Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24368 | 73327;73328;73329 | chr2:178573030;178573029;178573028 | chr2:179437757;179437756;179437755 |
| N2AB | 22727 | 68404;68405;68406 | chr2:178573030;178573029;178573028 | chr2:179437757;179437756;179437755 |
| N2A | 21800 | 65623;65624;65625 | chr2:178573030;178573029;178573028 | chr2:179437757;179437756;179437755 |
| N2B | 15303 | 46132;46133;46134 | chr2:178573030;178573029;178573028 | chr2:179437757;179437756;179437755 |
| Novex-1 | 15428 | 46507;46508;46509 | chr2:178573030;178573029;178573028 | chr2:179437757;179437756;179437755 |
| Novex-2 | 15495 | 46708;46709;46710 | chr2:178573030;178573029;178573028 | chr2:179437757;179437756;179437755 |
| 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/H | None | None | 0.999 | N | 0.72 | 0.381 | 0.425028116352 | gnomAD-4.0.0 | 6.84511E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65761E-05 |
| D/N | None | None | 0.998 | N | 0.688 | 0.306 | 0.327952845175 | gnomAD-4.0.0 | 1.36902E-06 | None | None | None | None | N | None | 5.98086E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs886042474  |
None | 0.998 | N | 0.741 | 0.43 | 0.654079243945 | gnomAD-4.0.0 | 6.84511E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99701E-07 | 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 | 0.111 | likely_benign | 0.1113 | benign | -0.364 | Destabilizing | 0.919 | D | 0.609 | neutral | N | 0.48074992 | None | None | N |
| D/C | 0.4606 | ambiguous | 0.4655 | ambiguous | -0.287 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| D/E | 0.0802 | likely_benign | 0.0845 | benign | -0.347 | Destabilizing | 0.979 | D | 0.533 | neutral | N | 0.418525238 | None | None | N |
| D/F | 0.5048 | ambiguous | 0.5055 | ambiguous | -0.115 | Destabilizing | 0.991 | D | 0.748 | deleterious | None | None | None | None | N |
| D/G | 0.0948 | likely_benign | 0.0948 | benign | -0.572 | Destabilizing | 0.979 | D | 0.641 | neutral | N | 0.44476769 | None | None | N |
| D/H | 0.233 | likely_benign | 0.2326 | benign | 0.256 | Stabilizing | 0.999 | D | 0.72 | prob.delet. | N | 0.481484096 | None | None | N |
| D/I | 0.2421 | likely_benign | 0.2428 | benign | 0.146 | Stabilizing | 0.982 | D | 0.677 | prob.neutral | None | None | None | None | N |
| D/K | 0.189 | likely_benign | 0.188 | benign | 0.097 | Stabilizing | 0.995 | D | 0.707 | prob.neutral | None | None | None | None | N |
| D/L | 0.2656 | likely_benign | 0.2601 | benign | 0.146 | Stabilizing | 0.982 | D | 0.661 | neutral | None | None | None | None | N |
| D/M | 0.363 | ambiguous | 0.3699 | ambiguous | 0.113 | Stabilizing | 0.999 | D | 0.741 | deleterious | None | None | None | None | N |
| D/N | 0.084 | likely_benign | 0.0845 | benign | -0.292 | Destabilizing | 0.998 | D | 0.688 | prob.neutral | N | 0.479997771 | None | None | N |
| D/P | 0.4298 | ambiguous | 0.4332 | ambiguous | -0.003 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | None | None | None | None | N |
| D/Q | 0.1977 | likely_benign | 0.202 | benign | -0.233 | Destabilizing | 0.998 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/R | 0.2592 | likely_benign | 0.2537 | benign | 0.445 | Stabilizing | 0.995 | D | 0.741 | deleterious | None | None | None | None | N |
| D/S | 0.0983 | likely_benign | 0.1022 | benign | -0.413 | Destabilizing | 0.995 | D | 0.658 | neutral | None | None | None | None | N |
| D/T | 0.1363 | likely_benign | 0.1402 | benign | -0.241 | Destabilizing | 0.991 | D | 0.675 | neutral | None | None | None | None | N |
| D/V | 0.1446 | likely_benign | 0.1416 | benign | -0.003 | Destabilizing | 0.142 | N | 0.601 | neutral | N | 0.50418414 | None | None | N |
| D/W | 0.7678 | likely_pathogenic | 0.7645 | pathogenic | 0.07 | Stabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| D/Y | 0.204 | likely_benign | 0.1967 | benign | 0.131 | Stabilizing | 0.998 | D | 0.741 | deleterious | N | 0.474393751 | 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.