Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16600 | 50023;50024;50025 | chr2:178612923;178612922;178612921 | chr2:179477650;179477649;179477648 |
| N2AB | 14959 | 45100;45101;45102 | chr2:178612923;178612922;178612921 | chr2:179477650;179477649;179477648 |
| N2A | 14032 | 42319;42320;42321 | chr2:178612923;178612922;178612921 | chr2:179477650;179477649;179477648 |
| N2B | 7535 | 22828;22829;22830 | chr2:178612923;178612922;178612921 | chr2:179477650;179477649;179477648 |
| Novex-1 | 7660 | 23203;23204;23205 | chr2:178612923;178612922;178612921 | chr2:179477650;179477649;179477648 |
| Novex-2 | 7727 | 23404;23405;23406 | chr2:178612923;178612922;178612921 | chr2:179477650;179477649;179477648 |
| 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/T | rs762853490  |
-0.499 | 1.0 | N | 0.765 | 0.471 | 0.557050979708 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/T | rs762853490 |
-0.499 | 1.0 | N | 0.765 | 0.471 | 0.557050979708 | gnomAD-4.0.0 | 1.59351E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43332E-05 | 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 | 0.562 | ambiguous | 0.562 | ambiguous | -0.425 | Destabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | N |
| R/C | 0.2688 | likely_benign | 0.2376 | benign | -0.403 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| R/D | 0.877 | likely_pathogenic | 0.8876 | pathogenic | 0.087 | Stabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/E | 0.5856 | likely_pathogenic | 0.6157 | pathogenic | 0.215 | Stabilizing | 0.999 | D | 0.66 | neutral | None | None | None | None | N |
| R/F | 0.8098 | likely_pathogenic | 0.7977 | pathogenic | -0.203 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| R/G | 0.5777 | likely_pathogenic | 0.6049 | pathogenic | -0.739 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | N | 0.511148058 | None | None | N |
| R/H | 0.1961 | likely_benign | 0.1855 | benign | -1.111 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| R/I | 0.4384 | ambiguous | 0.4269 | ambiguous | 0.41 | Stabilizing | 1.0 | D | 0.783 | deleterious | N | 0.48265775 | None | None | N |
| R/K | 0.1511 | likely_benign | 0.1319 | benign | -0.468 | Destabilizing | 0.997 | D | 0.517 | neutral | N | 0.443067937 | None | None | N |
| R/L | 0.3856 | ambiguous | 0.3778 | ambiguous | 0.41 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/M | 0.4857 | ambiguous | 0.4793 | ambiguous | -0.07 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| R/N | 0.8067 | likely_pathogenic | 0.8025 | pathogenic | -0.03 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| R/P | 0.578 | likely_pathogenic | 0.5593 | ambiguous | 0.154 | Stabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| R/Q | 0.1687 | likely_benign | 0.1704 | benign | -0.117 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| R/S | 0.7233 | likely_pathogenic | 0.7326 | pathogenic | -0.659 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.477307171 | None | None | N |
| R/T | 0.3854 | ambiguous | 0.3949 | ambiguous | -0.349 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.465735861 | None | None | N |
| R/V | 0.4796 | ambiguous | 0.4478 | ambiguous | 0.154 | Stabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| R/W | 0.3864 | ambiguous | 0.4055 | ambiguous | 0.047 | Stabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| R/Y | 0.7176 | likely_pathogenic | 0.6996 | pathogenic | 0.35 | Stabilizing | 1.0 | D | 0.787 | 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.