Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1899 | 5920;5921;5922 | chr2:178776169;178776168;178776167 | chr2:179640896;179640895;179640894 |
| N2AB | 1899 | 5920;5921;5922 | chr2:178776169;178776168;178776167 | chr2:179640896;179640895;179640894 |
| N2A | 1899 | 5920;5921;5922 | chr2:178776169;178776168;178776167 | chr2:179640896;179640895;179640894 |
| N2B | 1853 | 5782;5783;5784 | chr2:178776169;178776168;178776167 | chr2:179640896;179640895;179640894 |
| Novex-1 | 1853 | 5782;5783;5784 | chr2:178776169;178776168;178776167 | chr2:179640896;179640895;179640894 |
| Novex-2 | 1853 | 5782;5783;5784 | chr2:178776169;178776168;178776167 | chr2:179640896;179640895;179640894 |
| Novex-3 | 1899 | 5920;5921;5922 | chr2:178776169;178776168;178776167 | chr2:179640896;179640895;179640894 |
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/T | None | None | 1.0 | D | 0.823 | 0.798 | 0.880129815424 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.75482E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs878986033  |
-1.644 | 0.993 | D | 0.405 | 0.421 | 0.779112364068 | gnomAD-2.1.1 | 1.59E-05 | None | None | None | None | N | None | 1.84593E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.63239E-04 |
| I/V | rs878986033 |
-1.644 | 0.993 | D | 0.405 | 0.421 | 0.779112364068 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs878986033 |
-1.644 | 0.993 | D | 0.405 | 0.421 | 0.779112364068 | gnomAD-4.0.0 | 4.33691E-06 | None | None | None | None | N | None | 8.00726E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60036E-05 |
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 | 0.97 | likely_pathogenic | 0.9773 | pathogenic | -3.067 | Highly Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| I/C | 0.9859 | likely_pathogenic | 0.9894 | pathogenic | -2.558 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| I/D | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -3.581 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| I/E | 0.9986 | likely_pathogenic | 0.9988 | pathogenic | -3.269 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| I/F | 0.7048 | likely_pathogenic | 0.7557 | pathogenic | -1.837 | Destabilizing | 1.0 | D | 0.814 | deleterious | D | 0.586049474 | None | None | N |
| I/G | 0.9985 | likely_pathogenic | 0.9987 | pathogenic | -3.707 | Highly Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| I/H | 0.9976 | likely_pathogenic | 0.998 | pathogenic | -3.187 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| I/K | 0.9974 | likely_pathogenic | 0.9978 | pathogenic | -2.474 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| I/L | 0.4438 | ambiguous | 0.4853 | ambiguous | -1.155 | Destabilizing | 0.993 | D | 0.427 | neutral | D | 0.578163287 | None | None | N |
| I/M | 0.3849 | ambiguous | 0.4231 | ambiguous | -1.302 | Destabilizing | 1.0 | D | 0.757 | deleterious | D | 0.649306137 | None | None | N |
| I/N | 0.9935 | likely_pathogenic | 0.9946 | pathogenic | -3.103 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | D | 0.734173838 | None | None | N |
| I/P | 0.9992 | likely_pathogenic | 0.9993 | pathogenic | -1.781 | Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| I/Q | 0.9976 | likely_pathogenic | 0.9981 | pathogenic | -2.809 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| I/R | 0.9953 | likely_pathogenic | 0.996 | pathogenic | -2.332 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| I/S | 0.9879 | likely_pathogenic | 0.9903 | pathogenic | -3.82 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | D | 0.755498919 | None | None | N |
| I/T | 0.9621 | likely_pathogenic | 0.972 | pathogenic | -3.334 | Highly Destabilizing | 1.0 | D | 0.823 | deleterious | D | 0.734359651 | None | None | N |
| I/V | 0.182 | likely_benign | 0.2069 | benign | -1.781 | Destabilizing | 0.993 | D | 0.405 | neutral | D | 0.547180467 | None | None | N |
| I/W | 0.9939 | likely_pathogenic | 0.9952 | pathogenic | -2.225 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| I/Y | 0.979 | likely_pathogenic | 0.9834 | pathogenic | -2.02 | Highly Destabilizing | 1.0 | D | 0.821 | 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.