Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31250 | 93973;93974;93975 | chr2:178547878;178547877;178547876 | chr2:179412605;179412604;179412603 |
| N2AB | 29609 | 89050;89051;89052 | chr2:178547878;178547877;178547876 | chr2:179412605;179412604;179412603 |
| N2A | 28682 | 86269;86270;86271 | chr2:178547878;178547877;178547876 | chr2:179412605;179412604;179412603 |
| N2B | 22185 | 66778;66779;66780 | chr2:178547878;178547877;178547876 | chr2:179412605;179412604;179412603 |
| Novex-1 | 22310 | 67153;67154;67155 | chr2:178547878;178547877;178547876 | chr2:179412605;179412604;179412603 |
| Novex-2 | 22377 | 67354;67355;67356 | chr2:178547878;178547877;178547876 | chr2:179412605;179412604;179412603 |
| 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 | rs1559163775  |
None | 0.996 | N | 0.487 | 0.351 | 0.214338557667 | gnomAD-4.0.0 | 3.18225E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77423E-05 | None | 0 | 0 | 0 | 1.43271E-05 | 0 |
| K/Q | None | None | 0.999 | N | 0.692 | 0.302 | 0.187945064343 | gnomAD-4.0.0 | 4.77338E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71576E-06 | 1.43271E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.6603 | likely_pathogenic | 0.7391 | pathogenic | -1.266 | Destabilizing | 0.998 | D | 0.557 | neutral | None | None | None | None | N |
| K/C | 0.7605 | likely_pathogenic | 0.8056 | pathogenic | -1.365 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| K/D | 0.8779 | likely_pathogenic | 0.9139 | pathogenic | -1.125 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| K/E | 0.4425 | ambiguous | 0.5456 | ambiguous | -0.878 | Destabilizing | 0.996 | D | 0.487 | neutral | N | 0.507656015 | None | None | N |
| K/F | 0.7939 | likely_pathogenic | 0.8487 | pathogenic | -0.564 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| K/G | 0.7797 | likely_pathogenic | 0.8438 | pathogenic | -1.723 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| K/H | 0.3655 | ambiguous | 0.4196 | ambiguous | -1.809 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| K/I | 0.4663 | ambiguous | 0.544 | ambiguous | 0.001 | Stabilizing | 1.0 | D | 0.803 | deleterious | N | 0.485952591 | None | None | N |
| K/L | 0.3852 | ambiguous | 0.4525 | ambiguous | 0.001 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| K/M | 0.244 | likely_benign | 0.2854 | benign | -0.319 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| K/N | 0.6973 | likely_pathogenic | 0.7711 | pathogenic | -1.396 | Destabilizing | 0.999 | D | 0.696 | prob.neutral | N | 0.465149089 | None | None | N |
| K/P | 0.9893 | likely_pathogenic | 0.9927 | pathogenic | -0.397 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| K/Q | 0.1761 | likely_benign | 0.2253 | benign | -1.192 | Destabilizing | 0.999 | D | 0.692 | prob.neutral | N | 0.45312122 | None | None | N |
| K/R | 0.1024 | likely_benign | 0.1173 | benign | -0.994 | Destabilizing | 0.884 | D | 0.273 | neutral | N | 0.490878408 | None | None | N |
| K/S | 0.6913 | likely_pathogenic | 0.7689 | pathogenic | -2.047 | Highly Destabilizing | 0.998 | D | 0.548 | neutral | None | None | None | None | N |
| K/T | 0.3269 | likely_benign | 0.3884 | ambiguous | -1.553 | Destabilizing | 0.999 | D | 0.724 | prob.delet. | N | 0.43290754 | None | None | N |
| K/V | 0.4345 | ambiguous | 0.5037 | ambiguous | -0.397 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| K/W | 0.811 | likely_pathogenic | 0.8574 | pathogenic | -0.512 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| K/Y | 0.6504 | likely_pathogenic | 0.7006 | pathogenic | -0.181 | Destabilizing | 1.0 | D | 0.796 | 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.