Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26648 | 80167;80168;80169 | chr2:178566190;178566189;178566188 | chr2:179430917;179430916;179430915 |
| N2AB | 25007 | 75244;75245;75246 | chr2:178566190;178566189;178566188 | chr2:179430917;179430916;179430915 |
| N2A | 24080 | 72463;72464;72465 | chr2:178566190;178566189;178566188 | chr2:179430917;179430916;179430915 |
| N2B | 17583 | 52972;52973;52974 | chr2:178566190;178566189;178566188 | chr2:179430917;179430916;179430915 |
| Novex-1 | 17708 | 53347;53348;53349 | chr2:178566190;178566189;178566188 | chr2:179430917;179430916;179430915 |
| Novex-2 | 17775 | 53548;53549;53550 | chr2:178566190;178566189;178566188 | chr2:179430917;179430916;179430915 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/I | None | None | 0.884 | D | 0.445 | 0.421 | 0.586357277508 | gnomAD-4.0.0 | 1.5915E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85878E-06 | 0 | 0 |
| L/Q | rs1302262085  |
-2.206 | 1.0 | D | 0.863 | 0.82 | 0.837580165448 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| L/Q | rs1302262085 |
-2.206 | 1.0 | D | 0.863 | 0.82 | 0.837580165448 | gnomAD-4.0.0 | 6.84251E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99526E-07 | 0 | 0 |
| L/R | None | None | 1.0 | D | 0.86 | 0.825 | 0.808672001573 | gnomAD-4.0.0 | 1.3685E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79905E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9359 | likely_pathogenic | 0.9297 | pathogenic | -2.547 | Highly Destabilizing | 0.998 | D | 0.69 | prob.neutral | None | None | None | None | N |
| L/C | 0.8679 | likely_pathogenic | 0.8635 | pathogenic | -2.003 | Highly Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| L/D | 0.9996 | likely_pathogenic | 0.9994 | pathogenic | -3.371 | Highly Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| L/E | 0.9973 | likely_pathogenic | 0.9961 | pathogenic | -3.039 | Highly Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| L/F | 0.4308 | ambiguous | 0.4082 | ambiguous | -1.548 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| L/G | 0.991 | likely_pathogenic | 0.9899 | pathogenic | -3.167 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| L/H | 0.9877 | likely_pathogenic | 0.9819 | pathogenic | -2.992 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| L/I | 0.1664 | likely_benign | 0.1472 | benign | -0.682 | Destabilizing | 0.884 | D | 0.445 | neutral | D | 0.526609598 | None | None | N |
| L/K | 0.9932 | likely_pathogenic | 0.9903 | pathogenic | -2.042 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| L/M | 0.2563 | likely_benign | 0.2519 | benign | -0.967 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| L/N | 0.9972 | likely_pathogenic | 0.9962 | pathogenic | -2.792 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| L/P | 0.9981 | likely_pathogenic | 0.9972 | pathogenic | -1.295 | Destabilizing | 1.0 | D | 0.878 | deleterious | D | 0.574089189 | None | None | N |
| L/Q | 0.9863 | likely_pathogenic | 0.9805 | pathogenic | -2.396 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | D | 0.574089189 | None | None | N |
| L/R | 0.9869 | likely_pathogenic | 0.9817 | pathogenic | -2.226 | Highly Destabilizing | 1.0 | D | 0.86 | deleterious | D | 0.574089189 | None | None | N |
| L/S | 0.9949 | likely_pathogenic | 0.9933 | pathogenic | -3.337 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| L/T | 0.9807 | likely_pathogenic | 0.9755 | pathogenic | -2.827 | Highly Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| L/V | 0.2139 | likely_benign | 0.2044 | benign | -1.295 | Destabilizing | 0.981 | D | 0.709 | prob.delet. | D | 0.534460411 | None | None | N |
| L/W | 0.9269 | likely_pathogenic | 0.9026 | pathogenic | -1.948 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| L/Y | 0.9068 | likely_pathogenic | 0.8907 | pathogenic | -1.716 | Destabilizing | 1.0 | D | 0.784 | 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.