Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35031 | 105316;105317;105318 | chr2:178531524;178531523;178531522 | chr2:179396251;179396250;179396249 |
| N2AB | 33390 | 100393;100394;100395 | chr2:178531524;178531523;178531522 | chr2:179396251;179396250;179396249 |
| N2A | 32463 | 97612;97613;97614 | chr2:178531524;178531523;178531522 | chr2:179396251;179396250;179396249 |
| N2B | 25966 | 78121;78122;78123 | chr2:178531524;178531523;178531522 | chr2:179396251;179396250;179396249 |
| Novex-1 | 26091 | 78496;78497;78498 | chr2:178531524;178531523;178531522 | chr2:179396251;179396250;179396249 |
| Novex-2 | 26158 | 78697;78698;78699 | chr2:178531524;178531523;178531522 | chr2:179396251;179396250;179396249 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | None | None | 0.889 | D | 0.631 | 0.54 | 0.726351811296 | gnomAD-4.0.0 | 6.84169E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99397E-07 | 0 | 0 |
| V/M | rs552058608  |
-1.063 | 0.997 | D | 0.719 | 0.559 | None | gnomAD-2.1.1 | 4.99E-05 | None | None | None | None | N | None | 2.47975E-04 | 0 | None | 0 | 1.02428E-04 | None | 9.8E-05 | None | 0 | 2.34E-05 | 0 |
| V/M | rs552058608 |
-1.063 | 0.997 | D | 0.719 | 0.559 | None | gnomAD-3.1.2 | 8.54E-05 | None | None | None | None | N | None | 2.65354E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/M | rs552058608 |
-1.063 | 0.997 | D | 0.719 | 0.559 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| V/M | rs552058608 |
-1.063 | 0.997 | D | 0.719 | 0.559 | None | gnomAD-4.0.0 | 3.77954E-05 | None | None | None | None | N | None | 2.39827E-04 | 0 | None | 0 | 6.68419E-05 | None | 0 | 0 | 2.11884E-05 | 1.42732E-04 | 3.20072E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.9022 | likely_pathogenic | 0.928 | pathogenic | -1.485 | Destabilizing | 0.939 | D | 0.604 | neutral | D | 0.61178556 | None | None | N |
| V/C | 0.9793 | likely_pathogenic | 0.9807 | pathogenic | -1.576 | Destabilizing | 0.999 | D | 0.704 | prob.neutral | None | None | None | None | N |
| V/D | 0.9954 | likely_pathogenic | 0.9965 | pathogenic | -2.661 | Highly Destabilizing | 0.998 | D | 0.729 | prob.delet. | None | None | None | None | N |
| V/E | 0.9877 | likely_pathogenic | 0.9901 | pathogenic | -2.658 | Highly Destabilizing | 0.997 | D | 0.702 | prob.neutral | D | 0.612390973 | None | None | N |
| V/F | 0.9408 | likely_pathogenic | 0.9295 | pathogenic | -1.371 | Destabilizing | 0.986 | D | 0.703 | prob.neutral | None | None | None | None | N |
| V/G | 0.9501 | likely_pathogenic | 0.9596 | pathogenic | -1.769 | Destabilizing | 0.997 | D | 0.709 | prob.delet. | D | 0.612390973 | None | None | N |
| V/H | 0.9975 | likely_pathogenic | 0.9979 | pathogenic | -1.268 | Destabilizing | 0.999 | D | 0.714 | prob.delet. | None | None | None | None | N |
| V/I | 0.1372 | likely_benign | 0.1368 | benign | -0.786 | Destabilizing | 0.06 | N | 0.462 | neutral | None | None | None | None | N |
| V/K | 0.991 | likely_pathogenic | 0.9926 | pathogenic | -1.29 | Destabilizing | 0.993 | D | 0.703 | prob.neutral | None | None | None | None | N |
| V/L | 0.8804 | likely_pathogenic | 0.8677 | pathogenic | -0.786 | Destabilizing | 0.889 | D | 0.631 | neutral | D | 0.593748157 | None | None | N |
| V/M | 0.8242 | likely_pathogenic | 0.8089 | pathogenic | -0.759 | Destabilizing | 0.997 | D | 0.719 | prob.delet. | D | 0.611987365 | None | None | N |
| V/N | 0.9852 | likely_pathogenic | 0.9882 | pathogenic | -1.38 | Destabilizing | 0.998 | D | 0.735 | prob.delet. | None | None | None | None | N |
| V/P | 0.9934 | likely_pathogenic | 0.9945 | pathogenic | -0.989 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | None | None | None | None | N |
| V/Q | 0.9913 | likely_pathogenic | 0.9919 | pathogenic | -1.638 | Destabilizing | 0.998 | D | 0.719 | prob.delet. | None | None | None | None | N |
| V/R | 0.985 | likely_pathogenic | 0.9866 | pathogenic | -0.756 | Destabilizing | 0.998 | D | 0.733 | prob.delet. | None | None | None | None | N |
| V/S | 0.9635 | likely_pathogenic | 0.9746 | pathogenic | -1.745 | Destabilizing | 0.993 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/T | 0.8897 | likely_pathogenic | 0.9176 | pathogenic | -1.644 | Destabilizing | 0.953 | D | 0.673 | neutral | None | None | None | None | N |
| V/W | 0.9991 | likely_pathogenic | 0.999 | pathogenic | -1.604 | Destabilizing | 0.999 | D | 0.682 | prob.neutral | None | None | None | None | N |
| V/Y | 0.9945 | likely_pathogenic | 0.9945 | pathogenic | -1.256 | Destabilizing | 0.998 | D | 0.707 | prob.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.