Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30298 | 91117;91118;91119 | chr2:178552008;178552007;178552006 | chr2:179416735;179416734;179416733 |
| N2AB | 28657 | 86194;86195;86196 | chr2:178552008;178552007;178552006 | chr2:179416735;179416734;179416733 |
| N2A | 27730 | 83413;83414;83415 | chr2:178552008;178552007;178552006 | chr2:179416735;179416734;179416733 |
| N2B | 21233 | 63922;63923;63924 | chr2:178552008;178552007;178552006 | chr2:179416735;179416734;179416733 |
| Novex-1 | 21358 | 64297;64298;64299 | chr2:178552008;178552007;178552006 | chr2:179416735;179416734;179416733 |
| Novex-2 | 21425 | 64498;64499;64500 | chr2:178552008;178552007;178552006 | chr2:179416735;179416734;179416733 |
| 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 | None | None | 1.0 | D | 0.711 | 0.626 | 0.798263818159 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| R/S | rs751088273  |
None | 1.0 | N | 0.724 | 0.571 | 0.52891208781 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-06 | 0 | 0 |
| R/T | rs767538180 |
-1.82 | 1.0 | N | 0.729 | 0.557 | 0.799582421018 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| R/T | rs767538180 |
-1.82 | 1.0 | N | 0.729 | 0.557 | 0.799582421018 | gnomAD-4.0.0 | 1.36941E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16058E-05 | 1.65782E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9517 | likely_pathogenic | 0.9404 | pathogenic | -1.771 | Destabilizing | 0.999 | D | 0.583 | neutral | None | None | None | None | N |
| R/C | 0.5192 | ambiguous | 0.4836 | ambiguous | -1.785 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| R/D | 0.9972 | likely_pathogenic | 0.9972 | pathogenic | -1.017 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| R/E | 0.9508 | likely_pathogenic | 0.9496 | pathogenic | -0.796 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | N |
| R/F | 0.9799 | likely_pathogenic | 0.9771 | pathogenic | -0.955 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| R/G | 0.9704 | likely_pathogenic | 0.9659 | pathogenic | -2.116 | Highly Destabilizing | 1.0 | D | 0.711 | prob.delet. | D | 0.550034137 | None | None | N |
| R/H | 0.5407 | ambiguous | 0.5334 | ambiguous | -2.003 | Highly Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| R/I | 0.8598 | likely_pathogenic | 0.838 | pathogenic | -0.773 | Destabilizing | 1.0 | D | 0.841 | deleterious | D | 0.52946112 | None | None | N |
| R/K | 0.5038 | ambiguous | 0.4924 | ambiguous | -1.248 | Destabilizing | 0.997 | D | 0.611 | neutral | N | 0.494907997 | None | None | N |
| R/L | 0.8555 | likely_pathogenic | 0.8301 | pathogenic | -0.773 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| R/M | 0.9007 | likely_pathogenic | 0.8821 | pathogenic | -1.361 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| R/N | 0.9865 | likely_pathogenic | 0.9854 | pathogenic | -1.36 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| R/P | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -1.095 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| R/Q | 0.3759 | ambiguous | 0.3786 | ambiguous | -1.139 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| R/S | 0.9745 | likely_pathogenic | 0.9705 | pathogenic | -2.129 | Highly Destabilizing | 1.0 | D | 0.724 | prob.delet. | N | 0.517278213 | None | None | N |
| R/T | 0.9438 | likely_pathogenic | 0.934 | pathogenic | -1.699 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.507340713 | None | None | N |
| R/V | 0.8921 | likely_pathogenic | 0.8761 | pathogenic | -1.095 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| R/W | 0.8232 | likely_pathogenic | 0.8179 | pathogenic | -0.559 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| R/Y | 0.9515 | likely_pathogenic | 0.9446 | pathogenic | -0.392 | Destabilizing | 1.0 | D | 0.825 | 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.