| V/Q | 0.992 | likely_pathogenic | 0.9928 | pathogenic | -1.383 | Destabilizing | 0.993 | D | 0.643 | neutral | None | None | None | None | N |
| V/R | 0.9925 | likely_pathogenic | 0.9929 | pathogenic | -0.8 | Destabilizing | 0.993 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/S | 0.9507 | likely_pathogenic | 0.9602 | pathogenic | -1.778 | Destabilizing | 0.973 | D | 0.585 | neutral | None | None | None | None | N |
| V/T | 0.8887 | likely_pathogenic | 0.9067 | pathogenic | -1.634 | Destabilizing | 0.953 | D | 0.565 | neutral | None | None | None | None | N |
| V/W | 0.9996 | likely_pathogenic | 0.9996 | pathogenic | -1.485 | Destabilizing | 0.999 | D | 0.647 | neutral | None | None | None | None | N |
| V/Y | 0.9971 | likely_pathogenic | 0.9974 | pathogenic | -1.17 | Destabilizing | 0.998 | D | 0.603 | neutral | 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.