Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2084 | 6475;6476;6477 | chr2:178775614;178775613;178775612 | chr2:179640341;179640340;179640339 |
| N2AB | 2084 | 6475;6476;6477 | chr2:178775614;178775613;178775612 | chr2:179640341;179640340;179640339 |
| N2A | 2084 | 6475;6476;6477 | chr2:178775614;178775613;178775612 | chr2:179640341;179640340;179640339 |
| N2B | 2038 | 6337;6338;6339 | chr2:178775614;178775613;178775612 | chr2:179640341;179640340;179640339 |
| Novex-1 | 2038 | 6337;6338;6339 | chr2:178775614;178775613;178775612 | chr2:179640341;179640340;179640339 |
| Novex-2 | 2038 | 6337;6338;6339 | chr2:178775614;178775613;178775612 | chr2:179640341;179640340;179640339 |
| Novex-3 | 2084 | 6475;6476;6477 | chr2:178775614;178775613;178775612 | chr2:179640341;179640340;179640339 |
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 | 0.731 | 0.732 | 0.785726413069 | gnomAD-4.0.0 | 1.59059E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85654E-06 | 0 | 0 |
| I/V | rs369388581  |
-1.034 | 0.993 | D | 0.367 | 0.364 | None | gnomAD-2.1.1 | 7.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 0 |
| I/V | rs369388581 |
-1.034 | 0.993 | D | 0.367 | 0.364 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/V | rs369388581 |
-1.034 | 0.993 | D | 0.367 | 0.364 | None | gnomAD-4.0.0 | 5.57613E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.77959E-06 | 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 | 0.9745 | likely_pathogenic | 0.9783 | pathogenic | -2.036 | Highly Destabilizing | 0.999 | D | 0.548 | neutral | None | None | None | None | I |
| I/C | 0.9882 | likely_pathogenic | 0.9911 | pathogenic | -1.382 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| I/D | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -2.139 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| I/E | 0.9985 | likely_pathogenic | 0.9986 | pathogenic | -1.901 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | I |
| I/F | 0.8959 | likely_pathogenic | 0.9157 | pathogenic | -1.075 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | D | 0.533253912 | None | None | I |
| I/G | 0.997 | likely_pathogenic | 0.9974 | pathogenic | -2.585 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | I |
| I/H | 0.9987 | likely_pathogenic | 0.9991 | pathogenic | -2.15 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | I |
| I/K | 0.9976 | likely_pathogenic | 0.9978 | pathogenic | -1.372 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | I |
| I/L | 0.3288 | likely_benign | 0.3144 | benign | -0.463 | Destabilizing | 0.993 | D | 0.415 | neutral | N | 0.406228012 | None | None | I |
| I/M | 0.4336 | ambiguous | 0.4321 | ambiguous | -0.596 | Destabilizing | 1.0 | D | 0.743 | deleterious | D | 0.531168005 | None | None | I |
| I/N | 0.991 | likely_pathogenic | 0.9926 | pathogenic | -1.724 | Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.604858144 | None | None | I |
| I/P | 0.9595 | likely_pathogenic | 0.9743 | pathogenic | -0.966 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | I |
| I/Q | 0.9967 | likely_pathogenic | 0.9972 | pathogenic | -1.534 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | I |
| I/R | 0.997 | likely_pathogenic | 0.9974 | pathogenic | -1.296 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | I |
| I/S | 0.9872 | likely_pathogenic | 0.99 | pathogenic | -2.425 | Highly Destabilizing | 1.0 | D | 0.778 | deleterious | D | 0.527067876 | None | None | I |
| I/T | 0.9863 | likely_pathogenic | 0.9875 | pathogenic | -2.036 | Highly Destabilizing | 1.0 | D | 0.731 | prob.delet. | D | 0.53129734 | None | None | I |
| I/V | 0.4123 | ambiguous | 0.4247 | ambiguous | -0.966 | Destabilizing | 0.993 | D | 0.367 | neutral | D | 0.532075644 | None | None | I |
| I/W | 0.9986 | likely_pathogenic | 0.999 | pathogenic | -1.459 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| I/Y | 0.9948 | likely_pathogenic | 0.9961 | pathogenic | -1.104 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | I |
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.