Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4755 | 14488;14489;14490 | chr2:178738190;178738189;178738188 | chr2:179602917;179602916;179602915 |
| N2AB | 4438 | 13537;13538;13539 | chr2:178738190;178738189;178738188 | chr2:179602917;179602916;179602915 |
| N2A | 3511 | 10756;10757;10758 | chr2:178738190;178738189;178738188 | chr2:179602917;179602916;179602915 |
| N2B | 4392 | 13399;13400;13401 | chr2:178738190;178738189;178738188 | chr2:179602917;179602916;179602915 |
| Novex-1 | 4517 | 13774;13775;13776 | chr2:178738190;178738189;178738188 | chr2:179602917;179602916;179602915 |
| Novex-2 | 4584 | 13975;13976;13977 | chr2:178738190;178738189;178738188 | chr2:179602917;179602916;179602915 |
| 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/C | rs767410813  |
-0.427 | 0.931 | N | 0.773 | 0.377 | 0.302459207581 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| S/C | rs767410813 |
-0.427 | 0.931 | N | 0.773 | 0.377 | 0.302459207581 | gnomAD-4.0.0 | 2.05274E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.47818E-05 | 0 |
| S/F | None | None | 0.781 | N | 0.805 | 0.411 | 0.438383285633 | gnomAD-4.0.0 | 6.84245E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99473E-07 | 0 | 0 |
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 | 0.1612 | likely_benign | 0.1793 | benign | -1.05 | Destabilizing | 0.094 | N | 0.594 | neutral | N | 0.440193694 | None | None | N |
| S/C | 0.1927 | likely_benign | 0.1929 | benign | -0.658 | Destabilizing | 0.931 | D | 0.773 | deleterious | N | 0.444966846 | None | None | N |
| S/D | 0.9563 | likely_pathogenic | 0.9628 | pathogenic | -0.973 | Destabilizing | 0.399 | N | 0.682 | prob.neutral | None | None | None | None | N |
| S/E | 0.9813 | likely_pathogenic | 0.9818 | pathogenic | -0.836 | Destabilizing | 0.399 | N | 0.679 | prob.neutral | None | None | None | None | N |
| S/F | 0.7251 | likely_pathogenic | 0.777 | pathogenic | -1.038 | Destabilizing | 0.781 | D | 0.805 | deleterious | N | 0.442040291 | None | None | N |
| S/G | 0.2937 | likely_benign | 0.3331 | benign | -1.376 | Destabilizing | 0.399 | N | 0.672 | neutral | None | None | None | None | N |
| S/H | 0.8384 | likely_pathogenic | 0.7883 | pathogenic | -1.59 | Destabilizing | 0.982 | D | 0.771 | deleterious | None | None | None | None | N |
| S/I | 0.6692 | likely_pathogenic | 0.7372 | pathogenic | -0.235 | Destabilizing | 0.539 | D | 0.802 | deleterious | None | None | None | None | N |
| S/K | 0.9931 | likely_pathogenic | 0.9937 | pathogenic | -0.126 | Destabilizing | 0.399 | N | 0.684 | prob.neutral | None | None | None | None | N |
| S/L | 0.3662 | ambiguous | 0.4518 | ambiguous | -0.235 | Destabilizing | 0.25 | N | 0.765 | deleterious | None | None | None | None | N |
| S/M | 0.5699 | likely_pathogenic | 0.6415 | pathogenic | -0.168 | Destabilizing | 0.947 | D | 0.773 | deleterious | None | None | None | None | N |
| S/N | 0.6847 | likely_pathogenic | 0.7168 | pathogenic | -0.565 | Destabilizing | 0.399 | N | 0.683 | prob.neutral | None | None | None | None | N |
| S/P | 0.9605 | likely_pathogenic | 0.98 | pathogenic | -0.476 | Destabilizing | 0.781 | D | 0.789 | deleterious | N | 0.445593322 | None | None | N |
| S/Q | 0.9488 | likely_pathogenic | 0.9465 | pathogenic | -0.53 | Destabilizing | 0.826 | D | 0.753 | deleterious | None | None | None | None | N |
| S/R | 0.983 | likely_pathogenic | 0.9833 | pathogenic | -0.319 | Destabilizing | 0.7 | D | 0.791 | deleterious | None | None | None | None | N |
| S/T | 0.0904 | likely_benign | 0.1296 | benign | -0.437 | Destabilizing | 0.002 | N | 0.461 | neutral | N | 0.441266413 | None | None | N |
| S/V | 0.5392 | ambiguous | 0.617 | pathogenic | -0.476 | Destabilizing | 0.539 | D | 0.789 | deleterious | None | None | None | None | N |
| S/W | 0.8353 | likely_pathogenic | 0.8393 | pathogenic | -1.099 | Destabilizing | 0.982 | D | 0.797 | deleterious | None | None | None | None | N |
| S/Y | 0.6809 | likely_pathogenic | 0.6756 | pathogenic | -0.731 | Destabilizing | 0.781 | D | 0.805 | deleterious | N | 0.442668446 | 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.