Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1361 | 4306;4307;4308 | chr2:178779001;178779000;178778999 | chr2:179643728;179643727;179643726 |
| N2AB | 1361 | 4306;4307;4308 | chr2:178779001;178779000;178778999 | chr2:179643728;179643727;179643726 |
| N2A | 1361 | 4306;4307;4308 | chr2:178779001;178779000;178778999 | chr2:179643728;179643727;179643726 |
| N2B | 1315 | 4168;4169;4170 | chr2:178779001;178779000;178778999 | chr2:179643728;179643727;179643726 |
| Novex-1 | 1315 | 4168;4169;4170 | chr2:178779001;178779000;178778999 | chr2:179643728;179643727;179643726 |
| Novex-2 | 1315 | 4168;4169;4170 | chr2:178779001;178779000;178778999 | chr2:179643728;179643727;179643726 |
| Novex-3 | 1361 | 4306;4307;4308 | chr2:178779001;178779000;178778999 | chr2:179643728;179643727;179643726 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs145308734  |
-0.663 | 0.817 | N | 0.309 | 0.194 | None | gnomAD-2.1.1 | 6.38E-05 | None | None | None | None | N | None | 4.01E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.3224E-04 | 0 |
| I/L | rs145308734 |
-0.663 | 0.817 | N | 0.309 | 0.194 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.82E-05 | 0 | 0 |
| I/L | rs145308734 |
-0.663 | 0.817 | N | 0.309 | 0.194 | None | gnomAD-4.0.0 | 1.93325E-04 | None | None | None | None | N | None | 4.00598E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.45773E-04 | 1.09801E-05 | 2.88065E-04 |
| I/V | rs145308734 |
-0.909 | 0.219 | N | 0.203 | 0.167 | 0.595645824669 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs145308734 |
-0.909 | 0.219 | N | 0.203 | 0.167 | 0.595645824669 | gnomAD-4.0.0 | 1.36824E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.5208E-05 | None | 0 | 0 | 8.99337E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9773 | likely_pathogenic | 0.9723 | pathogenic | -1.435 | Destabilizing | 0.964 | D | 0.556 | neutral | None | None | None | None | N |
| I/C | 0.9858 | likely_pathogenic | 0.9868 | pathogenic | -0.991 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| I/D | 0.9971 | likely_pathogenic | 0.9954 | pathogenic | -0.364 | Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | N |
| I/E | 0.9929 | likely_pathogenic | 0.9892 | pathogenic | -0.374 | Destabilizing | 0.999 | D | 0.762 | deleterious | None | None | None | None | N |
| I/F | 0.7594 | likely_pathogenic | 0.7577 | pathogenic | -1.087 | Destabilizing | 0.997 | D | 0.585 | neutral | N | 0.503411518 | None | None | N |
| I/G | 0.9961 | likely_pathogenic | 0.9953 | pathogenic | -1.726 | Destabilizing | 0.999 | D | 0.738 | prob.delet. | None | None | None | None | N |
| I/H | 0.9913 | likely_pathogenic | 0.9885 | pathogenic | -0.906 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| I/K | 0.9887 | likely_pathogenic | 0.9842 | pathogenic | -0.702 | Destabilizing | 0.999 | D | 0.765 | deleterious | None | None | None | None | N |
| I/L | 0.523 | ambiguous | 0.5426 | ambiguous | -0.73 | Destabilizing | 0.817 | D | 0.309 | neutral | N | 0.430965665 | None | None | N |
| I/M | 0.6098 | likely_pathogenic | 0.611 | pathogenic | -0.61 | Destabilizing | 0.997 | D | 0.615 | neutral | N | 0.48059115 | None | None | N |
| I/N | 0.9556 | likely_pathogenic | 0.9357 | pathogenic | -0.498 | Destabilizing | 0.999 | D | 0.779 | deleterious | N | 0.402600275 | None | None | N |
| I/P | 0.9951 | likely_pathogenic | 0.9944 | pathogenic | -0.932 | Destabilizing | 0.999 | D | 0.777 | deleterious | None | None | None | None | N |
| I/Q | 0.9912 | likely_pathogenic | 0.9873 | pathogenic | -0.682 | Destabilizing | 0.999 | D | 0.772 | deleterious | None | None | None | None | N |
| I/R | 0.9781 | likely_pathogenic | 0.9708 | pathogenic | -0.192 | Destabilizing | 0.999 | D | 0.778 | deleterious | None | None | None | None | N |
| I/S | 0.9709 | likely_pathogenic | 0.9619 | pathogenic | -1.212 | Destabilizing | 0.997 | D | 0.697 | prob.neutral | N | 0.472577145 | None | None | N |
| I/T | 0.9393 | likely_pathogenic | 0.9287 | pathogenic | -1.1 | Destabilizing | 0.98 | D | 0.559 | neutral | N | 0.435771048 | None | None | N |
| I/V | 0.2315 | likely_benign | 0.2471 | benign | -0.932 | Destabilizing | 0.219 | N | 0.203 | neutral | N | 0.43905366 | None | None | N |
| I/W | 0.9914 | likely_pathogenic | 0.9895 | pathogenic | -1.078 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| I/Y | 0.9493 | likely_pathogenic | 0.9408 | pathogenic | -0.837 | Destabilizing | 0.999 | D | 0.716 | 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.