Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24580 | 73963;73964;73965 | chr2:178572394;178572393;178572392 | chr2:179437121;179437120;179437119 |
| N2AB | 22939 | 69040;69041;69042 | chr2:178572394;178572393;178572392 | chr2:179437121;179437120;179437119 |
| N2A | 22012 | 66259;66260;66261 | chr2:178572394;178572393;178572392 | chr2:179437121;179437120;179437119 |
| N2B | 15515 | 46768;46769;46770 | chr2:178572394;178572393;178572392 | chr2:179437121;179437120;179437119 |
| Novex-1 | 15640 | 47143;47144;47145 | chr2:178572394;178572393;178572392 | chr2:179437121;179437120;179437119 |
| Novex-2 | 15707 | 47344;47345;47346 | chr2:178572394;178572393;178572392 | chr2:179437121;179437120;179437119 |
| Novex-3 | None | None | chr2:None | chr2:None |
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 | rs141005138  |
-2.188 | 0.004 | N | 0.355 | 0.334 | None | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 1.29282E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs141005138 |
-2.188 | 0.004 | N | 0.355 | 0.334 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs141005138 |
-2.188 | 0.004 | N | 0.355 | 0.334 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/A | rs141005138 |
-2.188 | 0.004 | N | 0.355 | 0.334 | None | gnomAD-4.0.0 | 6.19933E-06 | None | None | None | None | N | None | 9.33085E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54394E-06 | 0 | 0 |
| V/I | rs765510494 |
-0.078 | None | N | 0.179 | 0.106 | 0.319114376414 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| V/I | rs765510494 |
-0.078 | None | N | 0.179 | 0.106 | 0.319114376414 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 | 0.5108 | ambiguous | 0.4751 | ambiguous | -1.991 | Destabilizing | 0.004 | N | 0.355 | neutral | N | 0.487545072 | None | None | N |
| V/C | 0.9131 | likely_pathogenic | 0.9114 | pathogenic | -1.521 | Destabilizing | 0.976 | D | 0.796 | deleterious | None | None | None | None | N |
| V/D | 0.9901 | likely_pathogenic | 0.9886 | pathogenic | -2.638 | Highly Destabilizing | 0.999 | D | 0.85 | deleterious | None | None | None | None | N |
| V/E | 0.9737 | likely_pathogenic | 0.971 | pathogenic | -2.378 | Highly Destabilizing | 0.98 | D | 0.801 | deleterious | D | 0.536857861 | None | None | N |
| V/F | 0.6904 | likely_pathogenic | 0.6253 | pathogenic | -1.208 | Destabilizing | 0.963 | D | 0.801 | deleterious | None | None | None | None | N |
| V/G | 0.8571 | likely_pathogenic | 0.8256 | pathogenic | -2.572 | Highly Destabilizing | 0.66 | D | 0.797 | deleterious | D | 0.548214166 | None | None | N |
| V/H | 0.9927 | likely_pathogenic | 0.9912 | pathogenic | -2.421 | Highly Destabilizing | 0.994 | D | 0.853 | deleterious | None | None | None | None | N |
| V/I | 0.0717 | likely_benign | 0.0747 | benign | -0.351 | Destabilizing | None | N | 0.179 | neutral | N | 0.443197183 | None | None | N |
| V/K | 0.9878 | likely_pathogenic | 0.9867 | pathogenic | -1.679 | Destabilizing | 0.993 | D | 0.809 | deleterious | None | None | None | None | N |
| V/L | 0.4335 | ambiguous | 0.3942 | ambiguous | -0.351 | Destabilizing | 0.014 | N | 0.481 | neutral | N | 0.505722935 | None | None | N |
| V/M | 0.4521 | ambiguous | 0.3992 | ambiguous | -0.402 | Destabilizing | 0.949 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/N | 0.9689 | likely_pathogenic | 0.968 | pathogenic | -2.098 | Highly Destabilizing | 0.978 | D | 0.847 | deleterious | None | None | None | None | N |
| V/P | 0.964 | likely_pathogenic | 0.9621 | pathogenic | -0.872 | Destabilizing | 0.978 | D | 0.832 | deleterious | None | None | None | None | N |
| V/Q | 0.978 | likely_pathogenic | 0.9751 | pathogenic | -1.86 | Destabilizing | 0.995 | D | 0.833 | deleterious | None | None | None | None | N |
| V/R | 0.9808 | likely_pathogenic | 0.9784 | pathogenic | -1.664 | Destabilizing | 0.998 | D | 0.851 | deleterious | None | None | None | None | N |
| V/S | 0.8805 | likely_pathogenic | 0.8662 | pathogenic | -2.723 | Highly Destabilizing | 0.436 | N | 0.779 | deleterious | None | None | None | None | N |
| V/T | 0.6557 | likely_pathogenic | 0.6241 | pathogenic | -2.298 | Highly Destabilizing | 0.384 | N | 0.722 | prob.delet. | None | None | None | None | N |
| V/W | 0.9914 | likely_pathogenic | 0.9876 | pathogenic | -1.764 | Destabilizing | 0.998 | D | 0.829 | deleterious | None | None | None | None | N |
| V/Y | 0.9654 | likely_pathogenic | 0.9559 | pathogenic | -1.332 | Destabilizing | 0.953 | D | 0.796 | 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.