Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17177 | 51754;51755;51756 | chr2:178609894;178609893;178609892 | chr2:179474621;179474620;179474619 |
| N2AB | 15536 | 46831;46832;46833 | chr2:178609894;178609893;178609892 | chr2:179474621;179474620;179474619 |
| N2A | 14609 | 44050;44051;44052 | chr2:178609894;178609893;178609892 | chr2:179474621;179474620;179474619 |
| N2B | 8112 | 24559;24560;24561 | chr2:178609894;178609893;178609892 | chr2:179474621;179474620;179474619 |
| Novex-1 | 8237 | 24934;24935;24936 | chr2:178609894;178609893;178609892 | chr2:179474621;179474620;179474619 |
| Novex-2 | 8304 | 25135;25136;25137 | chr2:178609894;178609893;178609892 | chr2:179474621;179474620;179474619 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs745512911  |
-0.215 | 0.801 | N | 0.665 | 0.231 | 0.197625483188 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| S/N | rs745512911 |
-0.215 | 0.801 | N | 0.665 | 0.231 | 0.197625483188 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.78927E-04 |
| S/N | rs745512911 |
-0.215 | 0.801 | N | 0.665 | 0.231 | 0.197625483188 | gnomAD-4.0.0 | 1.17801E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.52638E-05 | 0 | 1.60251E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1475 | likely_benign | 0.1516 | benign | -0.435 | Destabilizing | 0.029 | N | 0.319 | neutral | None | None | None | None | I |
| S/C | 0.0944 | likely_benign | 0.0857 | benign | -0.201 | Destabilizing | 0.012 | N | 0.392 | neutral | N | 0.502976206 | None | None | I |
| S/D | 0.9176 | likely_pathogenic | 0.8846 | pathogenic | -0.198 | Destabilizing | 0.842 | D | 0.621 | neutral | None | None | None | None | I |
| S/E | 0.9363 | likely_pathogenic | 0.9124 | pathogenic | -0.284 | Destabilizing | 0.842 | D | 0.611 | neutral | None | None | None | None | I |
| S/F | 0.7422 | likely_pathogenic | 0.7004 | pathogenic | -0.997 | Destabilizing | 0.974 | D | 0.695 | prob.neutral | None | None | None | None | I |
| S/G | 0.2873 | likely_benign | 0.2834 | benign | -0.567 | Destabilizing | 0.625 | D | 0.495 | neutral | N | 0.509933889 | None | None | I |
| S/H | 0.8403 | likely_pathogenic | 0.7831 | pathogenic | -1.141 | Destabilizing | 0.998 | D | 0.627 | neutral | None | None | None | None | I |
| S/I | 0.7827 | likely_pathogenic | 0.7598 | pathogenic | -0.211 | Destabilizing | 0.801 | D | 0.712 | prob.delet. | N | 0.501882983 | None | None | I |
| S/K | 0.9898 | likely_pathogenic | 0.9846 | pathogenic | -0.511 | Destabilizing | 0.842 | D | 0.571 | neutral | None | None | None | None | I |
| S/L | 0.4449 | ambiguous | 0.4118 | ambiguous | -0.211 | Destabilizing | 0.728 | D | 0.623 | neutral | None | None | None | None | I |
| S/M | 0.5409 | ambiguous | 0.5235 | ambiguous | 0.245 | Stabilizing | 0.991 | D | 0.628 | neutral | None | None | None | None | I |
| S/N | 0.52 | ambiguous | 0.4725 | ambiguous | -0.249 | Destabilizing | 0.801 | D | 0.665 | neutral | N | 0.485424569 | None | None | I |
| S/P | 0.9942 | likely_pathogenic | 0.9926 | pathogenic | -0.257 | Destabilizing | 0.974 | D | 0.661 | neutral | None | None | None | None | I |
| S/Q | 0.8877 | likely_pathogenic | 0.8618 | pathogenic | -0.571 | Destabilizing | 0.974 | D | 0.607 | neutral | None | None | None | None | I |
| S/R | 0.9775 | likely_pathogenic | 0.9665 | pathogenic | -0.26 | Destabilizing | 0.934 | D | 0.657 | neutral | N | 0.499855067 | None | None | I |
| S/T | 0.2809 | likely_benign | 0.2584 | benign | -0.334 | Destabilizing | 0.051 | N | 0.355 | neutral | N | 0.474637695 | None | None | I |
| S/V | 0.6531 | likely_pathogenic | 0.6247 | pathogenic | -0.257 | Destabilizing | 0.728 | D | 0.619 | neutral | None | None | None | None | I |
| S/W | 0.8726 | likely_pathogenic | 0.8104 | pathogenic | -0.976 | Destabilizing | 0.998 | D | 0.723 | prob.delet. | None | None | None | None | I |
| S/Y | 0.7104 | likely_pathogenic | 0.6324 | pathogenic | -0.702 | Destabilizing | 0.991 | D | 0.693 | prob.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.