Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15197 | 45814;45815;45816 | chr2:178621129;178621128;178621127 | chr2:179485856;179485855;179485854 |
| N2AB | 13556 | 40891;40892;40893 | chr2:178621129;178621128;178621127 | chr2:179485856;179485855;179485854 |
| N2A | 12629 | 38110;38111;38112 | chr2:178621129;178621128;178621127 | chr2:179485856;179485855;179485854 |
| N2B | 6132 | 18619;18620;18621 | chr2:178621129;178621128;178621127 | chr2:179485856;179485855;179485854 |
| Novex-1 | 6257 | 18994;18995;18996 | chr2:178621129;178621128;178621127 | chr2:179485856;179485855;179485854 |
| Novex-2 | 6324 | 19195;19196;19197 | chr2:178621129;178621128;178621127 | chr2:179485856;179485855;179485854 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs748906368  |
-1.076 | 0.896 | D | 0.575 | 0.279 | 0.386558576397 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 0 |
| R/G | rs748906368 |
-1.076 | 0.896 | D | 0.575 | 0.279 | 0.386558576397 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/G | rs748906368 |
-1.076 | 0.896 | D | 0.575 | 0.279 | 0.386558576397 | gnomAD-4.0.0 | 9.92305E-06 | None | None | None | None | N | None | 0 | 6.68919E-05 | None | 0 | 0 | None | 3.1252E-05 | 0 | 8.47998E-06 | 0 | 0 |
| R/S | rs777451653 |
-0.834 | 0.251 | N | 0.299 | 0.096 | 0.148003135375 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/S | rs777451653 |
-0.834 | 0.251 | N | 0.299 | 0.096 | 0.148003135375 | gnomAD-4.0.0 | 1.59398E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4348E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5847 | likely_pathogenic | 0.6062 | pathogenic | 0.152 | Stabilizing | 0.702 | D | 0.562 | neutral | None | None | None | None | N |
| R/C | 0.401 | ambiguous | 0.3819 | ambiguous | -0.083 | Destabilizing | 0.999 | D | 0.656 | neutral | None | None | None | None | N |
| R/D | 0.8533 | likely_pathogenic | 0.8649 | pathogenic | -0.156 | Destabilizing | 0.976 | D | 0.619 | neutral | None | None | None | None | N |
| R/E | 0.4534 | ambiguous | 0.4721 | ambiguous | -0.092 | Destabilizing | 0.851 | D | 0.613 | neutral | None | None | None | None | N |
| R/F | 0.7909 | likely_pathogenic | 0.8008 | pathogenic | -0.075 | Destabilizing | 0.996 | D | 0.661 | neutral | None | None | None | None | N |
| R/G | 0.5048 | ambiguous | 0.5281 | ambiguous | -0.032 | Destabilizing | 0.896 | D | 0.575 | neutral | D | 0.559521212 | None | None | N |
| R/H | 0.1933 | likely_benign | 0.205 | benign | -0.569 | Destabilizing | 0.996 | D | 0.636 | neutral | None | None | None | None | N |
| R/I | 0.4754 | ambiguous | 0.4963 | ambiguous | 0.597 | Stabilizing | 0.984 | D | 0.662 | neutral | N | 0.433375387 | None | None | N |
| R/K | 0.1418 | likely_benign | 0.1462 | benign | 0.034 | Stabilizing | 0.011 | N | 0.234 | neutral | N | 0.421788058 | None | None | N |
| R/L | 0.475 | ambiguous | 0.4873 | ambiguous | 0.597 | Stabilizing | 0.919 | D | 0.598 | neutral | None | None | None | None | N |
| R/M | 0.4665 | ambiguous | 0.4831 | ambiguous | 0.062 | Stabilizing | 0.999 | D | 0.63 | neutral | None | None | None | None | N |
| R/N | 0.7682 | likely_pathogenic | 0.7845 | pathogenic | 0.157 | Stabilizing | 0.919 | D | 0.609 | neutral | None | None | None | None | N |
| R/P | 0.8937 | likely_pathogenic | 0.8961 | pathogenic | 0.469 | Stabilizing | 0.988 | D | 0.66 | neutral | None | None | None | None | N |
| R/Q | 0.1453 | likely_benign | 0.1606 | benign | 0.117 | Stabilizing | 0.919 | D | 0.635 | neutral | None | None | None | None | N |
| R/S | 0.6425 | likely_pathogenic | 0.6633 | pathogenic | -0.07 | Destabilizing | 0.251 | N | 0.299 | neutral | N | 0.435245123 | None | None | N |
| R/T | 0.3764 | ambiguous | 0.384 | ambiguous | 0.122 | Stabilizing | 0.811 | D | 0.565 | neutral | N | 0.418874761 | None | None | N |
| R/V | 0.5097 | ambiguous | 0.5294 | ambiguous | 0.469 | Stabilizing | 0.988 | D | 0.634 | neutral | None | None | None | None | N |
| R/W | 0.4093 | ambiguous | 0.4028 | ambiguous | -0.21 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| R/Y | 0.6766 | likely_pathogenic | 0.6854 | pathogenic | 0.21 | Stabilizing | 0.996 | D | 0.653 | neutral | None | None | 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.