Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9718 | 29377;29378;29379 | chr2:178706722;178706721;178706720 | chr2:179571449;179571448;179571447 |
| N2AB | 9401 | 28426;28427;28428 | chr2:178706722;178706721;178706720 | chr2:179571449;179571448;179571447 |
| N2A | 8474 | 25645;25646;25647 | chr2:178706722;178706721;178706720 | chr2:179571449;179571448;179571447 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/F | None | None | 0.994 | None | 0.593 | 0.328 | 0.524428966543 | gnomAD-4.0.0 | 6.86504E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.02094E-07 | 0 | 0 |
| I/S | rs4893852  |
-1.33 | 0.961 | None | 0.619 | 0.388 | 0.82519668701 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/S | rs4893852 |
-1.33 | 0.961 | None | 0.619 | 0.388 | 0.82519668701 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| I/S | rs4893852 |
-1.33 | 0.961 | None | 0.619 | 0.388 | 0.82519668701 | gnomAD-4.0.0 | 2.05126E-05 | None | None | None | None | I | None | 2.67938E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.4649E-05 | 0 | 3.21223E-05 |
| I/T | rs4893852 |
-1.165 | 0.4 | None | 0.423 | 0.216 | None | gnomAD-2.1.1 | 8.25144E-02 | None | None | None | None | I | None | 2.03964E-01 | 1.93592E-01 | None | 4.09357E-02 | 2.89833E-02 | None | 1.68648E-01 | None | 5.63403E-02 | 2.67532E-02 | 6.09997E-02 |
| I/T | rs4893852 |
-1.165 | 0.4 | None | 0.423 | 0.216 | None | gnomAD-3.1.2 | 9.38774E-02 | None | None | None | None | I | None | 2.01368E-01 | 1.51795E-01 | 4.27632E-02 | 3.60438E-02 | 2.61639E-02 | None | 5.75146E-02 | 5.37975E-02 | 2.60055E-02 | 1.60796E-01 | 7.53359E-02 |
| I/T | rs4893852 |
-1.165 | 0.4 | None | 0.423 | 0.216 | None | 1000 genomes | 1.27396E-01 | None | None | None | None | I | None | 2.231E-01 | 1.556E-01 | None | None | 2.58E-02 | 3.58E-02 | None | None | None | 1.769E-01 | None |
| I/T | rs4893852 |
-1.165 | 0.4 | None | 0.423 | 0.216 | None | gnomAD-4.0.0 | 5.01499E-02 | None | None | None | None | I | None | 2.04865E-01 | 1.81335E-01 | None | 3.95272E-02 | 1.50879E-02 | None | 5.8165E-02 | 4.82107E-02 | 2.61123E-02 | 1.59647E-01 | 5.62602E-02 |
| I/V | rs748067330 |
-0.89 | 0.817 | None | 0.411 | 0.193 | 0.610064410546 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 8.77E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs748067330 |
-0.89 | 0.817 | None | 0.411 | 0.193 | 0.610064410546 | gnomAD-4.0.0 | 2.74602E-06 | None | None | None | None | I | None | 0 | 6.75676E-05 | None | 0 | 0 | None | 1.87413E-05 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5268 | ambiguous | 0.3296 | benign | -2.064 | Highly Destabilizing | 0.964 | D | 0.564 | neutral | None | None | None | None | I |
| I/C | 0.8464 | likely_pathogenic | 0.7405 | pathogenic | -1.09 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | I |
| I/D | 0.9262 | likely_pathogenic | 0.8138 | pathogenic | -1.673 | Destabilizing | 0.998 | D | 0.703 | prob.neutral | None | None | None | None | I |
| I/E | 0.7778 | likely_pathogenic | 0.6312 | pathogenic | -1.634 | Destabilizing | 0.998 | D | 0.688 | prob.neutral | None | None | None | None | I |
| I/F | 0.1867 | likely_benign | 0.1311 | benign | -1.383 | Destabilizing | 0.994 | D | 0.593 | neutral | None | None | None | None | I |
| I/G | 0.9145 | likely_pathogenic | 0.7809 | pathogenic | -2.437 | Highly Destabilizing | 0.998 | D | 0.676 | prob.neutral | None | None | None | None | I |
| I/H | 0.6123 | likely_pathogenic | 0.4645 | ambiguous | -1.64 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| I/K | 0.5322 | ambiguous | 0.4044 | ambiguous | -1.504 | Destabilizing | 0.998 | D | 0.674 | neutral | None | None | None | None | I |
| I/L | 0.1584 | likely_benign | 0.1107 | benign | -1.075 | Destabilizing | 0.817 | D | 0.41 | neutral | None | None | None | None | I |
| I/M | 0.1471 | likely_benign | 0.1064 | benign | -0.734 | Destabilizing | 0.817 | D | 0.43 | neutral | None | None | None | None | I |
| I/N | 0.6087 | likely_pathogenic | 0.4184 | ambiguous | -1.302 | Destabilizing | 0.997 | D | 0.709 | prob.delet. | None | None | None | None | I |
| I/P | 0.9697 | likely_pathogenic | 0.9016 | pathogenic | -1.376 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | I |
| I/Q | 0.6225 | likely_pathogenic | 0.4671 | ambiguous | -1.458 | Destabilizing | 0.998 | D | 0.725 | prob.delet. | None | None | None | None | I |
| I/R | 0.406 | ambiguous | 0.2703 | benign | -0.872 | Destabilizing | 0.998 | D | 0.712 | prob.delet. | None | None | None | None | I |
| I/S | 0.5222 | ambiguous | 0.3342 | benign | -1.927 | Destabilizing | 0.961 | D | 0.619 | neutral | None | None | None | None | I |
| I/T | 0.214 | likely_benign | 0.116 | benign | -1.775 | Destabilizing | 0.4 | N | 0.423 | neutral | None | None | None | None | I |
| I/V | 0.1002 | likely_benign | 0.087 | benign | -1.376 | Destabilizing | 0.817 | D | 0.411 | neutral | None | None | None | None | I |
| I/W | 0.7731 | likely_pathogenic | 0.6653 | pathogenic | -1.512 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| I/Y | 0.6174 | likely_pathogenic | 0.5081 | ambiguous | -1.321 | Destabilizing | 0.999 | D | 0.678 | prob.neutral | None | None | None | None | I |
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.