Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23417 | 70474;70475;70476 | chr2:178575883;178575882;178575881 | chr2:179440610;179440609;179440608 |
| N2AB | 21776 | 65551;65552;65553 | chr2:178575883;178575882;178575881 | chr2:179440610;179440609;179440608 |
| N2A | 20849 | 62770;62771;62772 | chr2:178575883;178575882;178575881 | chr2:179440610;179440609;179440608 |
| N2B | 14352 | 43279;43280;43281 | chr2:178575883;178575882;178575881 | chr2:179440610;179440609;179440608 |
| Novex-1 | 14477 | 43654;43655;43656 | chr2:178575883;178575882;178575881 | chr2:179440610;179440609;179440608 |
| Novex-2 | 14544 | 43855;43856;43857 | chr2:178575883;178575882;178575881 | chr2:179440610;179440609;179440608 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs201836227  |
-2.502 | 0.549 | N | 0.617 | 0.341 | None | gnomAD-2.1.1 | 3.14059E-04 | None | None | None | None | N | None | 3.43401E-03 | 0 | None | 0 | 5.13E-05 | None | 0 | None | 0 | 3.12E-05 | 0 |
| I/T | rs201836227 |
-2.502 | 0.549 | N | 0.617 | 0.341 | None | gnomAD-3.1.2 | 7.43382E-04 | None | None | None | None | N | None | 2.65765E-03 | 1.31044E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs201836227 |
-2.502 | 0.549 | N | 0.617 | 0.341 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/T | rs201836227 |
-2.502 | 0.549 | N | 0.617 | 0.341 | None | gnomAD-4.0.0 | 1.58661E-04 | None | None | None | None | N | None | 3.01462E-03 | 6.66644E-05 | None | 0 | 2.23075E-05 | None | 0 | 0 | 1.6955E-05 | 0 | 8.00359E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3523 | ambiguous | 0.385 | ambiguous | -2.376 | Highly Destabilizing | 0.25 | N | 0.551 | neutral | None | None | None | None | N |
| I/C | 0.8318 | likely_pathogenic | 0.8848 | pathogenic | -1.752 | Destabilizing | 0.972 | D | 0.713 | prob.delet. | None | None | None | None | N |
| I/D | 0.9972 | likely_pathogenic | 0.9982 | pathogenic | -2.555 | Highly Destabilizing | 0.972 | D | 0.785 | deleterious | None | None | None | None | N |
| I/E | 0.9917 | likely_pathogenic | 0.993 | pathogenic | -2.489 | Highly Destabilizing | 0.92 | D | 0.769 | deleterious | None | None | None | None | N |
| I/F | 0.7494 | likely_pathogenic | 0.8362 | pathogenic | -1.682 | Destabilizing | 0.549 | D | 0.595 | neutral | N | 0.505219582 | None | None | N |
| I/G | 0.941 | likely_pathogenic | 0.9583 | pathogenic | -2.787 | Highly Destabilizing | 0.766 | D | 0.75 | deleterious | None | None | None | None | N |
| I/H | 0.9946 | likely_pathogenic | 0.997 | pathogenic | -2.086 | Highly Destabilizing | 0.992 | D | 0.765 | deleterious | None | None | None | None | N |
| I/K | 0.9912 | likely_pathogenic | 0.9938 | pathogenic | -1.844 | Destabilizing | 0.766 | D | 0.75 | deleterious | None | None | None | None | N |
| I/L | 0.1038 | likely_benign | 0.1347 | benign | -1.256 | Destabilizing | 0.001 | N | 0.267 | neutral | N | 0.34489235 | None | None | N |
| I/M | 0.1336 | likely_benign | 0.1749 | benign | -1.034 | Destabilizing | 0.81 | D | 0.619 | neutral | N | 0.475590108 | None | None | N |
| I/N | 0.9742 | likely_pathogenic | 0.9824 | pathogenic | -1.812 | Destabilizing | 0.963 | D | 0.791 | deleterious | N | 0.50539294 | None | None | N |
| I/P | 0.9936 | likely_pathogenic | 0.9951 | pathogenic | -1.604 | Destabilizing | 0.972 | D | 0.787 | deleterious | None | None | None | None | N |
| I/Q | 0.9841 | likely_pathogenic | 0.9887 | pathogenic | -1.947 | Destabilizing | 0.972 | D | 0.794 | deleterious | None | None | None | None | N |
| I/R | 0.9847 | likely_pathogenic | 0.9894 | pathogenic | -1.248 | Destabilizing | 0.92 | D | 0.786 | deleterious | None | None | None | None | N |
| I/S | 0.8313 | likely_pathogenic | 0.867 | pathogenic | -2.429 | Highly Destabilizing | 0.549 | D | 0.694 | prob.neutral | N | 0.504872865 | None | None | N |
| I/T | 0.4703 | ambiguous | 0.4374 | ambiguous | -2.241 | Highly Destabilizing | 0.549 | D | 0.617 | neutral | N | 0.486017746 | None | None | N |
| I/V | 0.076 | likely_benign | 0.0824 | benign | -1.604 | Destabilizing | 0.002 | N | 0.251 | neutral | N | 0.372398665 | None | None | N |
| I/W | 0.9943 | likely_pathogenic | 0.9971 | pathogenic | -1.883 | Destabilizing | 0.992 | D | 0.763 | deleterious | None | None | None | None | N |
| I/Y | 0.9852 | likely_pathogenic | 0.9915 | pathogenic | -1.676 | Destabilizing | 0.92 | D | 0.728 | prob.delet. | 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.