Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25902 | 77929;77930;77931 | chr2:178568428;178568427;178568426 | chr2:179433155;179433154;179433153 |
| N2AB | 24261 | 73006;73007;73008 | chr2:178568428;178568427;178568426 | chr2:179433155;179433154;179433153 |
| N2A | 23334 | 70225;70226;70227 | chr2:178568428;178568427;178568426 | chr2:179433155;179433154;179433153 |
| N2B | 16837 | 50734;50735;50736 | chr2:178568428;178568427;178568426 | chr2:179433155;179433154;179433153 |
| Novex-1 | 16962 | 51109;51110;51111 | chr2:178568428;178568427;178568426 | chr2:179433155;179433154;179433153 |
| Novex-2 | 17029 | 51310;51311;51312 | chr2:178568428;178568427;178568426 | chr2:179433155;179433154;179433153 |
| 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 | 0.002 | N | 0.171 | 0.055 | 0.0666544352282 | gnomAD-4.0.0 | 2.05335E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69889E-06 | 0 | 0 |
| D/N | None | None | 0.334 | N | 0.487 | 0.221 | 0.27855597813 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 1.94099E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | None | None | 0.638 | N | 0.653 | 0.402 | 0.477685322099 | gnomAD-4.0.0 | 1.59245E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85981E-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 | 0.1163 | likely_benign | 0.1421 | benign | -0.454 | Destabilizing | 0.201 | N | 0.477 | neutral | N | 0.477133612 | None | None | N |
| D/C | 0.4769 | ambiguous | 0.5575 | ambiguous | 0.06 | Stabilizing | 0.982 | D | 0.639 | neutral | None | None | None | None | N |
| D/E | 0.0731 | likely_benign | 0.0838 | benign | -0.352 | Destabilizing | 0.002 | N | 0.171 | neutral | N | 0.382087222 | None | None | N |
| D/F | 0.4737 | ambiguous | 0.5983 | pathogenic | -0.41 | Destabilizing | 0.935 | D | 0.655 | neutral | None | None | None | None | N |
| D/G | 0.1713 | likely_benign | 0.2046 | benign | -0.69 | Destabilizing | 0.334 | N | 0.496 | neutral | N | 0.491294987 | None | None | N |
| D/H | 0.2498 | likely_benign | 0.304 | benign | -0.547 | Destabilizing | 0.931 | D | 0.553 | neutral | N | 0.471434918 | None | None | N |
| D/I | 0.2589 | likely_benign | 0.3621 | ambiguous | 0.133 | Stabilizing | 0.826 | D | 0.674 | neutral | None | None | None | None | N |
| D/K | 0.3091 | likely_benign | 0.3671 | ambiguous | 0.172 | Stabilizing | 0.25 | N | 0.465 | neutral | None | None | None | None | N |
| D/L | 0.2987 | likely_benign | 0.3637 | ambiguous | 0.133 | Stabilizing | 0.7 | D | 0.66 | neutral | None | None | None | None | N |
| D/M | 0.384 | ambiguous | 0.4747 | ambiguous | 0.489 | Stabilizing | 0.982 | D | 0.629 | neutral | None | None | None | None | N |
| D/N | 0.0918 | likely_benign | 0.1038 | benign | -0.146 | Destabilizing | 0.334 | N | 0.487 | neutral | N | 0.464127029 | None | None | N |
| D/P | 0.9376 | likely_pathogenic | 0.947 | pathogenic | -0.04 | Destabilizing | 0.826 | D | 0.548 | neutral | None | None | None | None | N |
| D/Q | 0.2338 | likely_benign | 0.2756 | benign | -0.095 | Destabilizing | 0.539 | D | 0.474 | neutral | None | None | None | None | N |
| D/R | 0.3765 | ambiguous | 0.4469 | ambiguous | 0.221 | Stabilizing | 0.539 | D | 0.599 | neutral | None | None | None | None | N |
| D/S | 0.097 | likely_benign | 0.1154 | benign | -0.288 | Destabilizing | 0.25 | N | 0.42 | neutral | None | None | None | None | N |
| D/T | 0.146 | likely_benign | 0.1864 | benign | -0.099 | Destabilizing | 0.7 | D | 0.497 | neutral | None | None | None | None | N |
| D/V | 0.1559 | likely_benign | 0.2115 | benign | -0.04 | Destabilizing | 0.638 | D | 0.653 | neutral | N | 0.474775826 | None | None | N |
| D/W | 0.8551 | likely_pathogenic | 0.9038 | pathogenic | -0.27 | Destabilizing | 0.982 | D | 0.636 | neutral | None | None | None | None | N |
| D/Y | 0.2224 | likely_benign | 0.2946 | benign | -0.176 | Destabilizing | 0.916 | D | 0.656 | neutral | N | 0.482791223 | 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.