Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22095 | 66508;66509;66510 | chr2:178582086;178582085;178582084 | chr2:179446813;179446812;179446811 |
| N2AB | 20454 | 61585;61586;61587 | chr2:178582086;178582085;178582084 | chr2:179446813;179446812;179446811 |
| N2A | 19527 | 58804;58805;58806 | chr2:178582086;178582085;178582084 | chr2:179446813;179446812;179446811 |
| N2B | 13030 | 39313;39314;39315 | chr2:178582086;178582085;178582084 | chr2:179446813;179446812;179446811 |
| Novex-1 | 13155 | 39688;39689;39690 | chr2:178582086;178582085;178582084 | chr2:179446813;179446812;179446811 |
| Novex-2 | 13222 | 39889;39890;39891 | chr2:178582086;178582085;178582084 | chr2:179446813;179446812;179446811 |
| 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/Q | rs745677076  |
-1.237 | 0.994 | N | 0.544 | 0.338 | 0.267299060538 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 1.1162E-04 | None | 3.27E-05 | None | 0 | 2.67E-05 | 0 |
| R/Q | rs745677076 |
-1.237 | 0.994 | N | 0.544 | 0.338 | 0.267299060538 | gnomAD-4.0.0 | 6.16E-06 | None | None | None | None | N | None | 5.98122E-05 | 0 | None | 0 | 2.52105E-05 | None | 0 | 0 | 3.59865E-06 | 1.15953E-05 | 1.65722E-05 |
| R/W | rs571093313 |
-0.879 | 1.0 | N | 0.721 | 0.46 | 0.443285836454 | gnomAD-2.1.1 | 6.86E-05 | None | None | None | None | N | None | 0 | 3.18896E-04 | None | 0 | 2.79205E-04 | None | 0 | None | 0 | 8.92E-06 | 0 |
| R/W | rs571093313 |
-0.879 | 1.0 | N | 0.721 | 0.46 | 0.443285836454 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 6.57E-05 | 0 | 0 | 5.83885E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/W | rs571093313 |
-0.879 | 1.0 | N | 0.721 | 0.46 | 0.443285836454 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/W | rs571093313 |
-0.879 | 1.0 | N | 0.721 | 0.46 | 0.443285836454 | gnomAD-4.0.0 | 2.54191E-05 | None | None | None | None | N | None | 0 | 2.50183E-04 | None | 0 | 1.33929E-04 | None | 0 | 1.98282E-03 | 5.08713E-06 | 0 | 3.20246E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.987 | likely_pathogenic | 0.9813 | pathogenic | -1.957 | Destabilizing | 0.845 | D | 0.544 | neutral | None | None | None | None | N |
| R/C | 0.7107 | likely_pathogenic | 0.6831 | pathogenic | -1.948 | Destabilizing | 0.999 | D | 0.767 | deleterious | None | None | None | None | N |
| R/D | 0.9976 | likely_pathogenic | 0.9969 | pathogenic | -0.859 | Destabilizing | 0.975 | D | 0.753 | deleterious | None | None | None | None | N |
| R/E | 0.9739 | likely_pathogenic | 0.965 | pathogenic | -0.666 | Destabilizing | 0.845 | D | 0.453 | neutral | None | None | None | None | N |
| R/F | 0.987 | likely_pathogenic | 0.9825 | pathogenic | -1.38 | Destabilizing | 0.996 | D | 0.8 | deleterious | None | None | None | None | N |
| R/G | 0.9725 | likely_pathogenic | 0.9624 | pathogenic | -2.298 | Highly Destabilizing | 0.954 | D | 0.66 | neutral | N | 0.489881568 | None | None | N |
| R/H | 0.4666 | ambiguous | 0.4581 | ambiguous | -2.188 | Highly Destabilizing | 0.987 | D | 0.602 | neutral | None | None | None | None | N |
| R/I | 0.9797 | likely_pathogenic | 0.9676 | pathogenic | -0.979 | Destabilizing | 0.987 | D | 0.806 | deleterious | None | None | None | None | N |
| R/K | 0.2513 | likely_benign | 0.2504 | benign | -1.535 | Destabilizing | 0.033 | N | 0.193 | neutral | None | None | None | None | N |
| R/L | 0.9279 | likely_pathogenic | 0.9043 | pathogenic | -0.979 | Destabilizing | 0.954 | D | 0.66 | neutral | N | 0.493071118 | None | None | N |
| R/M | 0.9479 | likely_pathogenic | 0.9263 | pathogenic | -1.376 | Destabilizing | 0.999 | D | 0.718 | prob.delet. | None | None | None | None | N |
| R/N | 0.9898 | likely_pathogenic | 0.9875 | pathogenic | -1.301 | Destabilizing | 0.975 | D | 0.563 | neutral | None | None | None | None | N |
| R/P | 0.9993 | likely_pathogenic | 0.999 | pathogenic | -1.292 | Destabilizing | 0.993 | D | 0.777 | deleterious | D | 0.533585269 | None | None | N |
| R/Q | 0.5188 | ambiguous | 0.4714 | ambiguous | -1.299 | Destabilizing | 0.994 | D | 0.544 | neutral | N | 0.476635477 | None | None | N |
| R/S | 0.9941 | likely_pathogenic | 0.992 | pathogenic | -2.266 | Highly Destabilizing | 0.916 | D | 0.623 | neutral | None | None | None | None | N |
| R/T | 0.9886 | likely_pathogenic | 0.9811 | pathogenic | -1.863 | Destabilizing | 0.975 | D | 0.703 | prob.neutral | None | None | None | None | N |
| R/V | 0.9824 | likely_pathogenic | 0.973 | pathogenic | -1.292 | Destabilizing | 0.975 | D | 0.786 | deleterious | None | None | None | None | N |
| R/W | 0.8666 | likely_pathogenic | 0.8315 | pathogenic | -0.859 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | N | 0.496109312 | None | None | N |
| R/Y | 0.9489 | likely_pathogenic | 0.9377 | pathogenic | -0.685 | Destabilizing | 0.996 | D | 0.785 | 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.