Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17086 | 51481;51482;51483 | chr2:178610270;178610269;178610268 | chr2:179474997;179474996;179474995 |
| N2AB | 15445 | 46558;46559;46560 | chr2:178610270;178610269;178610268 | chr2:179474997;179474996;179474995 |
| N2A | 14518 | 43777;43778;43779 | chr2:178610270;178610269;178610268 | chr2:179474997;179474996;179474995 |
| N2B | 8021 | 24286;24287;24288 | chr2:178610270;178610269;178610268 | chr2:179474997;179474996;179474995 |
| Novex-1 | 8146 | 24661;24662;24663 | chr2:178610270;178610269;178610268 | chr2:179474997;179474996;179474995 |
| Novex-2 | 8213 | 24862;24863;24864 | chr2:178610270;178610269;178610268 | chr2:179474997;179474996;179474995 |
| 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/C | rs751267287  |
-2.236 | 1.0 | N | 0.845 | 0.427 | None | gnomAD-2.1.1 | 4.03E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 1.11769E-04 | None | 9.81E-05 | None | 0 | 3.56E-05 | 0 |
| R/C | rs751267287 |
-2.236 | 1.0 | N | 0.845 | 0.427 | None | gnomAD-4.0.0 | 2.80657E-05 | None | None | None | None | N | None | 2.99312E-05 | 2.23694E-05 | None | 0 | 3.02801E-04 | None | 0 | 0 | 2.06963E-05 | 4.63886E-05 | 0 |
| R/H | rs72632860 |
-1.941 | 1.0 | N | 0.88 | 0.372 | None | gnomAD-2.1.1 | 5.36E-05 | None | None | None | None | N | None | 1.24049E-04 | 0 | None | 3.87372E-04 | 1.54575E-04 | None | 6.54E-05 | None | 0 | 2.35E-05 | 0 |
| R/H | rs72632860 |
-1.941 | 1.0 | N | 0.88 | 0.372 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 1.94704E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs72632860 |
-1.941 | 1.0 | N | 0.88 | 0.372 | None | gnomAD-4.0.0 | 4.21622E-05 | None | None | None | None | N | None | 9.35429E-05 | 0 | None | 3.04342E-04 | 1.78723E-04 | None | 1.56226E-05 | 0 | 2.71359E-05 | 8.78522E-05 | 4.80769E-05 |
| R/L | None | None | 1.0 | N | 0.833 | 0.443 | 0.437527004654 | gnomAD-4.0.0 | 2.05359E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87273E-05 | 0 | 0 | 2.31943E-05 | 0 |
| R/P | rs72632860 |
None | 1.0 | N | 0.862 | 0.499 | 0.456275507713 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/P | rs72632860 |
None | 1.0 | N | 0.862 | 0.499 | 0.456275507713 | gnomAD-4.0.0 | 6.58059E-06 | None | None | None | None | N | None | 2.41429E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | None | None | 1.0 | N | 0.825 | 0.471 | 0.391313282164 | gnomAD-4.0.0 | 3.42265E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49919E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9851 | likely_pathogenic | 0.9803 | pathogenic | -2.207 | Highly Destabilizing | 0.999 | D | 0.736 | prob.delet. | None | None | None | None | N |
| R/C | 0.8465 | likely_pathogenic | 0.7203 | pathogenic | -2.226 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | N | 0.521460392 | None | None | N |
| R/D | 0.9978 | likely_pathogenic | 0.9975 | pathogenic | -1.946 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| R/E | 0.9739 | likely_pathogenic | 0.968 | pathogenic | -1.69 | Destabilizing | 0.999 | D | 0.768 | deleterious | None | None | None | None | N |
| R/F | 0.987 | likely_pathogenic | 0.984 | pathogenic | -1.21 | Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| R/G | 0.9735 | likely_pathogenic | 0.9637 | pathogenic | -2.572 | Highly Destabilizing | 1.0 | D | 0.833 | deleterious | N | 0.466013187 | None | None | N |
| R/H | 0.782 | likely_pathogenic | 0.7514 | pathogenic | -1.706 | Destabilizing | 1.0 | D | 0.88 | deleterious | N | 0.470532637 | None | None | N |
| R/I | 0.9589 | likely_pathogenic | 0.9473 | pathogenic | -1.114 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| R/K | 0.4587 | ambiguous | 0.4344 | ambiguous | -1.354 | Destabilizing | 0.998 | D | 0.668 | neutral | None | None | None | None | N |
| R/L | 0.9194 | likely_pathogenic | 0.8851 | pathogenic | -1.114 | Destabilizing | 1.0 | D | 0.833 | deleterious | N | 0.494447149 | None | None | N |
| R/M | 0.9511 | likely_pathogenic | 0.9299 | pathogenic | -1.549 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| R/N | 0.9946 | likely_pathogenic | 0.9943 | pathogenic | -2.162 | Highly Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| R/P | 0.9989 | likely_pathogenic | 0.9987 | pathogenic | -1.472 | Destabilizing | 1.0 | D | 0.862 | deleterious | N | 0.495727237 | None | None | N |
| R/Q | 0.7091 | likely_pathogenic | 0.646 | pathogenic | -1.912 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| R/S | 0.9936 | likely_pathogenic | 0.9919 | pathogenic | -2.905 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | N | 0.466987465 | None | None | N |
| R/T | 0.9856 | likely_pathogenic | 0.9816 | pathogenic | -2.419 | Highly Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| R/V | 0.9661 | likely_pathogenic | 0.9556 | pathogenic | -1.472 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| R/W | 0.9062 | likely_pathogenic | 0.8748 | pathogenic | -0.714 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| R/Y | 0.952 | likely_pathogenic | 0.9426 | pathogenic | -0.693 | Destabilizing | 1.0 | D | 0.872 | 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.