Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2401 | 7426;7427;7428 | chr2:178773967;178773966;178773965 | chr2:179638694;179638693;179638692 |
| N2AB | 2401 | 7426;7427;7428 | chr2:178773967;178773966;178773965 | chr2:179638694;179638693;179638692 |
| N2A | 2401 | 7426;7427;7428 | chr2:178773967;178773966;178773965 | chr2:179638694;179638693;179638692 |
| N2B | 2355 | 7288;7289;7290 | chr2:178773967;178773966;178773965 | chr2:179638694;179638693;179638692 |
| Novex-1 | 2355 | 7288;7289;7290 | chr2:178773967;178773966;178773965 | chr2:179638694;179638693;179638692 |
| Novex-2 | 2355 | 7288;7289;7290 | chr2:178773967;178773966;178773965 | chr2:179638694;179638693;179638692 |
| Novex-3 | 2401 | 7426;7427;7428 | chr2:178773967;178773966;178773965 | chr2:179638694;179638693;179638692 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | rs762102248  |
-1.498 | 0.864 | N | 0.768 | 0.4 | 0.671487266448 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/F | rs762102248 |
-1.498 | 0.864 | N | 0.768 | 0.4 | 0.671487266448 | gnomAD-4.0.0 | 3.18112E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86541E-05 | 0 |
| V/I | rs762102248 |
-0.76 | 0.006 | N | 0.244 | 0.067 | 0.344945010812 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| V/I | rs762102248 |
-0.76 | 0.006 | N | 0.244 | 0.067 | 0.344945010812 | gnomAD-4.0.0 | 4.77168E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.56991E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4449 | ambiguous | 0.4342 | ambiguous | -1.912 | Destabilizing | 0.645 | D | 0.473 | neutral | D | 0.555898762 | None | None | N |
| V/C | 0.7141 | likely_pathogenic | 0.6906 | pathogenic | -1.183 | Destabilizing | 0.995 | D | 0.753 | deleterious | None | None | None | None | N |
| V/D | 0.7881 | likely_pathogenic | 0.814 | pathogenic | -2.205 | Highly Destabilizing | 0.928 | D | 0.808 | deleterious | D | 0.583389887 | None | None | N |
| V/E | 0.6186 | likely_pathogenic | 0.6345 | pathogenic | -2.137 | Highly Destabilizing | 0.945 | D | 0.763 | deleterious | None | None | None | None | N |
| V/F | 0.1823 | likely_benign | 0.1788 | benign | -1.353 | Destabilizing | 0.864 | D | 0.768 | deleterious | N | 0.502374388 | None | None | N |
| V/G | 0.5006 | ambiguous | 0.5252 | ambiguous | -2.313 | Highly Destabilizing | 0.928 | D | 0.789 | deleterious | D | 0.581083999 | None | None | N |
| V/H | 0.7194 | likely_pathogenic | 0.7122 | pathogenic | -2.041 | Highly Destabilizing | 0.995 | D | 0.809 | deleterious | None | None | None | None | N |
| V/I | 0.0772 | likely_benign | 0.0742 | benign | -0.861 | Destabilizing | 0.006 | N | 0.244 | neutral | N | 0.451951631 | None | None | N |
| V/K | 0.6802 | likely_pathogenic | 0.6839 | pathogenic | -1.727 | Destabilizing | 0.945 | D | 0.768 | deleterious | None | None | None | None | N |
| V/L | 0.2724 | likely_benign | 0.2583 | benign | -0.861 | Destabilizing | 0.114 | N | 0.435 | neutral | N | 0.510177424 | None | None | N |
| V/M | 0.1833 | likely_benign | 0.1744 | benign | -0.565 | Destabilizing | 0.894 | D | 0.732 | prob.delet. | None | None | None | None | N |
| V/N | 0.5883 | likely_pathogenic | 0.5849 | pathogenic | -1.599 | Destabilizing | 0.981 | D | 0.821 | deleterious | None | None | None | None | N |
| V/P | 0.9749 | likely_pathogenic | 0.9789 | pathogenic | -1.18 | Destabilizing | 0.981 | D | 0.783 | deleterious | None | None | None | None | N |
| V/Q | 0.5942 | likely_pathogenic | 0.5954 | pathogenic | -1.676 | Destabilizing | 0.981 | D | 0.789 | deleterious | None | None | None | None | N |
| V/R | 0.6219 | likely_pathogenic | 0.6265 | pathogenic | -1.265 | Destabilizing | 0.945 | D | 0.821 | deleterious | None | None | None | None | N |
| V/S | 0.4986 | ambiguous | 0.4928 | ambiguous | -2.11 | Highly Destabilizing | 0.945 | D | 0.747 | deleterious | None | None | None | None | N |
| V/T | 0.3757 | ambiguous | 0.3546 | ambiguous | -1.934 | Destabilizing | 0.707 | D | 0.582 | neutral | None | None | None | None | N |
| V/W | 0.8551 | likely_pathogenic | 0.854 | pathogenic | -1.732 | Destabilizing | 0.995 | D | 0.776 | deleterious | None | None | None | None | N |
| V/Y | 0.5774 | likely_pathogenic | 0.5699 | pathogenic | -1.435 | Destabilizing | 0.945 | D | 0.771 | 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.