Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28546 | 85861;85862;85863 | chr2:178560496;178560495;178560494 | chr2:179425223;179425222;179425221 |
| N2AB | 26905 | 80938;80939;80940 | chr2:178560496;178560495;178560494 | chr2:179425223;179425222;179425221 |
| N2A | 25978 | 78157;78158;78159 | chr2:178560496;178560495;178560494 | chr2:179425223;179425222;179425221 |
| N2B | 19481 | 58666;58667;58668 | chr2:178560496;178560495;178560494 | chr2:179425223;179425222;179425221 |
| Novex-1 | 19606 | 59041;59042;59043 | chr2:178560496;178560495;178560494 | chr2:179425223;179425222;179425221 |
| Novex-2 | 19673 | 59242;59243;59244 | chr2:178560496;178560495;178560494 | chr2:179425223;179425222;179425221 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs771897496  |
0.536 | None | N | 0.306 | 0.096 | 0.162503812791 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| D/N | rs771897496 |
0.536 | None | N | 0.306 | 0.096 | 0.162503812791 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| D/N | rs771897496 |
0.536 | None | N | 0.306 | 0.096 | 0.162503812791 | gnomAD-4.0.0 | 3.84715E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.0235E-05 | 0 |
| D/V | None | None | 0.001 | N | 0.505 | 0.39 | 0.546174653742 | gnomAD-4.0.0 | 1.59289E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86058E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4952 | ambiguous | 0.4055 | ambiguous | -0.172 | Destabilizing | 0.061 | N | 0.643 | neutral | N | 0.511486619 | None | None | N |
| D/C | 0.855 | likely_pathogenic | 0.8203 | pathogenic | -0.037 | Destabilizing | 0.934 | D | 0.79 | deleterious | None | None | None | None | N |
| D/E | 0.5894 | likely_pathogenic | 0.4898 | ambiguous | -0.223 | Destabilizing | 0.061 | N | 0.613 | neutral | N | 0.508734316 | None | None | N |
| D/F | 0.784 | likely_pathogenic | 0.7238 | pathogenic | -0.153 | Destabilizing | 0.378 | N | 0.737 | deleterious | None | None | None | None | N |
| D/G | 0.6399 | likely_pathogenic | 0.5725 | pathogenic | -0.332 | Destabilizing | 0.061 | N | 0.653 | prob.neutral | N | 0.484599465 | None | None | N |
| D/H | 0.5008 | ambiguous | 0.4346 | ambiguous | 0.22 | Stabilizing | 0.002 | N | 0.529 | neutral | N | 0.48060022 | None | None | N |
| D/I | 0.7035 | likely_pathogenic | 0.5919 | pathogenic | 0.194 | Stabilizing | 0.233 | N | 0.692 | prob.delet. | None | None | None | None | N |
| D/K | 0.8652 | likely_pathogenic | 0.8187 | pathogenic | 0.356 | Stabilizing | 0.08 | N | 0.696 | prob.delet. | None | None | None | None | N |
| D/L | 0.6335 | likely_pathogenic | 0.5378 | ambiguous | 0.194 | Stabilizing | 0.08 | N | 0.677 | prob.neutral | None | None | None | None | N |
| D/M | 0.8757 | likely_pathogenic | 0.8194 | pathogenic | 0.178 | Stabilizing | 0.823 | D | 0.699 | prob.delet. | None | None | None | None | N |
| D/N | 0.1557 | likely_benign | 0.1367 | benign | 0.099 | Stabilizing | None | N | 0.306 | neutral | N | 0.445416343 | None | None | N |
| D/P | 0.7925 | likely_pathogenic | 0.7396 | pathogenic | 0.093 | Stabilizing | 0.552 | D | 0.67 | prob.neutral | None | None | None | None | N |
| D/Q | 0.803 | likely_pathogenic | 0.7305 | pathogenic | 0.122 | Stabilizing | 0.378 | N | 0.577 | neutral | None | None | None | None | N |
| D/R | 0.8755 | likely_pathogenic | 0.8305 | pathogenic | 0.569 | Stabilizing | 0.378 | N | 0.764 | deleterious | None | None | None | None | N |
| D/S | 0.3016 | likely_benign | 0.2465 | benign | -0.012 | Destabilizing | 0.08 | N | 0.583 | neutral | None | None | None | None | N |
| D/T | 0.6117 | likely_pathogenic | 0.5532 | ambiguous | 0.116 | Stabilizing | 0.08 | N | 0.723 | deleterious | None | None | None | None | N |
| D/V | 0.5464 | ambiguous | 0.4419 | ambiguous | 0.093 | Stabilizing | 0.001 | N | 0.505 | neutral | N | 0.520100413 | None | None | N |
| D/W | 0.9558 | likely_pathogenic | 0.9416 | pathogenic | -0.051 | Destabilizing | 0.934 | D | 0.833 | deleterious | None | None | None | None | N |
| D/Y | 0.3244 | likely_benign | 0.2786 | benign | 0.08 | Stabilizing | 0.314 | N | 0.732 | deleterious | N | 0.514046922 | 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.