Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32937 | 99034;99035;99036 | chr2:178539126;178539125;178539124 | chr2:179403853;179403852;179403851 |
| N2AB | 31296 | 94111;94112;94113 | chr2:178539126;178539125;178539124 | chr2:179403853;179403852;179403851 |
| N2A | 30369 | 91330;91331;91332 | chr2:178539126;178539125;178539124 | chr2:179403853;179403852;179403851 |
| N2B | 23872 | 71839;71840;71841 | chr2:178539126;178539125;178539124 | chr2:179403853;179403852;179403851 |
| Novex-1 | 23997 | 72214;72215;72216 | chr2:178539126;178539125;178539124 | chr2:179403853;179403852;179403851 |
| Novex-2 | 24064 | 72415;72416;72417 | chr2:178539126;178539125;178539124 | chr2:179403853;179403852;179403851 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs200544701  |
-0.841 | 0.722 | N | 0.512 | 0.167 | None | gnomAD-2.1.1 | 1.96287E-04 | None | None | None | None | N | None | 0 | 5.09251E-04 | None | 2.90135E-03 | 0 | None | 6.54E-05 | None | 0 | 1.56E-05 | 4.20994E-04 |
| K/E | rs200544701 |
-0.841 | 0.722 | N | 0.512 | 0.167 | None | gnomAD-3.1.2 | 1.05169E-04 | None | None | None | None | N | None | 0 | 2.62089E-04 | 0 | 2.59366E-03 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| K/E | rs200544701 |
-0.841 | 0.722 | N | 0.512 | 0.167 | None | gnomAD-4.0.0 | 9.17171E-05 | None | None | None | None | N | None | 1.33501E-05 | 4.66838E-04 | None | 2.80424E-03 | 0 | None | 0 | 0 | 2.11908E-05 | 2.19573E-05 | 1.44106E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.9448 | likely_pathogenic | 0.9115 | pathogenic | -1.325 | Destabilizing | 0.775 | D | 0.602 | neutral | None | None | None | None | N |
| K/C | 0.8814 | likely_pathogenic | 0.8044 | pathogenic | -1.514 | Destabilizing | 0.996 | D | 0.803 | deleterious | None | None | None | None | N |
| K/D | 0.9949 | likely_pathogenic | 0.9929 | pathogenic | -1.867 | Destabilizing | 0.923 | D | 0.681 | prob.neutral | None | None | None | None | N |
| K/E | 0.8538 | likely_pathogenic | 0.7995 | pathogenic | -1.62 | Destabilizing | 0.722 | D | 0.512 | neutral | N | 0.479539199 | None | None | N |
| K/F | 0.9775 | likely_pathogenic | 0.9618 | pathogenic | -0.735 | Destabilizing | 0.987 | D | 0.797 | deleterious | None | None | None | None | N |
| K/G | 0.963 | likely_pathogenic | 0.9489 | pathogenic | -1.748 | Destabilizing | 0.775 | D | 0.672 | neutral | None | None | None | None | N |
| K/H | 0.7526 | likely_pathogenic | 0.7025 | pathogenic | -2.051 | Highly Destabilizing | 0.961 | D | 0.731 | prob.delet. | None | None | None | None | N |
| K/I | 0.9059 | likely_pathogenic | 0.8414 | pathogenic | -0.147 | Destabilizing | 0.949 | D | 0.803 | deleterious | D | 0.52429284 | None | None | N |
| K/L | 0.802 | likely_pathogenic | 0.6972 | pathogenic | -0.147 | Destabilizing | 0.775 | D | 0.672 | neutral | None | None | None | None | N |
| K/M | 0.6551 | likely_pathogenic | 0.5371 | ambiguous | -0.523 | Destabilizing | 0.996 | D | 0.714 | prob.delet. | None | None | None | None | N |
| K/N | 0.9703 | likely_pathogenic | 0.9592 | pathogenic | -1.686 | Destabilizing | 0.722 | D | 0.519 | neutral | N | 0.516750792 | None | None | N |
| K/P | 0.9985 | likely_pathogenic | 0.998 | pathogenic | -0.518 | Destabilizing | 0.987 | D | 0.721 | prob.delet. | None | None | None | None | N |
| K/Q | 0.3847 | ambiguous | 0.2912 | benign | -1.403 | Destabilizing | 0.722 | D | 0.527 | neutral | N | 0.429283736 | None | None | N |
| K/R | 0.0873 | likely_benign | 0.0823 | benign | -1.234 | Destabilizing | 0.003 | N | 0.125 | neutral | N | 0.385935604 | None | None | N |
| K/S | 0.9728 | likely_pathogenic | 0.9604 | pathogenic | -2.135 | Highly Destabilizing | 0.775 | D | 0.469 | neutral | None | None | None | None | N |
| K/T | 0.9021 | likely_pathogenic | 0.87 | pathogenic | -1.665 | Destabilizing | 0.722 | D | 0.629 | neutral | N | 0.51038218 | None | None | N |
| K/V | 0.8843 | likely_pathogenic | 0.821 | pathogenic | -0.518 | Destabilizing | 0.961 | D | 0.707 | prob.neutral | None | None | None | None | N |
| K/W | 0.9579 | likely_pathogenic | 0.9395 | pathogenic | -0.903 | Destabilizing | 0.996 | D | 0.773 | deleterious | None | None | None | None | N |
| K/Y | 0.9289 | likely_pathogenic | 0.8962 | pathogenic | -0.499 | Destabilizing | 0.987 | D | 0.785 | 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.