Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23049 | 69370;69371;69372 | chr2:178577190;178577189;178577188 | chr2:179441917;179441916;179441915 |
| N2AB | 21408 | 64447;64448;64449 | chr2:178577190;178577189;178577188 | chr2:179441917;179441916;179441915 |
| N2A | 20481 | 61666;61667;61668 | chr2:178577190;178577189;178577188 | chr2:179441917;179441916;179441915 |
| N2B | 13984 | 42175;42176;42177 | chr2:178577190;178577189;178577188 | chr2:179441917;179441916;179441915 |
| Novex-1 | 14109 | 42550;42551;42552 | chr2:178577190;178577189;178577188 | chr2:179441917;179441916;179441915 |
| Novex-2 | 14176 | 42751;42752;42753 | chr2:178577190;178577189;178577188 | chr2:179441917;179441916;179441915 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | None | None | 0.183 | N | 0.453 | 0.176 | 0.543428762037 | gnomAD-4.0.0 | 4.77841E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.58119E-06 | 0 | 0 |
| I/V | rs72646881  |
-0.872 | None | N | 0.118 | 0.09 | None | gnomAD-2.1.1 | 1.11649E-02 | None | None | None | None | N | None | 1.1307E-01 | 5.5606E-03 | None | 5.52647E-03 | 0 | None | 2.94272E-04 | None | 0 | 6.9896E-04 | 4.37853E-03 |
| I/V | rs72646881 |
-0.872 | None | N | 0.118 | 0.09 | None | gnomAD-3.1.2 | 3.27723E-02 | None | None | None | None | N | None | 1.12899E-01 | 1.2999E-02 | 0 | 6.62824E-03 | 1.94175E-04 | None | 0 | 6.32911E-03 | 5.88582E-04 | 2.08073E-04 | 2.15517E-02 |
| I/V | rs72646881 |
-0.872 | None | N | 0.118 | 0.09 | None | 1000 genomes | 3.63419E-02 | None | None | None | None | N | None | 1.278E-01 | 1.73E-02 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| I/V | rs72646881 |
-0.872 | None | N | 0.118 | 0.09 | None | gnomAD-4.0.0 | 6.56266E-03 | None | None | None | None | N | None | 1.15739E-01 | 7.82397E-03 | None | 6.92802E-03 | 2.24024E-05 | None | 1.56377E-05 | 6.44628E-03 | 5.35845E-04 | 2.5262E-04 | 8.72978E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4842 | ambiguous | 0.4904 | ambiguous | -1.668 | Destabilizing | 0.001 | N | 0.275 | neutral | None | None | None | None | N |
| I/C | 0.6937 | likely_pathogenic | 0.7171 | pathogenic | -1.353 | Destabilizing | 0.836 | D | 0.575 | neutral | None | None | None | None | N |
| I/D | 0.9481 | likely_pathogenic | 0.9501 | pathogenic | -0.559 | Destabilizing | 0.593 | D | 0.684 | prob.neutral | None | None | None | None | N |
| I/E | 0.9293 | likely_pathogenic | 0.9253 | pathogenic | -0.517 | Destabilizing | 0.593 | D | 0.617 | neutral | None | None | None | None | N |
| I/F | 0.21 | likely_benign | 0.1981 | benign | -1.119 | Destabilizing | 0.002 | N | 0.241 | neutral | N | 0.481557996 | None | None | N |
| I/G | 0.835 | likely_pathogenic | 0.8457 | pathogenic | -2.027 | Highly Destabilizing | 0.129 | N | 0.52 | neutral | None | None | None | None | N |
| I/H | 0.862 | likely_pathogenic | 0.8601 | pathogenic | -1.247 | Destabilizing | 0.94 | D | 0.627 | neutral | None | None | None | None | N |
| I/K | 0.8525 | likely_pathogenic | 0.8278 | pathogenic | -1.061 | Destabilizing | 0.418 | N | 0.604 | neutral | None | None | None | None | N |
| I/L | 0.1878 | likely_benign | 0.1969 | benign | -0.745 | Destabilizing | 0.001 | N | 0.128 | neutral | N | 0.495276655 | None | None | N |
| I/M | 0.1742 | likely_benign | 0.1736 | benign | -0.768 | Destabilizing | 0.655 | D | 0.545 | neutral | N | 0.489779436 | None | None | N |
| I/N | 0.6741 | likely_pathogenic | 0.6777 | pathogenic | -0.932 | Destabilizing | 0.921 | D | 0.666 | neutral | N | 0.508644159 | None | None | N |
| I/P | 0.7896 | likely_pathogenic | 0.7734 | pathogenic | -1.022 | Destabilizing | 0.836 | D | 0.677 | prob.neutral | None | None | None | None | N |
| I/Q | 0.8641 | likely_pathogenic | 0.8607 | pathogenic | -1.007 | Destabilizing | 0.94 | D | 0.648 | neutral | None | None | None | None | N |
| I/R | 0.8175 | likely_pathogenic | 0.7869 | pathogenic | -0.631 | Destabilizing | 0.836 | D | 0.68 | prob.neutral | None | None | None | None | N |
| I/S | 0.5951 | likely_pathogenic | 0.6117 | pathogenic | -1.693 | Destabilizing | 0.101 | N | 0.463 | neutral | N | 0.49274195 | None | None | N |
| I/T | 0.4608 | ambiguous | 0.4525 | ambiguous | -1.511 | Destabilizing | 0.183 | N | 0.453 | neutral | N | 0.470282829 | None | None | N |
| I/V | 0.0832 | likely_benign | 0.0857 | benign | -1.022 | Destabilizing | None | N | 0.118 | neutral | N | 0.384508665 | None | None | N |
| I/W | 0.8932 | likely_pathogenic | 0.8896 | pathogenic | -1.151 | Destabilizing | 0.983 | D | 0.618 | neutral | None | None | None | None | N |
| I/Y | 0.6749 | likely_pathogenic | 0.664 | pathogenic | -0.924 | Destabilizing | 0.264 | N | 0.591 | neutral | 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.