Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30006 | 90241;90242;90243 | chr2:178552884;178552883;178552882 | chr2:179417611;179417610;179417609 |
| N2AB | 28365 | 85318;85319;85320 | chr2:178552884;178552883;178552882 | chr2:179417611;179417610;179417609 |
| N2A | 27438 | 82537;82538;82539 | chr2:178552884;178552883;178552882 | chr2:179417611;179417610;179417609 |
| N2B | 20941 | 63046;63047;63048 | chr2:178552884;178552883;178552882 | chr2:179417611;179417610;179417609 |
| Novex-1 | 21066 | 63421;63422;63423 | chr2:178552884;178552883;178552882 | chr2:179417611;179417610;179417609 |
| Novex-2 | 21133 | 63622;63623;63624 | chr2:178552884;178552883;178552882 | chr2:179417611;179417610;179417609 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs1445678405  |
-2.161 | 1.0 | D | 0.74 | 0.544 | 0.690950808884 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs1445678405 |
-2.161 | 1.0 | D | 0.74 | 0.544 | 0.690950808884 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/G | rs1445678405 |
-2.161 | 1.0 | D | 0.74 | 0.544 | 0.690950808884 | gnomAD-4.0.0 | 3.84307E-06 | None | None | None | None | N | None | 1.69045E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78549E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9785 | likely_pathogenic | 0.9736 | pathogenic | -1.83 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | N |
| R/C | 0.6661 | likely_pathogenic | 0.596 | pathogenic | -1.756 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| R/D | 0.9977 | likely_pathogenic | 0.9974 | pathogenic | -1.154 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| R/E | 0.962 | likely_pathogenic | 0.9578 | pathogenic | -0.938 | Destabilizing | 0.999 | D | 0.69 | prob.neutral | None | None | None | None | N |
| R/F | 0.9938 | likely_pathogenic | 0.9929 | pathogenic | -0.827 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| R/G | 0.9716 | likely_pathogenic | 0.9627 | pathogenic | -2.155 | Highly Destabilizing | 1.0 | D | 0.74 | deleterious | D | 0.559250849 | None | None | N |
| R/H | 0.5448 | ambiguous | 0.5146 | ambiguous | -2.003 | Highly Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | N |
| R/I | 0.9662 | likely_pathogenic | 0.9591 | pathogenic | -0.881 | Destabilizing | 1.0 | D | 0.822 | deleterious | D | 0.527156942 | None | None | N |
| R/K | 0.491 | ambiguous | 0.4571 | ambiguous | -1.31 | Destabilizing | 0.997 | D | 0.668 | neutral | N | 0.508897649 | None | None | N |
| R/L | 0.9309 | likely_pathogenic | 0.9264 | pathogenic | -0.881 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| R/M | 0.9667 | likely_pathogenic | 0.9609 | pathogenic | -1.427 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| R/N | 0.9913 | likely_pathogenic | 0.9897 | pathogenic | -1.465 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| R/P | 0.9991 | likely_pathogenic | 0.9989 | pathogenic | -1.189 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| R/Q | 0.4735 | ambiguous | 0.4224 | ambiguous | -1.164 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| R/S | 0.9843 | likely_pathogenic | 0.9788 | pathogenic | -2.158 | Highly Destabilizing | 1.0 | D | 0.74 | deleterious | D | 0.529457439 | None | None | N |
| R/T | 0.9733 | likely_pathogenic | 0.9684 | pathogenic | -1.749 | Destabilizing | 1.0 | D | 0.748 | deleterious | N | 0.510138643 | None | None | N |
| R/V | 0.9681 | likely_pathogenic | 0.9616 | pathogenic | -1.189 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| R/W | 0.9054 | likely_pathogenic | 0.8875 | pathogenic | -0.506 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| R/Y | 0.9753 | likely_pathogenic | 0.9697 | pathogenic | -0.393 | Destabilizing | 1.0 | D | 0.833 | 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.