Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16681 | 50266;50267;50268 | chr2:178612484;178612483;178612482 | chr2:179477211;179477210;179477209 |
| N2AB | 15040 | 45343;45344;45345 | chr2:178612484;178612483;178612482 | chr2:179477211;179477210;179477209 |
| N2A | 14113 | 42562;42563;42564 | chr2:178612484;178612483;178612482 | chr2:179477211;179477210;179477209 |
| N2B | 7616 | 23071;23072;23073 | chr2:178612484;178612483;178612482 | chr2:179477211;179477210;179477209 |
| Novex-1 | 7741 | 23446;23447;23448 | chr2:178612484;178612483;178612482 | chr2:179477211;179477210;179477209 |
| Novex-2 | 7808 | 23647;23648;23649 | chr2:178612484;178612483;178612482 | chr2:179477211;179477210;179477209 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/P | None | None | 1.0 | D | 0.762 | 0.553 | 0.435479573448 | gnomAD-4.0.0 | 1.36975E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79984E-06 | 0 | 0 |
| S/T | rs771522078  |
-0.524 | 0.999 | N | 0.589 | 0.219 | 0.245660935333 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.12E-06 | 0 |
| S/T | rs771522078 |
-0.524 | 0.999 | N | 0.589 | 0.219 | 0.245660935333 | gnomAD-4.0.0 | 6.84876E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99922E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2724 | likely_benign | 0.3349 | benign | -0.503 | Destabilizing | 0.997 | D | 0.587 | neutral | N | 0.466510375 | None | None | I |
| S/C | 0.3656 | ambiguous | 0.4205 | ambiguous | -0.322 | Destabilizing | 1.0 | D | 0.752 | deleterious | D | 0.5662771 | None | None | I |
| S/D | 0.9558 | likely_pathogenic | 0.979 | pathogenic | -0.319 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | I |
| S/E | 0.9542 | likely_pathogenic | 0.9764 | pathogenic | -0.387 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | I |
| S/F | 0.6448 | likely_pathogenic | 0.7964 | pathogenic | -0.979 | Destabilizing | 1.0 | D | 0.801 | deleterious | D | 0.646659564 | None | None | I |
| S/G | 0.5414 | ambiguous | 0.6633 | pathogenic | -0.664 | Destabilizing | 0.999 | D | 0.575 | neutral | None | None | None | None | I |
| S/H | 0.7894 | likely_pathogenic | 0.8636 | pathogenic | -1.249 | Destabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | I |
| S/I | 0.7063 | likely_pathogenic | 0.8379 | pathogenic | -0.199 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | I |
| S/K | 0.9839 | likely_pathogenic | 0.9915 | pathogenic | -0.625 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | I |
| S/L | 0.3608 | ambiguous | 0.5203 | ambiguous | -0.199 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | I |
| S/M | 0.582 | likely_pathogenic | 0.7011 | pathogenic | 0.247 | Stabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | I |
| S/N | 0.7109 | likely_pathogenic | 0.8097 | pathogenic | -0.444 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | I |
| S/P | 0.99 | likely_pathogenic | 0.996 | pathogenic | -0.27 | Destabilizing | 1.0 | D | 0.762 | deleterious | D | 0.721818393 | None | None | I |
| S/Q | 0.9075 | likely_pathogenic | 0.9346 | pathogenic | -0.745 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | I |
| S/R | 0.9762 | likely_pathogenic | 0.988 | pathogenic | -0.393 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| S/T | 0.376 | ambiguous | 0.4827 | ambiguous | -0.498 | Destabilizing | 0.999 | D | 0.589 | neutral | N | 0.509771223 | None | None | I |
| S/V | 0.6788 | likely_pathogenic | 0.8028 | pathogenic | -0.27 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | I |
| S/W | 0.853 | likely_pathogenic | 0.9239 | pathogenic | -0.951 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | I |
| S/Y | 0.6309 | likely_pathogenic | 0.779 | pathogenic | -0.682 | Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.721818393 | 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.