Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2717 | 8374;8375;8376 | chr2:178770643;178770642;178770641 | chr2:179635370;179635369;179635368 |
| N2AB | 2717 | 8374;8375;8376 | chr2:178770643;178770642;178770641 | chr2:179635370;179635369;179635368 |
| N2A | 2717 | 8374;8375;8376 | chr2:178770643;178770642;178770641 | chr2:179635370;179635369;179635368 |
| N2B | 2671 | 8236;8237;8238 | chr2:178770643;178770642;178770641 | chr2:179635370;179635369;179635368 |
| Novex-1 | 2671 | 8236;8237;8238 | chr2:178770643;178770642;178770641 | chr2:179635370;179635369;179635368 |
| Novex-2 | 2671 | 8236;8237;8238 | chr2:178770643;178770642;178770641 | chr2:179635370;179635369;179635368 |
| Novex-3 | 2717 | 8374;8375;8376 | chr2:178770643;178770642;178770641 | chr2:179635370;179635369;179635368 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs1478991790  |
None | 0.999 | D | 0.548 | 0.475 | 0.352693368174 | gnomAD-4.0.0 | 1.59148E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85657E-06 | 0 | 0 |
| T/K | rs781565875 |
-0.216 | 1.0 | D | 0.693 | 0.486 | 0.566666267248 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.81E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2092 | likely_benign | 0.1917 | benign | -0.175 | Destabilizing | 0.999 | D | 0.548 | neutral | D | 0.592122466 | None | None | I |
| T/C | 0.8026 | likely_pathogenic | 0.793 | pathogenic | -0.633 | Destabilizing | 1.0 | D | 0.597 | neutral | None | None | None | None | I |
| T/D | 0.8188 | likely_pathogenic | 0.7866 | pathogenic | -0.247 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| T/E | 0.6804 | likely_pathogenic | 0.6205 | pathogenic | -0.334 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| T/F | 0.5929 | likely_pathogenic | 0.5803 | pathogenic | -0.885 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| T/G | 0.6953 | likely_pathogenic | 0.6752 | pathogenic | -0.203 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| T/H | 0.5415 | ambiguous | 0.5011 | ambiguous | -0.272 | Destabilizing | 1.0 | D | 0.634 | neutral | None | None | None | None | I |
| T/I | 0.4109 | ambiguous | 0.3949 | ambiguous | -0.218 | Destabilizing | 1.0 | D | 0.669 | neutral | D | 0.619840956 | None | None | I |
| T/K | 0.5258 | ambiguous | 0.47 | ambiguous | -0.452 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | D | 0.53092251 | None | None | I |
| T/L | 0.2452 | likely_benign | 0.2388 | benign | -0.218 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | I |
| T/M | 0.1411 | likely_benign | 0.1386 | benign | -0.402 | Destabilizing | 1.0 | D | 0.608 | neutral | None | None | None | None | I |
| T/N | 0.326 | likely_benign | 0.3056 | benign | -0.348 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| T/P | 0.524 | ambiguous | 0.4839 | ambiguous | -0.183 | Destabilizing | 1.0 | D | 0.643 | neutral | D | 0.660008444 | None | None | I |
| T/Q | 0.4618 | ambiguous | 0.4276 | ambiguous | -0.505 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| T/R | 0.4466 | ambiguous | 0.388 | ambiguous | -0.156 | Destabilizing | 1.0 | D | 0.648 | neutral | D | 0.577588989 | None | None | I |
| T/S | 0.2688 | likely_benign | 0.2577 | benign | -0.466 | Destabilizing | 0.999 | D | 0.567 | neutral | N | 0.500115887 | None | None | I |
| T/V | 0.2928 | likely_benign | 0.287 | benign | -0.183 | Destabilizing | 0.999 | D | 0.625 | neutral | None | None | None | None | I |
| T/W | 0.8713 | likely_pathogenic | 0.8418 | pathogenic | -1.019 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | I |
| T/Y | 0.6677 | likely_pathogenic | 0.6408 | pathogenic | -0.694 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | 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.