Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31793 | 95602;95603;95604 | chr2:178545859;178545858;178545857 | chr2:179410586;179410585;179410584 |
| N2AB | 30152 | 90679;90680;90681 | chr2:178545859;178545858;178545857 | chr2:179410586;179410585;179410584 |
| N2A | 29225 | 87898;87899;87900 | chr2:178545859;178545858;178545857 | chr2:179410586;179410585;179410584 |
| N2B | 22728 | 68407;68408;68409 | chr2:178545859;178545858;178545857 | chr2:179410586;179410585;179410584 |
| Novex-1 | 22853 | 68782;68783;68784 | chr2:178545859;178545858;178545857 | chr2:179410586;179410585;179410584 |
| Novex-2 | 22920 | 68983;68984;68985 | chr2:178545859;178545858;178545857 | chr2:179410586;179410585;179410584 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | None | None | 0.996 | N | 0.563 | 0.404 | 0.326074293725 | gnomAD-4.0.0 | 1.36846E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.799E-06 | 0 | 0 |
| P/L | rs1696849077  |
None | 0.998 | D | 0.733 | 0.476 | 0.617224619168 | gnomAD-4.0.0 | 1.44039E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.575E-05 | 0 | 0 |
| P/T | rs1466581888 |
-1.591 | 0.999 | N | 0.703 | 0.386 | 0.411799315854 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/T | rs1466581888 |
-1.591 | 0.999 | N | 0.703 | 0.386 | 0.411799315854 | gnomAD-4.0.0 | 3.42116E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.79764E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0615 | likely_benign | 0.0667 | benign | -1.404 | Destabilizing | 0.996 | D | 0.563 | neutral | N | 0.49434443 | None | None | N |
| P/C | 0.4279 | ambiguous | 0.4327 | ambiguous | -0.815 | Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| P/D | 0.7719 | likely_pathogenic | 0.8117 | pathogenic | -1.328 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| P/E | 0.6152 | likely_pathogenic | 0.6816 | pathogenic | -1.375 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | N |
| P/F | 0.4897 | ambiguous | 0.4513 | ambiguous | -1.158 | Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| P/G | 0.3348 | likely_benign | 0.3423 | ambiguous | -1.663 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| P/H | 0.4107 | ambiguous | 0.4086 | ambiguous | -1.155 | Destabilizing | 1.0 | D | 0.807 | deleterious | N | 0.514476602 | None | None | N |
| P/I | 0.4435 | ambiguous | 0.5159 | ambiguous | -0.808 | Destabilizing | 0.998 | D | 0.739 | prob.delet. | None | None | None | None | N |
| P/K | 0.7908 | likely_pathogenic | 0.8399 | pathogenic | -1.259 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| P/L | 0.2731 | likely_benign | 0.3041 | benign | -0.808 | Destabilizing | 0.998 | D | 0.733 | prob.delet. | D | 0.523298012 | None | None | N |
| P/M | 0.4232 | ambiguous | 0.473 | ambiguous | -0.577 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| P/N | 0.615 | likely_pathogenic | 0.6442 | pathogenic | -0.911 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| P/Q | 0.4475 | ambiguous | 0.4886 | ambiguous | -1.162 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| P/R | 0.6429 | likely_pathogenic | 0.6986 | pathogenic | -0.615 | Destabilizing | 1.0 | D | 0.784 | deleterious | D | 0.531566899 | None | None | N |
| P/S | 0.1499 | likely_benign | 0.1588 | benign | -1.333 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | N | 0.512955665 | None | None | N |
| P/T | 0.1696 | likely_benign | 0.2073 | benign | -1.289 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | N | 0.513716133 | None | None | N |
| P/V | 0.2721 | likely_benign | 0.3254 | benign | -0.973 | Destabilizing | 0.91 | D | 0.48 | neutral | None | None | None | None | N |
| P/W | 0.6898 | likely_pathogenic | 0.6742 | pathogenic | -1.273 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| P/Y | 0.5493 | ambiguous | 0.5178 | ambiguous | -1.044 | Destabilizing | 1.0 | D | 0.82 | 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.