Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24485 | 73678;73679;73680 | chr2:178572679;178572678;178572677 | chr2:179437406;179437405;179437404 |
| N2AB | 22844 | 68755;68756;68757 | chr2:178572679;178572678;178572677 | chr2:179437406;179437405;179437404 |
| N2A | 21917 | 65974;65975;65976 | chr2:178572679;178572678;178572677 | chr2:179437406;179437405;179437404 |
| N2B | 15420 | 46483;46484;46485 | chr2:178572679;178572678;178572677 | chr2:179437406;179437405;179437404 |
| Novex-1 | 15545 | 46858;46859;46860 | chr2:178572679;178572678;178572677 | chr2:179437406;179437405;179437404 |
| Novex-2 | 15612 | 47059;47060;47061 | chr2:178572679;178572678;178572677 | chr2:179437406;179437405;179437404 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1708656182  |
None | None | N | 0.26 | 0.105 | 0.518312163451 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| I/T | rs1708656182 |
None | None | N | 0.26 | 0.105 | 0.518312163451 | gnomAD-4.0.0 | 6.57402E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3058 | likely_benign | 0.282 | benign | -2.033 | Highly Destabilizing | 0.016 | N | 0.404 | neutral | None | None | None | None | N |
| I/C | 0.6686 | likely_pathogenic | 0.7004 | pathogenic | -1.404 | Destabilizing | 0.676 | D | 0.473 | neutral | None | None | None | None | N |
| I/D | 0.7932 | likely_pathogenic | 0.81 | pathogenic | -1.553 | Destabilizing | 0.072 | N | 0.539 | neutral | None | None | None | None | N |
| I/E | 0.6066 | likely_pathogenic | 0.6245 | pathogenic | -1.465 | Destabilizing | 0.038 | N | 0.506 | neutral | None | None | None | None | N |
| I/F | 0.2356 | likely_benign | 0.2271 | benign | -1.229 | Destabilizing | 0.171 | N | 0.469 | neutral | N | 0.481822647 | None | None | N |
| I/G | 0.7585 | likely_pathogenic | 0.7403 | pathogenic | -2.446 | Highly Destabilizing | 0.072 | N | 0.525 | neutral | None | None | None | None | N |
| I/H | 0.512 | ambiguous | 0.5471 | ambiguous | -1.63 | Destabilizing | 0.356 | N | 0.527 | neutral | None | None | None | None | N |
| I/K | 0.5326 | ambiguous | 0.5505 | ambiguous | -1.466 | Destabilizing | 0.038 | N | 0.497 | neutral | None | None | None | None | N |
| I/L | 0.1216 | likely_benign | 0.12 | benign | -0.921 | Destabilizing | None | N | 0.191 | neutral | N | 0.438378514 | None | None | N |
| I/M | 0.0945 | likely_benign | 0.0961 | benign | -0.845 | Destabilizing | 0.171 | N | 0.478 | neutral | N | 0.484593594 | None | None | N |
| I/N | 0.3442 | ambiguous | 0.3576 | ambiguous | -1.435 | Destabilizing | 0.055 | N | 0.551 | neutral | N | 0.503352713 | None | None | N |
| I/P | 0.9517 | likely_pathogenic | 0.9482 | pathogenic | -1.264 | Destabilizing | 0.356 | N | 0.567 | neutral | None | None | None | None | N |
| I/Q | 0.4473 | ambiguous | 0.4693 | ambiguous | -1.509 | Destabilizing | 0.003 | N | 0.422 | neutral | None | None | None | None | N |
| I/R | 0.4108 | ambiguous | 0.4251 | ambiguous | -0.961 | Destabilizing | None | N | 0.461 | neutral | None | None | None | None | N |
| I/S | 0.27 | likely_benign | 0.2673 | benign | -2.154 | Highly Destabilizing | 0.012 | N | 0.495 | neutral | N | 0.463063528 | None | None | N |
| I/T | 0.1163 | likely_benign | 0.1134 | benign | -1.942 | Destabilizing | None | N | 0.26 | neutral | N | 0.437047576 | None | None | N |
| I/V | 0.0777 | likely_benign | 0.0657 | benign | -1.264 | Destabilizing | None | N | 0.178 | neutral | N | 0.380119645 | None | None | N |
| I/W | 0.7932 | likely_pathogenic | 0.8295 | pathogenic | -1.377 | Destabilizing | 0.864 | D | 0.562 | neutral | None | None | None | None | N |
| I/Y | 0.5643 | likely_pathogenic | 0.6053 | pathogenic | -1.142 | Destabilizing | 0.356 | N | 0.516 | 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.