Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31453 | 94582;94583;94584 | chr2:178547168;178547167;178547166 | chr2:179411895;179411894;179411893 |
| N2AB | 29812 | 89659;89660;89661 | chr2:178547168;178547167;178547166 | chr2:179411895;179411894;179411893 |
| N2A | 28885 | 86878;86879;86880 | chr2:178547168;178547167;178547166 | chr2:179411895;179411894;179411893 |
| N2B | 22388 | 67387;67388;67389 | chr2:178547168;178547167;178547166 | chr2:179411895;179411894;179411893 |
| Novex-1 | 22513 | 67762;67763;67764 | chr2:178547168;178547167;178547166 | chr2:179411895;179411894;179411893 |
| Novex-2 | 22580 | 67963;67964;67965 | chr2:178547168;178547167;178547166 | chr2:179411895;179411894;179411893 |
| 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/F | rs780232811  |
-0.498 | 1.0 | N | 0.649 | 0.411 | 0.652986081711 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/F | rs780232811 |
-0.498 | 1.0 | N | 0.649 | 0.411 | 0.652986081711 | gnomAD-4.0.0 | 6.84196E-07 | None | None | None | None | I | None | 0 | 2.23604E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs780232811 |
None | 0.993 | N | 0.494 | 0.215 | 0.511047945453 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 1.30907E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs780232811 |
None | 0.993 | N | 0.494 | 0.215 | 0.511047945453 | gnomAD-4.0.0 | 4.33778E-06 | None | None | None | None | I | None | 0 | 5E-05 | None | 0 | 0 | None | 0 | 0 | 3.39042E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9614 | likely_pathogenic | 0.9524 | pathogenic | -0.457 | Destabilizing | 0.999 | D | 0.582 | neutral | None | None | None | None | I |
| I/C | 0.993 | likely_pathogenic | 0.9892 | pathogenic | -0.738 | Destabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | I |
| I/D | 0.9971 | likely_pathogenic | 0.9961 | pathogenic | -0.22 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | I |
| I/E | 0.9961 | likely_pathogenic | 0.995 | pathogenic | -0.301 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| I/F | 0.8502 | likely_pathogenic | 0.813 | pathogenic | -0.592 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.466582618 | None | None | I |
| I/G | 0.9952 | likely_pathogenic | 0.9934 | pathogenic | -0.565 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | I |
| I/H | 0.9931 | likely_pathogenic | 0.9904 | pathogenic | 0.128 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | I |
| I/K | 0.9891 | likely_pathogenic | 0.9846 | pathogenic | -0.301 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| I/L | 0.3513 | ambiguous | 0.3324 | benign | -0.286 | Destabilizing | 0.993 | D | 0.479 | neutral | N | 0.423472485 | None | None | I |
| I/M | 0.5763 | likely_pathogenic | 0.5334 | ambiguous | -0.614 | Destabilizing | 1.0 | D | 0.661 | neutral | N | 0.477960331 | None | None | I |
| I/N | 0.976 | likely_pathogenic | 0.9616 | pathogenic | -0.174 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | N | 0.423528413 | None | None | I |
| I/P | 0.981 | likely_pathogenic | 0.9749 | pathogenic | -0.316 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| I/Q | 0.9917 | likely_pathogenic | 0.9881 | pathogenic | -0.336 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | I |
| I/R | 0.9775 | likely_pathogenic | 0.9717 | pathogenic | 0.149 | Stabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | I |
| I/S | 0.9693 | likely_pathogenic | 0.9548 | pathogenic | -0.56 | Destabilizing | 1.0 | D | 0.625 | neutral | N | 0.450523013 | None | None | I |
| I/T | 0.9829 | likely_pathogenic | 0.9696 | pathogenic | -0.539 | Destabilizing | 1.0 | D | 0.583 | neutral | N | 0.436246994 | None | None | I |
| I/V | 0.3315 | likely_benign | 0.2762 | benign | -0.316 | Destabilizing | 0.993 | D | 0.494 | neutral | N | 0.475458743 | None | None | I |
| I/W | 0.9914 | likely_pathogenic | 0.9904 | pathogenic | -0.613 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| I/Y | 0.9668 | likely_pathogenic | 0.9619 | pathogenic | -0.378 | Destabilizing | 1.0 | D | 0.635 | 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.