Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26967 | 81124;81125;81126 | chr2:178565233;178565232;178565231 | chr2:179429960;179429959;179429958 |
| N2AB | 25326 | 76201;76202;76203 | chr2:178565233;178565232;178565231 | chr2:179429960;179429959;179429958 |
| N2A | 24399 | 73420;73421;73422 | chr2:178565233;178565232;178565231 | chr2:179429960;179429959;179429958 |
| N2B | 17902 | 53929;53930;53931 | chr2:178565233;178565232;178565231 | chr2:179429960;179429959;179429958 |
| Novex-1 | 18027 | 54304;54305;54306 | chr2:178565233;178565232;178565231 | chr2:179429960;179429959;179429958 |
| Novex-2 | 18094 | 54505;54506;54507 | chr2:178565233;178565232;178565231 | chr2:179429960;179429959;179429958 |
| 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 | rs753639960  |
-2.136 | 0.104 | N | 0.549 | 0.447 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| V/A | rs753639960 |
-2.136 | 0.104 | N | 0.549 | 0.447 | None | gnomAD-4.0.0 | 4.77496E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71762E-06 | 0 | 3.02499E-05 |
| V/I | rs1257567608 |
None | None | N | 0.259 | 0.091 | 0.149567049428 | gnomAD-4.0.0 | 3.18332E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41663E-04 | 2.85883E-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 | 0.8552 | likely_pathogenic | 0.8268 | pathogenic | -1.692 | Destabilizing | 0.104 | N | 0.549 | neutral | N | 0.492997623 | None | None | N |
| V/C | 0.9224 | likely_pathogenic | 0.9088 | pathogenic | -0.95 | Destabilizing | 0.968 | D | 0.741 | deleterious | None | None | None | None | N |
| V/D | 0.9929 | likely_pathogenic | 0.9935 | pathogenic | -2.425 | Highly Destabilizing | 0.667 | D | 0.816 | deleterious | D | 0.527573518 | None | None | N |
| V/E | 0.9865 | likely_pathogenic | 0.9872 | pathogenic | -2.095 | Highly Destabilizing | 0.726 | D | 0.784 | deleterious | None | None | None | None | N |
| V/F | 0.409 | ambiguous | 0.3621 | ambiguous | -0.909 | Destabilizing | 0.497 | N | 0.753 | deleterious | N | 0.508201816 | None | None | N |
| V/G | 0.9297 | likely_pathogenic | 0.9269 | pathogenic | -2.323 | Highly Destabilizing | 0.667 | D | 0.801 | deleterious | D | 0.527573518 | None | None | N |
| V/H | 0.9899 | likely_pathogenic | 0.989 | pathogenic | -2.428 | Highly Destabilizing | 0.968 | D | 0.807 | deleterious | None | None | None | None | N |
| V/I | 0.0581 | likely_benign | 0.0555 | benign | 0.133 | Stabilizing | None | N | 0.259 | neutral | N | 0.470660638 | None | None | N |
| V/K | 0.9856 | likely_pathogenic | 0.9862 | pathogenic | -1.094 | Destabilizing | 0.726 | D | 0.785 | deleterious | None | None | None | None | N |
| V/L | 0.2356 | likely_benign | 0.2096 | benign | 0.133 | Stabilizing | None | N | 0.289 | neutral | N | 0.472411998 | None | None | N |
| V/M | 0.3404 | ambiguous | 0.2965 | benign | -0.086 | Destabilizing | 0.567 | D | 0.662 | neutral | None | None | None | None | N |
| V/N | 0.9737 | likely_pathogenic | 0.9693 | pathogenic | -1.777 | Destabilizing | 0.89 | D | 0.808 | deleterious | None | None | None | None | N |
| V/P | 0.9819 | likely_pathogenic | 0.984 | pathogenic | -0.454 | Destabilizing | 0.89 | D | 0.788 | deleterious | None | None | None | None | N |
| V/Q | 0.9837 | likely_pathogenic | 0.9823 | pathogenic | -1.352 | Destabilizing | 0.89 | D | 0.777 | deleterious | None | None | None | None | N |
| V/R | 0.9759 | likely_pathogenic | 0.9767 | pathogenic | -1.474 | Destabilizing | 0.726 | D | 0.812 | deleterious | None | None | None | None | N |
| V/S | 0.9572 | likely_pathogenic | 0.9482 | pathogenic | -2.306 | Highly Destabilizing | 0.726 | D | 0.779 | deleterious | None | None | None | None | N |
| V/T | 0.91 | likely_pathogenic | 0.8881 | pathogenic | -1.799 | Destabilizing | 0.272 | N | 0.576 | neutral | None | None | None | None | N |
| V/W | 0.979 | likely_pathogenic | 0.9776 | pathogenic | -1.493 | Destabilizing | 0.968 | D | 0.807 | deleterious | None | None | None | None | N |
| V/Y | 0.9308 | likely_pathogenic | 0.9226 | pathogenic | -1.063 | Destabilizing | 0.726 | D | 0.756 | 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.