Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16769 | 50530;50531;50532 | chr2:178612106;178612105;178612104 | chr2:179476833;179476832;179476831 |
| N2AB | 15128 | 45607;45608;45609 | chr2:178612106;178612105;178612104 | chr2:179476833;179476832;179476831 |
| N2A | 14201 | 42826;42827;42828 | chr2:178612106;178612105;178612104 | chr2:179476833;179476832;179476831 |
| N2B | 7704 | 23335;23336;23337 | chr2:178612106;178612105;178612104 | chr2:179476833;179476832;179476831 |
| Novex-1 | 7829 | 23710;23711;23712 | chr2:178612106;178612105;178612104 | chr2:179476833;179476832;179476831 |
| Novex-2 | 7896 | 23911;23912;23913 | chr2:178612106;178612105;178612104 | chr2:179476833;179476832;179476831 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs757648293  |
-0.869 | 0.046 | N | 0.399 | 0.114 | 0.202949470691 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| D/E | rs757648293 |
-0.869 | 0.046 | N | 0.399 | 0.114 | 0.202949470691 | gnomAD-4.0.0 | 2.05495E-06 | None | None | None | None | N | None | 2.99437E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80012E-06 | 0 | 0 |
| D/G | rs1233925811 |
-1.21 | 0.046 | N | 0.414 | 0.287 | 0.204665344411 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| D/N | None | None | 0.982 | N | 0.587 | 0.3 | 0.325263233342 | gnomAD-4.0.0 | 4.10997E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.40043E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.5902 | likely_pathogenic | 0.6392 | pathogenic | -0.745 | Destabilizing | 0.939 | D | 0.679 | prob.neutral | N | 0.474949158 | None | None | N |
| D/C | 0.9307 | likely_pathogenic | 0.9326 | pathogenic | -0.665 | Destabilizing | 0.999 | D | 0.811 | deleterious | None | None | None | None | N |
| D/E | 0.4328 | ambiguous | 0.4644 | ambiguous | -0.965 | Destabilizing | 0.046 | N | 0.399 | neutral | N | 0.456614856 | None | None | N |
| D/F | 0.8407 | likely_pathogenic | 0.8704 | pathogenic | -0.756 | Destabilizing | 0.999 | D | 0.845 | deleterious | None | None | None | None | N |
| D/G | 0.74 | likely_pathogenic | 0.7737 | pathogenic | -1.11 | Destabilizing | 0.046 | N | 0.414 | neutral | N | 0.464984195 | None | None | N |
| D/H | 0.6747 | likely_pathogenic | 0.706 | pathogenic | -1.189 | Destabilizing | 0.998 | D | 0.755 | deleterious | N | 0.475714829 | None | None | N |
| D/I | 0.6463 | likely_pathogenic | 0.7323 | pathogenic | 0.238 | Stabilizing | 0.993 | D | 0.863 | deleterious | None | None | None | None | N |
| D/K | 0.8737 | likely_pathogenic | 0.9126 | pathogenic | -1.392 | Destabilizing | 0.973 | D | 0.71 | prob.delet. | None | None | None | None | N |
| D/L | 0.6614 | likely_pathogenic | 0.754 | pathogenic | 0.238 | Stabilizing | 0.986 | D | 0.825 | deleterious | None | None | None | None | N |
| D/M | 0.8697 | likely_pathogenic | 0.8986 | pathogenic | 0.791 | Stabilizing | 0.999 | D | 0.83 | deleterious | None | None | None | None | N |
| D/N | 0.2732 | likely_benign | 0.2768 | benign | -1.54 | Destabilizing | 0.982 | D | 0.587 | neutral | N | 0.470538038 | None | None | N |
| D/P | 0.9931 | likely_pathogenic | 0.9937 | pathogenic | -0.066 | Destabilizing | 0.993 | D | 0.747 | deleterious | None | None | None | None | N |
| D/Q | 0.7824 | likely_pathogenic | 0.819 | pathogenic | -1.279 | Destabilizing | 0.973 | D | 0.676 | prob.neutral | None | None | None | None | N |
| D/R | 0.8902 | likely_pathogenic | 0.9168 | pathogenic | -1.357 | Destabilizing | 0.986 | D | 0.778 | deleterious | None | None | None | None | N |
| D/S | 0.4145 | ambiguous | 0.4227 | ambiguous | -2.007 | Highly Destabilizing | 0.953 | D | 0.554 | neutral | None | None | None | None | N |
| D/T | 0.5845 | likely_pathogenic | 0.6089 | pathogenic | -1.699 | Destabilizing | 0.986 | D | 0.708 | prob.delet. | None | None | None | None | N |
| D/V | 0.4631 | ambiguous | 0.5487 | ambiguous | -0.066 | Destabilizing | 0.991 | D | 0.824 | deleterious | N | 0.439631468 | None | None | N |
| D/W | 0.9779 | likely_pathogenic | 0.9809 | pathogenic | -0.952 | Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | N |
| D/Y | 0.5599 | ambiguous | 0.6316 | pathogenic | -0.665 | Destabilizing | 0.999 | D | 0.846 | deleterious | N | 0.464501979 | 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.