Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31717 | 95374;95375;95376 | chr2:178546087;178546086;178546085 | chr2:179410814;179410813;179410812 |
| N2AB | 30076 | 90451;90452;90453 | chr2:178546087;178546086;178546085 | chr2:179410814;179410813;179410812 |
| N2A | 29149 | 87670;87671;87672 | chr2:178546087;178546086;178546085 | chr2:179410814;179410813;179410812 |
| N2B | 22652 | 68179;68180;68181 | chr2:178546087;178546086;178546085 | chr2:179410814;179410813;179410812 |
| Novex-1 | 22777 | 68554;68555;68556 | chr2:178546087;178546086;178546085 | chr2:179410814;179410813;179410812 |
| Novex-2 | 22844 | 68755;68756;68757 | chr2:178546087;178546086;178546085 | chr2:179410814;179410813;179410812 |
| 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/I | rs150930737  |
-0.378 | 0.003 | N | 0.141 | 0.084 | None | gnomAD-2.1.1 | 6.85E-05 | None | None | None | None | N | None | 4.14E-05 | 8.52E-05 | None | 0 | 0 | None | 3.31E-05 | None | 0 | 1.10751E-04 | 0 |
| V/I | rs150930737 |
-0.378 | 0.003 | N | 0.141 | 0.084 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 2.41E-05 | 1.30873E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 2.07297E-04 | 0 |
| V/I | rs150930737 |
-0.378 | 0.003 | N | 0.141 | 0.084 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/I | rs150930737 |
-0.378 | 0.003 | N | 0.141 | 0.084 | None | gnomAD-4.0.0 | 3.53841E-05 | None | None | None | None | N | None | 9.33607E-05 | 8.34251E-05 | None | 0 | 0 | None | 1.56573E-05 | 1.65453E-04 | 2.54709E-05 | 8.81154E-05 | 8.01847E-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 | 0.3259 | likely_benign | 0.3717 | ambiguous | -1.331 | Destabilizing | 0.296 | N | 0.54 | neutral | N | 0.510227465 | None | None | N |
| V/C | 0.7292 | likely_pathogenic | 0.7609 | pathogenic | -1.153 | Destabilizing | 0.991 | D | 0.687 | prob.neutral | None | None | None | None | N |
| V/D | 0.9017 | likely_pathogenic | 0.9335 | pathogenic | -0.567 | Destabilizing | 0.879 | D | 0.819 | deleterious | D | 0.545718951 | None | None | N |
| V/E | 0.835 | likely_pathogenic | 0.8743 | pathogenic | -0.534 | Destabilizing | 0.906 | D | 0.761 | deleterious | None | None | None | None | N |
| V/F | 0.2647 | likely_benign | 0.3288 | benign | -0.946 | Destabilizing | 0.901 | D | 0.692 | prob.neutral | N | 0.511075614 | None | None | N |
| V/G | 0.5808 | likely_pathogenic | 0.6568 | pathogenic | -1.683 | Destabilizing | 0.879 | D | 0.791 | deleterious | N | 0.510471492 | None | None | N |
| V/H | 0.8854 | likely_pathogenic | 0.9208 | pathogenic | -1.203 | Destabilizing | 0.991 | D | 0.803 | deleterious | None | None | None | None | N |
| V/I | 0.0657 | likely_benign | 0.0709 | benign | -0.461 | Destabilizing | 0.003 | N | 0.141 | neutral | N | 0.46455389 | None | None | N |
| V/K | 0.8395 | likely_pathogenic | 0.8824 | pathogenic | -1.009 | Destabilizing | 0.906 | D | 0.764 | deleterious | None | None | None | None | N |
| V/L | 0.2301 | likely_benign | 0.279 | benign | -0.461 | Destabilizing | 0.074 | N | 0.355 | neutral | N | 0.478956563 | None | None | N |
| V/M | 0.2375 | likely_benign | 0.2712 | benign | -0.523 | Destabilizing | 0.826 | D | 0.598 | neutral | None | None | None | None | N |
| V/N | 0.7279 | likely_pathogenic | 0.8039 | pathogenic | -0.846 | Destabilizing | 0.967 | D | 0.839 | deleterious | None | None | None | None | N |
| V/P | 0.6371 | likely_pathogenic | 0.7004 | pathogenic | -0.715 | Destabilizing | 0.967 | D | 0.784 | deleterious | None | None | None | None | N |
| V/Q | 0.8023 | likely_pathogenic | 0.8497 | pathogenic | -0.901 | Destabilizing | 0.967 | D | 0.777 | deleterious | None | None | None | None | N |
| V/R | 0.7877 | likely_pathogenic | 0.8465 | pathogenic | -0.672 | Destabilizing | 0.906 | D | 0.837 | deleterious | None | None | None | None | N |
| V/S | 0.5516 | ambiguous | 0.6197 | pathogenic | -1.504 | Destabilizing | 0.906 | D | 0.738 | prob.delet. | None | None | None | None | N |
| V/T | 0.4398 | ambiguous | 0.482 | ambiguous | -1.33 | Destabilizing | 0.575 | D | 0.554 | neutral | None | None | None | None | N |
| V/W | 0.9109 | likely_pathogenic | 0.9426 | pathogenic | -1.102 | Destabilizing | 0.991 | D | 0.811 | deleterious | None | None | None | None | N |
| V/Y | 0.7179 | likely_pathogenic | 0.8005 | pathogenic | -0.797 | Destabilizing | 0.906 | D | 0.706 | 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.