Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1340 | 4243;4244;4245 | chr2:178779064;178779063;178779062 | chr2:179643791;179643790;179643789 |
| N2AB | 1340 | 4243;4244;4245 | chr2:178779064;178779063;178779062 | chr2:179643791;179643790;179643789 |
| N2A | 1340 | 4243;4244;4245 | chr2:178779064;178779063;178779062 | chr2:179643791;179643790;179643789 |
| N2B | 1294 | 4105;4106;4107 | chr2:178779064;178779063;178779062 | chr2:179643791;179643790;179643789 |
| Novex-1 | 1294 | 4105;4106;4107 | chr2:178779064;178779063;178779062 | chr2:179643791;179643790;179643789 |
| Novex-2 | 1294 | 4105;4106;4107 | chr2:178779064;178779063;178779062 | chr2:179643791;179643790;179643789 |
| Novex-3 | 1340 | 4243;4244;4245 | chr2:178779064;178779063;178779062 | chr2:179643791;179643790;179643789 |
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/G | rs780035210  |
-0.644 | None | N | 0.161 | 0.404 | 0.218845423259 | gnomAD-2.1.1 | 1.6E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.54E-05 | 0 |
| D/G | rs780035210 |
-0.644 | None | N | 0.161 | 0.404 | 0.218845423259 | 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 |
| D/G | rs780035210 |
-0.644 | None | N | 0.161 | 0.404 | 0.218845423259 | gnomAD-4.0.0 | 1.05336E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44071E-05 | 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 | 0.3533 | ambiguous | 0.4144 | ambiguous | -0.201 | Destabilizing | 0.027 | N | 0.432 | neutral | N | 0.460837066 | None | None | N |
| D/C | 0.8936 | likely_pathogenic | 0.9159 | pathogenic | 0.007 | Stabilizing | 0.935 | D | 0.567 | neutral | None | None | None | None | N |
| D/E | 0.2107 | likely_benign | 0.242 | benign | -0.252 | Destabilizing | None | N | 0.102 | neutral | N | 0.38568994 | None | None | N |
| D/F | 0.8476 | likely_pathogenic | 0.8846 | pathogenic | -0.114 | Destabilizing | 0.791 | D | 0.561 | neutral | None | None | None | None | N |
| D/G | 0.453 | ambiguous | 0.5116 | ambiguous | -0.403 | Destabilizing | None | N | 0.161 | neutral | N | 0.459741873 | None | None | N |
| D/H | 0.5285 | ambiguous | 0.6079 | pathogenic | 0.063 | Stabilizing | 0.484 | N | 0.448 | neutral | N | 0.457160037 | None | None | N |
| D/I | 0.6227 | likely_pathogenic | 0.6866 | pathogenic | 0.28 | Stabilizing | 0.555 | D | 0.571 | neutral | None | None | None | None | N |
| D/K | 0.7406 | likely_pathogenic | 0.7981 | pathogenic | 0.325 | Stabilizing | 0.035 | N | 0.415 | neutral | None | None | None | None | N |
| D/L | 0.6713 | likely_pathogenic | 0.7325 | pathogenic | 0.28 | Stabilizing | 0.149 | N | 0.536 | neutral | None | None | None | None | N |
| D/M | 0.8455 | likely_pathogenic | 0.8819 | pathogenic | 0.333 | Stabilizing | 0.935 | D | 0.537 | neutral | None | None | None | None | N |
| D/N | 0.204 | likely_benign | 0.244 | benign | 0.028 | Stabilizing | 0.117 | N | 0.375 | neutral | N | 0.445187935 | None | None | N |
| D/P | 0.9877 | likely_pathogenic | 0.9901 | pathogenic | 0.142 | Stabilizing | 0.262 | N | 0.419 | neutral | None | None | None | None | N |
| D/Q | 0.5711 | likely_pathogenic | 0.6453 | pathogenic | 0.069 | Stabilizing | 0.081 | N | 0.325 | neutral | None | None | None | None | N |
| D/R | 0.7421 | likely_pathogenic | 0.7982 | pathogenic | 0.506 | Stabilizing | 0.081 | N | 0.509 | neutral | None | None | None | None | N |
| D/S | 0.2622 | likely_benign | 0.3105 | benign | -0.088 | Destabilizing | 0.035 | N | 0.379 | neutral | None | None | None | None | N |
| D/T | 0.4519 | ambiguous | 0.5161 | ambiguous | 0.07 | Stabilizing | 0.149 | N | 0.365 | neutral | None | None | None | None | N |
| D/V | 0.3938 | ambiguous | 0.4595 | ambiguous | 0.142 | Stabilizing | 0.117 | N | 0.507 | neutral | N | 0.385728246 | None | None | N |
| D/W | 0.9735 | likely_pathogenic | 0.9795 | pathogenic | 0.009 | Stabilizing | 0.935 | D | 0.593 | neutral | None | None | None | None | N |
| D/Y | 0.4905 | ambiguous | 0.5544 | ambiguous | 0.124 | Stabilizing | 0.741 | D | 0.562 | neutral | N | 0.453540635 | 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.