Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2986 | 9181;9182;9183 | chr2:178768880;178768879;178768878 | chr2:179633607;179633606;179633605 |
| N2AB | 2986 | 9181;9182;9183 | chr2:178768880;178768879;178768878 | chr2:179633607;179633606;179633605 |
| N2A | 2986 | 9181;9182;9183 | chr2:178768880;178768879;178768878 | chr2:179633607;179633606;179633605 |
| N2B | 2940 | 9043;9044;9045 | chr2:178768880;178768879;178768878 | chr2:179633607;179633606;179633605 |
| Novex-1 | 2940 | 9043;9044;9045 | chr2:178768880;178768879;178768878 | chr2:179633607;179633606;179633605 |
| Novex-2 | 2940 | 9043;9044;9045 | chr2:178768880;178768879;178768878 | chr2:179633607;179633606;179633605 |
| Novex-3 | 2986 | 9181;9182;9183 | chr2:178768880;178768879;178768878 | chr2:179633607;179633606;179633605 |
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/T | rs561206261  |
-2.726 | 0.645 | N | 0.741 | 0.281 | 0.476832112026 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs561206261 |
-2.726 | 0.645 | N | 0.741 | 0.281 | 0.476832112026 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs561206261 |
-2.726 | 0.645 | N | 0.741 | 0.281 | 0.476832112026 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/T | rs561206261 |
-2.726 | 0.645 | N | 0.741 | 0.281 | 0.476832112026 | gnomAD-4.0.0 | 3.09773E-06 | None | None | None | None | N | None | 0 | 1.66622E-05 | None | 0 | 0 | None | 0 | 0 | 3.38985E-06 | 0 | 0 |
| I/V | None | None | 0.002 | N | 0.224 | 0.081 | 0.209622950755 | gnomAD-4.0.0 | 1.59074E-06 | None | None | None | None | N | None | 0 | 2.28676E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.8636 | likely_pathogenic | 0.8661 | pathogenic | -2.408 | Highly Destabilizing | 0.547 | D | 0.63 | neutral | None | None | None | None | N |
| I/C | 0.9625 | likely_pathogenic | 0.9735 | pathogenic | -1.872 | Destabilizing | 0.985 | D | 0.742 | deleterious | None | None | None | None | N |
| I/D | 0.9987 | likely_pathogenic | 0.9987 | pathogenic | -2.108 | Highly Destabilizing | 0.945 | D | 0.797 | deleterious | None | None | None | None | N |
| I/E | 0.9948 | likely_pathogenic | 0.9949 | pathogenic | -1.926 | Destabilizing | 0.945 | D | 0.81 | deleterious | None | None | None | None | N |
| I/F | 0.8412 | likely_pathogenic | 0.8692 | pathogenic | -1.498 | Destabilizing | 0.864 | D | 0.729 | prob.delet. | N | 0.455809173 | None | None | N |
| I/G | 0.9945 | likely_pathogenic | 0.9949 | pathogenic | -2.929 | Highly Destabilizing | 0.945 | D | 0.81 | deleterious | None | None | None | None | N |
| I/H | 0.995 | likely_pathogenic | 0.9961 | pathogenic | -2.202 | Highly Destabilizing | 0.995 | D | 0.786 | deleterious | None | None | None | None | N |
| I/K | 0.9874 | likely_pathogenic | 0.9904 | pathogenic | -1.844 | Destabilizing | 0.945 | D | 0.807 | deleterious | None | None | None | None | N |
| I/L | 0.491 | ambiguous | 0.5063 | ambiguous | -0.938 | Destabilizing | 0.141 | N | 0.373 | neutral | N | 0.442419577 | None | None | N |
| I/M | 0.4789 | ambiguous | 0.5192 | ambiguous | -0.895 | Destabilizing | 0.864 | D | 0.7 | prob.neutral | N | 0.440179228 | None | None | N |
| I/N | 0.9848 | likely_pathogenic | 0.9865 | pathogenic | -2.043 | Highly Destabilizing | 0.975 | D | 0.811 | deleterious | N | 0.44118524 | None | None | N |
| I/P | 0.9976 | likely_pathogenic | 0.9977 | pathogenic | -1.404 | Destabilizing | 0.981 | D | 0.805 | deleterious | None | None | None | None | N |
| I/Q | 0.99 | likely_pathogenic | 0.9911 | pathogenic | -1.958 | Destabilizing | 0.981 | D | 0.815 | deleterious | None | None | None | None | N |
| I/R | 0.9793 | likely_pathogenic | 0.9825 | pathogenic | -1.488 | Destabilizing | 0.945 | D | 0.813 | deleterious | None | None | None | None | N |
| I/S | 0.9668 | likely_pathogenic | 0.9685 | pathogenic | -2.83 | Highly Destabilizing | 0.864 | D | 0.772 | deleterious | N | 0.440918186 | None | None | N |
| I/T | 0.9174 | likely_pathogenic | 0.9327 | pathogenic | -2.488 | Highly Destabilizing | 0.645 | D | 0.741 | deleterious | N | 0.454109368 | None | None | N |
| I/V | 0.1035 | likely_benign | 0.1117 | benign | -1.404 | Destabilizing | 0.002 | N | 0.224 | neutral | N | 0.394881291 | None | None | N |
| I/W | 0.997 | likely_pathogenic | 0.9981 | pathogenic | -1.732 | Destabilizing | 0.995 | D | 0.767 | deleterious | None | None | None | None | N |
| I/Y | 0.9833 | likely_pathogenic | 0.9881 | pathogenic | -1.47 | Destabilizing | 0.945 | D | 0.763 | deleterious | 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.