Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3059 | 9400;9401;9402 | chr2:178768144;178768143;178768142 | chr2:179632871;179632870;179632869 |
| N2AB | 3059 | 9400;9401;9402 | chr2:178768144;178768143;178768142 | chr2:179632871;179632870;179632869 |
| N2A | 3059 | 9400;9401;9402 | chr2:178768144;178768143;178768142 | chr2:179632871;179632870;179632869 |
| N2B | 3013 | 9262;9263;9264 | chr2:178768144;178768143;178768142 | chr2:179632871;179632870;179632869 |
| Novex-1 | 3013 | 9262;9263;9264 | chr2:178768144;178768143;178768142 | chr2:179632871;179632870;179632869 |
| Novex-2 | 3013 | 9262;9263;9264 | chr2:178768144;178768143;178768142 | chr2:179632871;179632870;179632869 |
| Novex-3 | 3059 | 9400;9401;9402 | chr2:178768144;178768143;178768142 | chr2:179632871;179632870;179632869 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/Q | None | None | 0.89 | N | 0.381 | 0.326 | 0.219573609325 | gnomAD-4.0.0 | 1.59075E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.0217E-05 |
| E/V | rs727504501  |
0.011 | 0.942 | N | 0.545 | 0.508 | 0.62999039529 | gnomAD-2.1.1 | 5.32E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 6.54846E-04 | None | 3.27E-05 | None | 0 | 0 | 0 |
| E/V | rs727504501 |
0.011 | 0.942 | N | 0.545 | 0.508 | 0.62999039529 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 5.76923E-04 | None | 0 | 0 | 0 | 0 | 0 |
| E/V | rs727504501 |
0.011 | 0.942 | N | 0.545 | 0.508 | 0.62999039529 | gnomAD-4.0.0 | 2.78823E-05 | None | None | None | None | N | None | 0 | 1.66733E-05 | None | 0 | 6.9147E-04 | None | 0 | 0 | 0 | 1.09784E-05 | 1.92049E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.5412 | ambiguous | 0.4245 | ambiguous | -0.508 | Destabilizing | 0.698 | D | 0.451 | neutral | D | 0.533919147 | None | None | N |
| E/C | 0.979 | likely_pathogenic | 0.9765 | pathogenic | -0.197 | Destabilizing | 0.998 | D | 0.685 | prob.neutral | None | None | None | None | N |
| E/D | 0.6656 | likely_pathogenic | 0.5349 | ambiguous | -0.421 | Destabilizing | 0.014 | N | 0.216 | neutral | N | 0.513865876 | None | None | N |
| E/F | 0.9702 | likely_pathogenic | 0.958 | pathogenic | -0.188 | Destabilizing | 0.998 | D | 0.624 | neutral | None | None | None | None | N |
| E/G | 0.8114 | likely_pathogenic | 0.7219 | pathogenic | -0.747 | Destabilizing | 0.822 | D | 0.449 | neutral | D | 0.62625688 | None | None | N |
| E/H | 0.9099 | likely_pathogenic | 0.8621 | pathogenic | -0.013 | Destabilizing | 0.994 | D | 0.399 | neutral | None | None | None | None | N |
| E/I | 0.8005 | likely_pathogenic | 0.7504 | pathogenic | 0.102 | Stabilizing | 0.978 | D | 0.637 | neutral | None | None | None | None | N |
| E/K | 0.738 | likely_pathogenic | 0.6178 | pathogenic | 0.13 | Stabilizing | 0.014 | N | 0.293 | neutral | N | 0.503874826 | None | None | N |
| E/L | 0.886 | likely_pathogenic | 0.8268 | pathogenic | 0.102 | Stabilizing | 0.956 | D | 0.62 | neutral | None | None | None | None | N |
| E/M | 0.8556 | likely_pathogenic | 0.808 | pathogenic | 0.215 | Stabilizing | 0.998 | D | 0.556 | neutral | None | None | None | None | N |
| E/N | 0.8462 | likely_pathogenic | 0.7601 | pathogenic | -0.287 | Destabilizing | 0.956 | D | 0.388 | neutral | None | None | None | None | N |
| E/P | 0.9917 | likely_pathogenic | 0.985 | pathogenic | -0.081 | Destabilizing | 0.978 | D | 0.461 | neutral | None | None | None | None | N |
| E/Q | 0.4166 | ambiguous | 0.328 | benign | -0.216 | Destabilizing | 0.89 | D | 0.381 | neutral | N | 0.510616611 | None | None | N |
| E/R | 0.8092 | likely_pathogenic | 0.7193 | pathogenic | 0.407 | Stabilizing | 0.915 | D | 0.408 | neutral | None | None | None | None | N |
| E/S | 0.6556 | likely_pathogenic | 0.5431 | ambiguous | -0.467 | Destabilizing | 0.754 | D | 0.389 | neutral | None | None | None | None | N |
| E/T | 0.6095 | likely_pathogenic | 0.5212 | ambiguous | -0.267 | Destabilizing | 0.956 | D | 0.423 | neutral | None | None | None | None | N |
| E/V | 0.5841 | likely_pathogenic | 0.511 | ambiguous | -0.081 | Destabilizing | 0.942 | D | 0.545 | neutral | N | 0.509405367 | None | None | N |
| E/W | 0.9951 | likely_pathogenic | 0.9924 | pathogenic | 0.031 | Stabilizing | 0.998 | D | 0.694 | prob.neutral | None | None | None | None | N |
| E/Y | 0.9586 | likely_pathogenic | 0.9412 | pathogenic | 0.065 | Stabilizing | 0.993 | D | 0.561 | neutral | 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.