Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2909 | 8950;8951;8952 | chr2:178769856;178769855;178769854 | chr2:179634583;179634582;179634581 |
| N2AB | 2909 | 8950;8951;8952 | chr2:178769856;178769855;178769854 | chr2:179634583;179634582;179634581 |
| N2A | 2909 | 8950;8951;8952 | chr2:178769856;178769855;178769854 | chr2:179634583;179634582;179634581 |
| N2B | 2863 | 8812;8813;8814 | chr2:178769856;178769855;178769854 | chr2:179634583;179634582;179634581 |
| Novex-1 | 2863 | 8812;8813;8814 | chr2:178769856;178769855;178769854 | chr2:179634583;179634582;179634581 |
| Novex-2 | 2863 | 8812;8813;8814 | chr2:178769856;178769855;178769854 | chr2:179634583;179634582;179634581 |
| Novex-3 | 2909 | 8950;8951;8952 | chr2:178769856;178769855;178769854 | chr2:179634583;179634582;179634581 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs1300254374  |
0.143 | 0.999 | N | 0.633 | 0.4 | 0.26547132957 | gnomAD-2.1.1 | 1.77E-05 | None | None | None | None | I | None | 0 | 8.47E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.55E-05 | 0 |
| N/S | rs1300254374 |
0.143 | 0.999 | N | 0.633 | 0.4 | 0.26547132957 | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | I | None | 0 | 4.58235E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| N/S | rs1300254374 |
0.143 | 0.999 | N | 0.633 | 0.4 | 0.26547132957 | gnomAD-4.0.0 | 1.487E-05 | None | None | None | None | I | None | 1.33472E-05 | 1.83339E-04 | None | 0 | 0 | None | 0 | 0 | 1.01695E-05 | 0 | 0 |
| N/Y | None | None | 1.0 | D | 0.588 | 0.626 | 0.697725006634 | gnomAD-4.0.0 | 7.52473E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.89225E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.7621 | likely_pathogenic | 0.688 | pathogenic | -0.034 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | I |
| N/C | 0.8107 | likely_pathogenic | 0.7394 | pathogenic | 0.071 | Stabilizing | 1.0 | D | 0.63 | neutral | None | None | None | None | I |
| N/D | 0.6279 | likely_pathogenic | 0.512 | ambiguous | 0.183 | Stabilizing | 0.999 | D | 0.689 | prob.neutral | N | 0.464822867 | None | None | I |
| N/E | 0.9368 | likely_pathogenic | 0.9036 | pathogenic | 0.129 | Stabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | I |
| N/F | 0.9424 | likely_pathogenic | 0.9155 | pathogenic | -0.661 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | I |
| N/G | 0.7478 | likely_pathogenic | 0.6925 | pathogenic | -0.126 | Destabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | I |
| N/H | 0.4289 | ambiguous | 0.348 | ambiguous | -0.097 | Destabilizing | 1.0 | D | 0.674 | neutral | D | 0.613116445 | None | None | I |
| N/I | 0.8573 | likely_pathogenic | 0.7854 | pathogenic | 0.107 | Stabilizing | 1.0 | D | 0.645 | neutral | D | 0.589677384 | None | None | I |
| N/K | 0.9477 | likely_pathogenic | 0.9189 | pathogenic | 0.141 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | N | 0.506768278 | None | None | I |
| N/L | 0.6831 | likely_pathogenic | 0.6074 | pathogenic | 0.107 | Stabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | I |
| N/M | 0.86 | likely_pathogenic | 0.8135 | pathogenic | 0.008 | Stabilizing | 1.0 | D | 0.579 | neutral | None | None | None | None | I |
| N/P | 0.8926 | likely_pathogenic | 0.8586 | pathogenic | 0.083 | Stabilizing | 1.0 | D | 0.6 | neutral | None | None | None | None | I |
| N/Q | 0.8667 | likely_pathogenic | 0.8294 | pathogenic | -0.228 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| N/R | 0.9045 | likely_pathogenic | 0.8642 | pathogenic | 0.213 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| N/S | 0.2039 | likely_benign | 0.1666 | benign | -0.04 | Destabilizing | 0.999 | D | 0.633 | neutral | N | 0.507863302 | None | None | I |
| N/T | 0.6204 | likely_pathogenic | 0.5269 | ambiguous | 0.021 | Stabilizing | 0.999 | D | 0.684 | prob.neutral | N | 0.508820132 | None | None | I |
| N/V | 0.8421 | likely_pathogenic | 0.7735 | pathogenic | 0.083 | Stabilizing | 1.0 | D | 0.622 | neutral | None | None | None | None | I |
| N/W | 0.9757 | likely_pathogenic | 0.9687 | pathogenic | -0.821 | Destabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | I |
| N/Y | 0.7049 | likely_pathogenic | 0.6138 | pathogenic | -0.472 | Destabilizing | 1.0 | D | 0.588 | neutral | D | 0.590708744 | 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.