Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15020 | 45283;45284;45285 | chr2:178621864;178621863;178621862 | chr2:179486591;179486590;179486589 |
| N2AB | 13379 | 40360;40361;40362 | chr2:178621864;178621863;178621862 | chr2:179486591;179486590;179486589 |
| N2A | 12452 | 37579;37580;37581 | chr2:178621864;178621863;178621862 | chr2:179486591;179486590;179486589 |
| N2B | 5955 | 18088;18089;18090 | chr2:178621864;178621863;178621862 | chr2:179486591;179486590;179486589 |
| Novex-1 | 6080 | 18463;18464;18465 | chr2:178621864;178621863;178621862 | chr2:179486591;179486590;179486589 |
| Novex-2 | 6147 | 18664;18665;18666 | chr2:178621864;178621863;178621862 | chr2:179486591;179486590;179486589 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/N | rs755201448  |
-0.559 | 0.961 | D | 0.662 | 0.368 | 0.256793551483 | gnomAD-2.1.1 | 5.25E-05 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 3.93005E-04 | None | 0 | 0 | 0 |
| T/N | rs755201448 |
-0.559 | 0.961 | D | 0.662 | 0.368 | 0.256793551483 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 6.21633E-04 | 0 |
| T/N | rs755201448 |
-0.559 | 0.961 | D | 0.662 | 0.368 | 0.256793551483 | gnomAD-4.0.0 | 2.54344E-05 | None | None | None | None | N | None | 1.33676E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.06665E-04 | 4.81139E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.3711 | ambiguous | 0.3039 | benign | -1.131 | Destabilizing | 0.835 | D | 0.537 | neutral | N | 0.458661117 | None | None | N |
| T/C | 0.8333 | likely_pathogenic | 0.7383 | pathogenic | -0.549 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| T/D | 0.9418 | likely_pathogenic | 0.9261 | pathogenic | -0.377 | Destabilizing | 0.97 | D | 0.689 | prob.neutral | None | None | None | None | N |
| T/E | 0.9358 | likely_pathogenic | 0.9185 | pathogenic | -0.289 | Destabilizing | 0.97 | D | 0.685 | prob.neutral | None | None | None | None | N |
| T/F | 0.9264 | likely_pathogenic | 0.8928 | pathogenic | -0.891 | Destabilizing | 0.999 | D | 0.769 | deleterious | None | None | None | None | N |
| T/G | 0.6792 | likely_pathogenic | 0.6595 | pathogenic | -1.48 | Destabilizing | 0.97 | D | 0.674 | neutral | None | None | None | None | N |
| T/H | 0.8907 | likely_pathogenic | 0.8767 | pathogenic | -1.533 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| T/I | 0.8903 | likely_pathogenic | 0.8213 | pathogenic | -0.255 | Destabilizing | 0.994 | D | 0.739 | prob.delet. | D | 0.575827254 | None | None | N |
| T/K | 0.9329 | likely_pathogenic | 0.929 | pathogenic | -0.647 | Destabilizing | 0.97 | D | 0.688 | prob.neutral | None | None | None | None | N |
| T/L | 0.7478 | likely_pathogenic | 0.6539 | pathogenic | -0.255 | Destabilizing | 0.985 | D | 0.649 | neutral | None | None | None | None | N |
| T/M | 0.5643 | likely_pathogenic | 0.4727 | ambiguous | -0.02 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| T/N | 0.634 | likely_pathogenic | 0.6192 | pathogenic | -0.821 | Destabilizing | 0.961 | D | 0.662 | neutral | D | 0.577164632 | None | None | N |
| T/P | 0.8987 | likely_pathogenic | 0.8855 | pathogenic | -0.515 | Destabilizing | 0.994 | D | 0.74 | deleterious | D | 0.578651479 | None | None | N |
| T/Q | 0.8901 | likely_pathogenic | 0.87 | pathogenic | -0.83 | Destabilizing | 0.996 | D | 0.765 | deleterious | None | None | None | None | N |
| T/R | 0.9163 | likely_pathogenic | 0.9071 | pathogenic | -0.542 | Destabilizing | 0.996 | D | 0.737 | prob.delet. | None | None | None | None | N |
| T/S | 0.2522 | likely_benign | 0.2369 | benign | -1.194 | Destabilizing | 0.287 | N | 0.352 | neutral | N | 0.438165317 | None | None | N |
| T/V | 0.7448 | likely_pathogenic | 0.6341 | pathogenic | -0.515 | Destabilizing | 0.985 | D | 0.632 | neutral | None | None | None | None | N |
| T/W | 0.9842 | likely_pathogenic | 0.9777 | pathogenic | -0.833 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| T/Y | 0.9266 | likely_pathogenic | 0.9017 | pathogenic | -0.591 | Destabilizing | 0.999 | D | 0.777 | 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.