Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21113 | 63562;63563;63564 | chr2:178588070;178588069;178588068 | chr2:179452797;179452796;179452795 |
| N2AB | 19472 | 58639;58640;58641 | chr2:178588070;178588069;178588068 | chr2:179452797;179452796;179452795 |
| N2A | 18545 | 55858;55859;55860 | chr2:178588070;178588069;178588068 | chr2:179452797;179452796;179452795 |
| N2B | 12048 | 36367;36368;36369 | chr2:178588070;178588069;178588068 | chr2:179452797;179452796;179452795 |
| Novex-1 | 12173 | 36742;36743;36744 | chr2:178588070;178588069;178588068 | chr2:179452797;179452796;179452795 |
| Novex-2 | 12240 | 36943;36944;36945 | chr2:178588070;178588069;178588068 | chr2:179452797;179452796;179452795 |
| 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/A | rs748932912  |
-0.632 | 0.09 | N | 0.425 | 0.253 | 0.300784259202 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 0 |
| D/A | rs748932912 |
-0.632 | 0.09 | N | 0.425 | 0.253 | 0.300784259202 | gnomAD-4.0.0 | 6.16069E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29837E-06 | 0 | 3.31466E-05 |
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 | 0.0957 | likely_benign | 0.1013 | benign | -0.519 | Destabilizing | 0.09 | N | 0.425 | neutral | N | 0.480739638 | None | None | N |
| D/C | 0.4493 | ambiguous | 0.4525 | ambiguous | -0.173 | Destabilizing | 0.981 | D | 0.451 | neutral | None | None | None | None | N |
| D/E | 0.0733 | likely_benign | 0.0755 | benign | -0.396 | Destabilizing | 0.001 | N | 0.269 | neutral | N | 0.423883491 | None | None | N |
| D/F | 0.3875 | ambiguous | 0.4206 | ambiguous | -0.402 | Destabilizing | 0.932 | D | 0.452 | neutral | None | None | None | None | N |
| D/G | 0.1005 | likely_benign | 0.1054 | benign | -0.726 | Destabilizing | 0.001 | N | 0.349 | neutral | N | 0.426830582 | None | None | N |
| D/H | 0.1759 | likely_benign | 0.1783 | benign | -0.235 | Destabilizing | 0.627 | D | 0.333 | neutral | N | 0.476672973 | None | None | N |
| D/I | 0.2102 | likely_benign | 0.2193 | benign | -0.015 | Destabilizing | 0.818 | D | 0.461 | neutral | None | None | None | None | N |
| D/K | 0.1684 | likely_benign | 0.175 | benign | -0.016 | Destabilizing | 0.241 | N | 0.395 | neutral | None | None | None | None | N |
| D/L | 0.2125 | likely_benign | 0.2205 | benign | -0.015 | Destabilizing | 0.388 | N | 0.451 | neutral | None | None | None | None | N |
| D/M | 0.3478 | ambiguous | 0.3678 | ambiguous | 0.152 | Stabilizing | 0.981 | D | 0.437 | neutral | None | None | None | None | N |
| D/N | 0.0847 | likely_benign | 0.0863 | benign | -0.268 | Destabilizing | 0.001 | N | 0.355 | neutral | N | 0.458094852 | None | None | N |
| D/P | 0.3966 | ambiguous | 0.4388 | ambiguous | -0.162 | Destabilizing | 0.818 | D | 0.339 | neutral | None | None | None | None | N |
| D/Q | 0.1502 | likely_benign | 0.1572 | benign | -0.238 | Destabilizing | 0.241 | N | 0.351 | neutral | None | None | None | None | N |
| D/R | 0.2099 | likely_benign | 0.2177 | benign | 0.236 | Stabilizing | 0.69 | D | 0.437 | neutral | None | None | None | None | N |
| D/S | 0.0889 | likely_benign | 0.0877 | benign | -0.411 | Destabilizing | 0.01 | N | 0.259 | neutral | None | None | None | None | N |
| D/T | 0.1241 | likely_benign | 0.1298 | benign | -0.255 | Destabilizing | 0.241 | N | 0.4 | neutral | None | None | None | None | N |
| D/V | 0.1257 | likely_benign | 0.1318 | benign | -0.162 | Destabilizing | 0.773 | D | 0.45 | neutral | N | 0.497498602 | None | None | N |
| D/W | 0.6889 | likely_pathogenic | 0.7163 | pathogenic | -0.234 | Destabilizing | 0.981 | D | 0.524 | neutral | None | None | None | None | N |
| D/Y | 0.1792 | likely_benign | 0.1824 | benign | -0.173 | Destabilizing | 0.912 | D | 0.45 | neutral | N | 0.495030718 | 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.