Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2147 | 6664;6665;6666 | chr2:178775425;178775424;178775423 | chr2:179640152;179640151;179640150 |
| N2AB | 2147 | 6664;6665;6666 | chr2:178775425;178775424;178775423 | chr2:179640152;179640151;179640150 |
| N2A | 2147 | 6664;6665;6666 | chr2:178775425;178775424;178775423 | chr2:179640152;179640151;179640150 |
| N2B | 2101 | 6526;6527;6528 | chr2:178775425;178775424;178775423 | chr2:179640152;179640151;179640150 |
| Novex-1 | 2101 | 6526;6527;6528 | chr2:178775425;178775424;178775423 | chr2:179640152;179640151;179640150 |
| Novex-2 | 2101 | 6526;6527;6528 | chr2:178775425;178775424;178775423 | chr2:179640152;179640151;179640150 |
| Novex-3 | 2147 | 6664;6665;6666 | chr2:178775425;178775424;178775423 | chr2:179640152;179640151;179640150 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs528516043  |
-1.18 | 0.41 | D | 0.8 | 0.369 | 0.32580497728 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 0 |
| A/T | rs528516043 |
-1.18 | 0.41 | D | 0.8 | 0.369 | 0.32580497728 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/T | rs528516043 |
-1.18 | 0.41 | D | 0.8 | 0.369 | 0.32580497728 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| A/T | rs528516043 |
-1.18 | 0.41 | D | 0.8 | 0.369 | 0.32580497728 | gnomAD-4.0.0 | 2.47826E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.38984E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7241 | likely_pathogenic | 0.7186 | pathogenic | -1.158 | Destabilizing | 0.98 | D | 0.853 | deleterious | None | None | None | None | N |
| A/D | 0.9099 | likely_pathogenic | 0.9217 | pathogenic | -1.195 | Destabilizing | 0.709 | D | 0.869 | deleterious | D | 0.547434258 | None | None | N |
| A/E | 0.9223 | likely_pathogenic | 0.9276 | pathogenic | -1.201 | Destabilizing | 0.764 | D | 0.853 | deleterious | None | None | None | None | N |
| A/F | 0.9066 | likely_pathogenic | 0.9002 | pathogenic | -1.089 | Destabilizing | 0.929 | D | 0.877 | deleterious | None | None | None | None | N |
| A/G | 0.1881 | likely_benign | 0.1991 | benign | -1.268 | Destabilizing | 0.41 | N | 0.803 | deleterious | N | 0.337287285 | None | None | N |
| A/H | 0.9538 | likely_pathogenic | 0.9563 | pathogenic | -1.38 | Destabilizing | 0.98 | D | 0.862 | deleterious | None | None | None | None | N |
| A/I | 0.9343 | likely_pathogenic | 0.938 | pathogenic | -0.365 | Destabilizing | 0.866 | D | 0.867 | deleterious | None | None | None | None | N |
| A/K | 0.9872 | likely_pathogenic | 0.9877 | pathogenic | -1.133 | Destabilizing | 0.764 | D | 0.854 | deleterious | None | None | None | None | N |
| A/L | 0.7823 | likely_pathogenic | 0.776 | pathogenic | -0.365 | Destabilizing | 0.648 | D | 0.821 | deleterious | None | None | None | None | N |
| A/M | 0.8036 | likely_pathogenic | 0.8011 | pathogenic | -0.388 | Destabilizing | 0.993 | D | 0.839 | deleterious | None | None | None | None | N |
| A/N | 0.8402 | likely_pathogenic | 0.8527 | pathogenic | -0.962 | Destabilizing | 0.764 | D | 0.881 | deleterious | None | None | None | None | N |
| A/P | 0.9942 | likely_pathogenic | 0.9947 | pathogenic | -0.531 | Destabilizing | 0.83 | D | 0.867 | deleterious | D | 0.647184484 | None | None | N |
| A/Q | 0.9038 | likely_pathogenic | 0.9059 | pathogenic | -1.094 | Destabilizing | 0.866 | D | 0.859 | deleterious | None | None | None | None | N |
| A/R | 0.9688 | likely_pathogenic | 0.9697 | pathogenic | -0.849 | Destabilizing | 0.866 | D | 0.868 | deleterious | None | None | None | None | N |
| A/S | 0.1034 | likely_benign | 0.1115 | benign | -1.392 | Destabilizing | 0.01 | N | 0.576 | neutral | D | 0.562860929 | None | None | N |
| A/T | 0.3687 | ambiguous | 0.3958 | ambiguous | -1.292 | Destabilizing | 0.41 | N | 0.8 | deleterious | D | 0.606436544 | None | None | N |
| A/V | 0.7279 | likely_pathogenic | 0.7434 | pathogenic | -0.531 | Destabilizing | 0.581 | D | 0.812 | deleterious | D | 0.6470722 | None | None | N |
| A/W | 0.9905 | likely_pathogenic | 0.9907 | pathogenic | -1.427 | Destabilizing | 0.993 | D | 0.842 | deleterious | None | None | None | None | N |
| A/Y | 0.9489 | likely_pathogenic | 0.9465 | pathogenic | -1.002 | Destabilizing | 0.98 | D | 0.88 | 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.