Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2693 | 8302;8303;8304 | chr2:178771250;178771249;178771248 | chr2:179635977;179635976;179635975 |
| N2AB | 2693 | 8302;8303;8304 | chr2:178771250;178771249;178771248 | chr2:179635977;179635976;179635975 |
| N2A | 2693 | 8302;8303;8304 | chr2:178771250;178771249;178771248 | chr2:179635977;179635976;179635975 |
| N2B | 2647 | 8164;8165;8166 | chr2:178771250;178771249;178771248 | chr2:179635977;179635976;179635975 |
| Novex-1 | 2647 | 8164;8165;8166 | chr2:178771250;178771249;178771248 | chr2:179635977;179635976;179635975 |
| Novex-2 | 2647 | 8164;8165;8166 | chr2:178771250;178771249;178771248 | chr2:179635977;179635976;179635975 |
| Novex-3 | 2693 | 8302;8303;8304 | chr2:178771250;178771249;178771248 | chr2:179635977;179635976;179635975 |
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/A | rs780868304  |
-1.938 | 0.977 | N | 0.612 | 0.372 | 0.572657343838 | gnomAD-2.1.1 | 7.96E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.76E-05 | 0 |
| V/A | rs780868304 |
-1.938 | 0.977 | N | 0.612 | 0.372 | 0.572657343838 | gnomAD-4.0.0 | 1.505E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.88854E-05 | 0 | 1.65579E-05 |
| V/M | rs1349732520 |
-0.584 | 0.993 | D | 0.81 | 0.525 | 0.674745919162 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| V/M | rs1349732520 |
-0.584 | 0.993 | D | 0.81 | 0.525 | 0.674745919162 | gnomAD-4.0.0 | 1.59064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.775E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4675 | ambiguous | 0.4724 | ambiguous | -1.551 | Destabilizing | 0.977 | D | 0.612 | neutral | N | 0.478730331 | None | None | N |
| V/C | 0.9353 | likely_pathogenic | 0.9415 | pathogenic | -1.168 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| V/D | 0.8671 | likely_pathogenic | 0.8808 | pathogenic | -1.006 | Destabilizing | 0.999 | D | 0.881 | deleterious | None | None | None | None | N |
| V/E | 0.8173 | likely_pathogenic | 0.8457 | pathogenic | -0.965 | Destabilizing | 0.999 | D | 0.869 | deleterious | D | 0.706327368 | None | None | N |
| V/F | 0.53 | ambiguous | 0.5587 | ambiguous | -1.094 | Destabilizing | 0.995 | D | 0.868 | deleterious | None | None | None | None | N |
| V/G | 0.614 | likely_pathogenic | 0.6148 | pathogenic | -1.916 | Destabilizing | 0.999 | D | 0.875 | deleterious | D | 0.668529607 | None | None | N |
| V/H | 0.952 | likely_pathogenic | 0.9596 | pathogenic | -1.394 | Destabilizing | 1.0 | D | 0.89 | deleterious | None | None | None | None | N |
| V/I | 0.1233 | likely_benign | 0.1375 | benign | -0.634 | Destabilizing | 0.15 | N | 0.267 | neutral | None | None | None | None | N |
| V/K | 0.9095 | likely_pathogenic | 0.9201 | pathogenic | -1.111 | Destabilizing | 0.998 | D | 0.871 | deleterious | None | None | None | None | N |
| V/L | 0.5135 | ambiguous | 0.5764 | pathogenic | -0.634 | Destabilizing | 0.898 | D | 0.627 | neutral | D | 0.5452067 | None | None | N |
| V/M | 0.4421 | ambiguous | 0.4915 | ambiguous | -0.593 | Destabilizing | 0.993 | D | 0.81 | deleterious | D | 0.596379727 | None | None | N |
| V/N | 0.7848 | likely_pathogenic | 0.8049 | pathogenic | -0.958 | Destabilizing | 0.999 | D | 0.901 | deleterious | None | None | None | None | N |
| V/P | 0.9777 | likely_pathogenic | 0.9804 | pathogenic | -0.905 | Destabilizing | 0.999 | D | 0.871 | deleterious | None | None | None | None | N |
| V/Q | 0.8788 | likely_pathogenic | 0.8957 | pathogenic | -1.063 | Destabilizing | 0.999 | D | 0.894 | deleterious | None | None | None | None | N |
| V/R | 0.8699 | likely_pathogenic | 0.8835 | pathogenic | -0.715 | Destabilizing | 0.999 | D | 0.895 | deleterious | None | None | None | None | N |
| V/S | 0.6581 | likely_pathogenic | 0.6662 | pathogenic | -1.625 | Destabilizing | 0.998 | D | 0.861 | deleterious | None | None | None | None | N |
| V/T | 0.4439 | ambiguous | 0.4672 | ambiguous | -1.459 | Destabilizing | 0.983 | D | 0.709 | prob.delet. | None | None | None | None | N |
| V/W | 0.9759 | likely_pathogenic | 0.9824 | pathogenic | -1.27 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| V/Y | 0.8949 | likely_pathogenic | 0.9083 | pathogenic | -0.963 | Destabilizing | 0.999 | D | 0.867 | deleterious | 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.