Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16003 | 48232;48233;48234 | chr2:178616882;178616881;178616880 | chr2:179481609;179481608;179481607 |
| N2AB | 14362 | 43309;43310;43311 | chr2:178616882;178616881;178616880 | chr2:179481609;179481608;179481607 |
| N2A | 13435 | 40528;40529;40530 | chr2:178616882;178616881;178616880 | chr2:179481609;179481608;179481607 |
| N2B | 6938 | 21037;21038;21039 | chr2:178616882;178616881;178616880 | chr2:179481609;179481608;179481607 |
| Novex-1 | 7063 | 21412;21413;21414 | chr2:178616882;178616881;178616880 | chr2:179481609;179481608;179481607 |
| Novex-2 | 7130 | 21613;21614;21615 | chr2:178616882;178616881;178616880 | chr2:179481609;179481608;179481607 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | None | None | 1.0 | D | 0.855 | 0.815 | 0.882631419571 | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25001E-06 | 0 | 0 |
| L/Q | None | None | 1.0 | D | 0.843 | 0.741 | 0.865776962991 | 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 |
| L/V | rs2057435280  |
None | 0.999 | N | 0.511 | 0.415 | 0.622486987839 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.6524 | likely_pathogenic | 0.6398 | pathogenic | -2.23 | Highly Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | N |
| L/C | 0.8028 | likely_pathogenic | 0.794 | pathogenic | -1.499 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| L/D | 0.9825 | likely_pathogenic | 0.9814 | pathogenic | -2.246 | Highly Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| L/E | 0.8803 | likely_pathogenic | 0.8713 | pathogenic | -2.091 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| L/F | 0.3838 | ambiguous | 0.3752 | ambiguous | -1.363 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| L/G | 0.9198 | likely_pathogenic | 0.9202 | pathogenic | -2.69 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| L/H | 0.8119 | likely_pathogenic | 0.8113 | pathogenic | -1.861 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| L/I | 0.1283 | likely_benign | 0.1197 | benign | -0.944 | Destabilizing | 0.999 | D | 0.51 | neutral | N | 0.51914663 | None | None | N |
| L/K | 0.7838 | likely_pathogenic | 0.7823 | pathogenic | -1.799 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/M | 0.2178 | likely_benign | 0.2077 | benign | -0.815 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| L/N | 0.9367 | likely_pathogenic | 0.9382 | pathogenic | -1.965 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| L/P | 0.8285 | likely_pathogenic | 0.8286 | pathogenic | -1.349 | Destabilizing | 1.0 | D | 0.855 | deleterious | D | 0.684684796 | None | None | N |
| L/Q | 0.669 | likely_pathogenic | 0.6767 | pathogenic | -1.949 | Destabilizing | 1.0 | D | 0.843 | deleterious | D | 0.685113798 | None | None | N |
| L/R | 0.7008 | likely_pathogenic | 0.7042 | pathogenic | -1.336 | Destabilizing | 1.0 | D | 0.851 | deleterious | D | 0.684684796 | None | None | N |
| L/S | 0.8832 | likely_pathogenic | 0.8757 | pathogenic | -2.611 | Highly Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| L/T | 0.664 | likely_pathogenic | 0.6476 | pathogenic | -2.314 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| L/V | 0.1509 | likely_benign | 0.1424 | benign | -1.349 | Destabilizing | 0.999 | D | 0.511 | neutral | N | 0.520720721 | None | None | N |
| L/W | 0.6805 | likely_pathogenic | 0.679 | pathogenic | -1.591 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| L/Y | 0.8164 | likely_pathogenic | 0.8131 | pathogenic | -1.328 | Destabilizing | 1.0 | D | 0.829 | 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.