Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22732 | 68419;68420;68421 | chr2:178578836;178578835;178578834 | chr2:179443563;179443562;179443561 |
| N2AB | 21091 | 63496;63497;63498 | chr2:178578836;178578835;178578834 | chr2:179443563;179443562;179443561 |
| N2A | 20164 | 60715;60716;60717 | chr2:178578836;178578835;178578834 | chr2:179443563;179443562;179443561 |
| N2B | 13667 | 41224;41225;41226 | chr2:178578836;178578835;178578834 | chr2:179443563;179443562;179443561 |
| Novex-1 | 13792 | 41599;41600;41601 | chr2:178578836;178578835;178578834 | chr2:179443563;179443562;179443561 |
| Novex-2 | 13859 | 41800;41801;41802 | chr2:178578836;178578835;178578834 | chr2:179443563;179443562;179443561 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs727505352  |
0.454 | 0.915 | N | 0.713 | 0.45 | 0.590137622951 | gnomAD-2.1.1 | 1.49507E-04 | None | None | None | None | N | None | 0 | 9.61875E-04 | None | 0 | 1.11782E-04 | None | 3.31E-05 | None | 0 | 0 | 1.66889E-04 |
| S/L | rs727505352 |
0.454 | 0.915 | N | 0.713 | 0.45 | 0.590137622951 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/L | rs727505352 |
0.454 | 0.915 | N | 0.713 | 0.45 | 0.590137622951 | gnomAD-4.0.0 | 3.59926E-05 | None | None | None | None | N | None | 6.68413E-05 | 6.18398E-04 | None | 0 | 8.93256E-05 | None | 0 | 0 | 3.3943E-06 | 4.40937E-05 | 6.41355E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.4509 | ambiguous | 0.4743 | ambiguous | -0.412 | Destabilizing | 0.012 | N | 0.266 | neutral | N | 0.492611181 | None | None | N |
| S/C | 0.5438 | ambiguous | 0.5933 | pathogenic | -0.15 | Destabilizing | 0.993 | D | 0.724 | deleterious | None | None | None | None | N |
| S/D | 0.9742 | likely_pathogenic | 0.9691 | pathogenic | -0.47 | Destabilizing | 0.911 | D | 0.63 | neutral | None | None | None | None | N |
| S/E | 0.9912 | likely_pathogenic | 0.9892 | pathogenic | -0.303 | Destabilizing | 0.835 | D | 0.612 | neutral | None | None | None | None | N |
| S/F | 0.9877 | likely_pathogenic | 0.9868 | pathogenic | -0.33 | Destabilizing | 0.973 | D | 0.831 | deleterious | None | None | None | None | N |
| S/G | 0.4231 | ambiguous | 0.4493 | ambiguous | -0.801 | Destabilizing | 0.717 | D | 0.562 | neutral | None | None | None | None | N |
| S/H | 0.9838 | likely_pathogenic | 0.9837 | pathogenic | -1.129 | Destabilizing | 0.998 | D | 0.723 | deleterious | None | None | None | None | N |
| S/I | 0.9555 | likely_pathogenic | 0.957 | pathogenic | 0.56 | Stabilizing | 0.947 | D | 0.819 | deleterious | None | None | None | None | N |
| S/K | 0.9984 | likely_pathogenic | 0.9983 | pathogenic | 0.055 | Stabilizing | 0.835 | D | 0.587 | neutral | None | None | None | None | N |
| S/L | 0.8489 | likely_pathogenic | 0.8657 | pathogenic | 0.56 | Stabilizing | 0.915 | D | 0.713 | prob.delet. | N | 0.502739719 | None | None | N |
| S/M | 0.8594 | likely_pathogenic | 0.8679 | pathogenic | 0.39 | Stabilizing | 0.998 | D | 0.72 | deleterious | None | None | None | None | N |
| S/N | 0.9265 | likely_pathogenic | 0.9281 | pathogenic | -0.514 | Destabilizing | 0.973 | D | 0.658 | prob.neutral | None | None | None | None | N |
| S/P | 0.9929 | likely_pathogenic | 0.9914 | pathogenic | 0.273 | Stabilizing | 0.964 | D | 0.729 | deleterious | N | 0.495613376 | None | None | N |
| S/Q | 0.9901 | likely_pathogenic | 0.9902 | pathogenic | -0.277 | Destabilizing | 0.973 | D | 0.698 | prob.delet. | None | None | None | None | N |
| S/R | 0.9981 | likely_pathogenic | 0.9979 | pathogenic | -0.323 | Destabilizing | 0.973 | D | 0.735 | deleterious | None | None | None | None | N |
| S/T | 0.277 | likely_benign | 0.2724 | benign | -0.271 | Destabilizing | 0.792 | D | 0.563 | neutral | N | 0.495189015 | None | None | N |
| S/V | 0.9017 | likely_pathogenic | 0.9087 | pathogenic | 0.273 | Stabilizing | 0.899 | D | 0.76 | deleterious | None | None | None | None | N |
| S/W | 0.9839 | likely_pathogenic | 0.9822 | pathogenic | -0.564 | Destabilizing | 0.999 | D | 0.799 | deleterious | D | 0.53413929 | None | None | N |
| S/Y | 0.9768 | likely_pathogenic | 0.9746 | pathogenic | -0.081 | Destabilizing | 0.991 | D | 0.827 | 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.