Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3897 | 11914;11915;11916 | chr2:178741544;178741543;178741542 | chr2:179606271;179606270;179606269 |
| N2AB | 3580 | 10963;10964;10965 | chr2:178741544;178741543;178741542 | chr2:179606271;179606270;179606269 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3534 | 10825;10826;10827 | chr2:178741544;178741543;178741542 | chr2:179606271;179606270;179606269 |
| Novex-1 | 3659 | 11200;11201;11202 | chr2:178741544;178741543;178741542 | chr2:179606271;179606270;179606269 |
| Novex-2 | 3726 | 11401;11402;11403 | chr2:178741544;178741543;178741542 | chr2:179606271;179606270;179606269 |
| 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/E | None | None | None | N | 0.067 | 0.076 | None | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25001E-06 | 0 | 0 |
| D/N | None | None | 0.014 | N | 0.229 | 0.132 | None | gnomAD-4.0.0 | 7.52618E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.09497E-06 | 0 | 3.3129E-05 |
| D/V | rs2082481128  |
None | None | N | 0.106 | 0.187 | None | gnomAD-4.0.0 | 4.78933E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.76411E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs1300532206 |
0.098 | 0.065 | N | 0.233 | 0.137 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 1.17924E-03 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/Y | rs1300532206 |
0.098 | 0.065 | N | 0.233 | 0.137 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs1300532206 |
0.098 | 0.065 | N | 0.233 | 0.137 | None | gnomAD-4.0.0 | 8.67564E-06 | None | None | None | None | I | None | 0 | 1.66744E-05 | None | 0 | 0 | None | 0 | 0 | 1.0171E-05 | 0 | 1.60102E-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 | 0.1393 | likely_benign | 0.1135 | benign | -0.185 | Destabilizing | 0.001 | N | 0.201 | neutral | N | 0.446996117 | None | None | I |
| D/C | 0.4686 | ambiguous | 0.4259 | ambiguous | -0.135 | Destabilizing | 0.497 | N | 0.185 | neutral | None | None | None | None | I |
| D/E | 0.1317 | likely_benign | 0.1066 | benign | -0.281 | Destabilizing | None | N | 0.067 | neutral | N | 0.406613965 | None | None | I |
| D/F | 0.5178 | ambiguous | 0.4411 | ambiguous | -0.082 | Destabilizing | 0.044 | N | 0.283 | neutral | None | None | None | None | I |
| D/G | 0.1397 | likely_benign | 0.1209 | benign | -0.349 | Destabilizing | 0.014 | N | 0.258 | neutral | N | 0.465070562 | None | None | I |
| D/H | 0.2056 | likely_benign | 0.1756 | benign | 0.383 | Stabilizing | 0.196 | N | 0.199 | neutral | N | 0.492659572 | None | None | I |
| D/I | 0.228 | likely_benign | 0.1807 | benign | 0.195 | Stabilizing | None | N | 0.11 | neutral | None | None | None | None | I |
| D/K | 0.2087 | likely_benign | 0.1598 | benign | 0.382 | Stabilizing | 0.004 | N | 0.216 | neutral | None | None | None | None | I |
| D/L | 0.3081 | likely_benign | 0.2523 | benign | 0.195 | Stabilizing | 0.002 | N | 0.213 | neutral | None | None | None | None | I |
| D/M | 0.5368 | ambiguous | 0.4539 | ambiguous | 0.117 | Stabilizing | 0.138 | N | 0.23 | neutral | None | None | None | None | I |
| D/N | 0.0999 | likely_benign | 0.087 | benign | 0.012 | Stabilizing | 0.014 | N | 0.229 | neutral | N | 0.477922482 | None | None | I |
| D/P | 0.5362 | ambiguous | 0.4853 | ambiguous | 0.089 | Stabilizing | 0.085 | N | 0.309 | neutral | None | None | None | None | I |
| D/Q | 0.2529 | likely_benign | 0.2043 | benign | 0.052 | Stabilizing | 0.009 | N | 0.211 | neutral | None | None | None | None | I |
| D/R | 0.2091 | likely_benign | 0.1767 | benign | 0.644 | Stabilizing | None | N | 0.081 | neutral | None | None | None | None | I |
| D/S | 0.1192 | likely_benign | 0.101 | benign | -0.075 | Destabilizing | 0.009 | N | 0.175 | neutral | None | None | None | None | I |
| D/T | 0.1962 | likely_benign | 0.1526 | benign | 0.066 | Stabilizing | 0.018 | N | 0.255 | neutral | None | None | None | None | I |
| D/V | 0.1494 | likely_benign | 0.122 | benign | 0.089 | Stabilizing | None | N | 0.106 | neutral | N | 0.473877338 | None | None | I |
| D/W | 0.7966 | likely_pathogenic | 0.7653 | pathogenic | 0.05 | Stabilizing | 0.788 | D | 0.183 | neutral | None | None | None | None | I |
| D/Y | 0.1609 | likely_benign | 0.1433 | benign | 0.165 | Stabilizing | 0.065 | N | 0.233 | neutral | N | 0.500578378 | 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.