Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24563 | 73912;73913;73914 | chr2:178572445;178572444;178572443 | chr2:179437172;179437171;179437170 |
| N2AB | 22922 | 68989;68990;68991 | chr2:178572445;178572444;178572443 | chr2:179437172;179437171;179437170 |
| N2A | 21995 | 66208;66209;66210 | chr2:178572445;178572444;178572443 | chr2:179437172;179437171;179437170 |
| N2B | 15498 | 46717;46718;46719 | chr2:178572445;178572444;178572443 | chr2:179437172;179437171;179437170 |
| Novex-1 | 15623 | 47092;47093;47094 | chr2:178572445;178572444;178572443 | chr2:179437172;179437171;179437170 |
| Novex-2 | 15690 | 47293;47294;47295 | chr2:178572445;178572444;178572443 | chr2:179437172;179437171;179437170 |
| 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 | 0.021 | N | 0.343 | 0.223 | 0.285316908763 | gnomAD-4.0.0 | 1.59418E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86525E-06 | 0 | 0 |
| R/T | rs560347347  |
-0.213 | 0.98 | N | 0.346 | 0.381 | 0.38242337071 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93723E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs560347347 |
-0.213 | 0.98 | N | 0.346 | 0.381 | 0.38242337071 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/T | rs560347347 |
-0.213 | 0.98 | N | 0.346 | 0.381 | 0.38242337071 | gnomAD-4.0.0 | 6.57091E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.94175E-04 | None | 0 | 0 | 0 | 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 | 0.9911 | likely_pathogenic | 0.9819 | pathogenic | -0.544 | Destabilizing | 0.823 | D | 0.421 | neutral | None | None | None | None | N |
| R/C | 0.9189 | likely_pathogenic | 0.8223 | pathogenic | -0.494 | Destabilizing | 0.999 | D | 0.611 | neutral | None | None | None | None | N |
| R/D | 0.9985 | likely_pathogenic | 0.9969 | pathogenic | -0.048 | Destabilizing | 0.97 | D | 0.411 | neutral | None | None | None | None | N |
| R/E | 0.9891 | likely_pathogenic | 0.9784 | pathogenic | 0.021 | Stabilizing | 0.85 | D | 0.307 | neutral | None | None | None | None | N |
| R/F | 0.9929 | likely_pathogenic | 0.9835 | pathogenic | -0.697 | Destabilizing | 0.988 | D | 0.537 | neutral | None | None | None | None | N |
| R/G | 0.9757 | likely_pathogenic | 0.9447 | pathogenic | -0.772 | Destabilizing | 0.021 | N | 0.343 | neutral | N | 0.504874786 | None | None | N |
| R/H | 0.8351 | likely_pathogenic | 0.6416 | pathogenic | -1.115 | Destabilizing | 0.988 | D | 0.303 | neutral | None | None | None | None | N |
| R/I | 0.989 | likely_pathogenic | 0.9768 | pathogenic | 0.036 | Stabilizing | 0.984 | D | 0.544 | neutral | N | 0.504134254 | None | None | N |
| R/K | 0.6173 | likely_pathogenic | 0.4955 | ambiguous | -0.531 | Destabilizing | 0.257 | N | 0.371 | neutral | N | 0.462644162 | None | None | N |
| R/L | 0.9556 | likely_pathogenic | 0.9197 | pathogenic | 0.036 | Stabilizing | 0.965 | D | 0.365 | neutral | None | None | None | None | N |
| R/M | 0.9766 | likely_pathogenic | 0.9477 | pathogenic | -0.161 | Destabilizing | 0.997 | D | 0.377 | neutral | None | None | None | None | N |
| R/N | 0.9966 | likely_pathogenic | 0.9924 | pathogenic | 0.005 | Stabilizing | 0.97 | D | 0.317 | neutral | None | None | None | None | N |
| R/P | 0.9986 | likely_pathogenic | 0.9968 | pathogenic | -0.137 | Destabilizing | 0.995 | D | 0.446 | neutral | None | None | None | None | N |
| R/Q | 0.7858 | likely_pathogenic | 0.6196 | pathogenic | -0.256 | Destabilizing | 0.993 | D | 0.347 | neutral | None | None | None | None | N |
| R/S | 0.995 | likely_pathogenic | 0.9892 | pathogenic | -0.651 | Destabilizing | 0.875 | D | 0.38 | neutral | N | 0.477034824 | None | None | N |
| R/T | 0.9934 | likely_pathogenic | 0.9839 | pathogenic | -0.437 | Destabilizing | 0.98 | D | 0.346 | neutral | N | 0.492716353 | None | None | N |
| R/V | 0.9887 | likely_pathogenic | 0.9777 | pathogenic | -0.137 | Destabilizing | 0.952 | D | 0.54 | neutral | None | None | None | None | N |
| R/W | 0.9144 | likely_pathogenic | 0.7905 | pathogenic | -0.508 | Destabilizing | 0.999 | D | 0.644 | neutral | None | None | None | None | N |
| R/Y | 0.9793 | likely_pathogenic | 0.9531 | pathogenic | -0.158 | Destabilizing | 0.988 | D | 0.449 | neutral | 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.