Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4995 | 15208;15209;15210 | chr2:178734941;178734940;178734939 | chr2:179599668;179599667;179599666 |
| N2AB | 4678 | 14257;14258;14259 | chr2:178734941;178734940;178734939 | chr2:179599668;179599667;179599666 |
| N2A | 3751 | 11476;11477;11478 | chr2:178734941;178734940;178734939 | chr2:179599668;179599667;179599666 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/R | rs72648927  |
-0.217 | 0.669 | N | 0.381 | 0.189 | None | gnomAD-2.1.1 | 8.09052E-03 | None | None | None | None | I | None | 1.4457E-03 | 2.09774E-03 | None | 1.07665E-02 | 0 | None | 5.13975E-03 | None | 2.47396E-02 | 9.38074E-03 | 8.53341E-03 |
| P/R | rs72648927 |
-0.217 | 0.669 | N | 0.381 | 0.189 | None | gnomAD-3.1.2 | 7.18952E-03 | None | None | None | None | I | None | 1.27927E-03 | 2.09561E-03 | 0 | 1.00865E-02 | 0 | None | 2.64545E-02 | 0 | 9.64309E-03 | 4.1425E-03 | 8.12619E-03 |
| P/R | rs72648927 |
-0.217 | 0.669 | N | 0.381 | 0.189 | None | 1000 genomes | 4.39297E-03 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 1.89E-02 | None | None | None | 2E-03 | None |
| P/R | rs72648927 |
-0.217 | 0.669 | N | 0.381 | 0.189 | None | gnomAD-4.0.0 | 8.84273E-03 | None | None | None | None | I | None | 1.29406E-03 | 2.28891E-03 | None | 1.09845E-02 | 0 | None | 2.53194E-02 | 2.31482E-03 | 9.40517E-03 | 4.92611E-03 | 8.42724E-03 |
| P/S | rs776578141 |
-0.91 | 0.801 | N | 0.293 | 0.203 | 0.132336055621 | gnomAD-2.1.1 | 1.27E-05 | None | None | None | None | I | None | 6.77E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.5E-06 | 1.72295E-04 |
| P/S | rs776578141 |
-0.91 | 0.801 | N | 0.293 | 0.203 | 0.132336055621 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs776578141 |
-0.91 | 0.801 | N | 0.293 | 0.203 | 0.132336055621 | gnomAD-4.0.0 | 2.23889E-05 | None | None | None | None | I | None | 1.33683E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8894E-05 | 0 | 1.6057E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.125 | likely_benign | 0.1358 | benign | -0.968 | Destabilizing | 0.625 | D | 0.283 | neutral | N | 0.406292338 | None | None | I |
| P/C | 0.744 | likely_pathogenic | 0.7751 | pathogenic | -0.83 | Destabilizing | 0.998 | D | 0.404 | neutral | None | None | None | None | I |
| P/D | 0.8294 | likely_pathogenic | 0.8395 | pathogenic | -0.634 | Destabilizing | 0.842 | D | 0.325 | neutral | None | None | None | None | I |
| P/E | 0.4227 | ambiguous | 0.4338 | ambiguous | -0.689 | Destabilizing | 0.728 | D | 0.279 | neutral | None | None | None | None | I |
| P/F | 0.8039 | likely_pathogenic | 0.7955 | pathogenic | -0.811 | Destabilizing | 0.949 | D | 0.397 | neutral | None | None | None | None | I |
| P/G | 0.6193 | likely_pathogenic | 0.6598 | pathogenic | -1.201 | Destabilizing | 0.915 | D | 0.361 | neutral | None | None | None | None | I |
| P/H | 0.399 | ambiguous | 0.3886 | ambiguous | -0.633 | Destabilizing | 0.974 | D | 0.368 | neutral | None | None | None | None | I |
| P/I | 0.4801 | ambiguous | 0.4778 | ambiguous | -0.467 | Destabilizing | 0.904 | D | 0.391 | neutral | None | None | None | None | I |
| P/K | 0.4457 | ambiguous | 0.4917 | ambiguous | -0.898 | Destabilizing | 0.067 | N | 0.202 | neutral | None | None | None | None | I |
| P/L | 0.1804 | likely_benign | 0.1865 | benign | -0.467 | Destabilizing | 0.012 | N | 0.268 | neutral | N | 0.402421423 | None | None | I |
| P/M | 0.532 | ambiguous | 0.5385 | ambiguous | -0.461 | Destabilizing | 0.949 | D | 0.375 | neutral | None | None | None | None | I |
| P/N | 0.7031 | likely_pathogenic | 0.6962 | pathogenic | -0.688 | Destabilizing | 0.974 | D | 0.369 | neutral | None | None | None | None | I |
| P/Q | 0.2438 | likely_benign | 0.2567 | benign | -0.89 | Destabilizing | 0.136 | N | 0.189 | neutral | N | 0.405479025 | None | None | I |
| P/R | 0.2692 | likely_benign | 0.1926 | benign | -0.331 | Destabilizing | 0.669 | D | 0.381 | neutral | N | 0.434530289 | None | None | I |
| P/S | 0.2817 | likely_benign | 0.2905 | benign | -1.148 | Destabilizing | 0.801 | D | 0.293 | neutral | N | 0.438443689 | None | None | I |
| P/T | 0.2013 | likely_benign | 0.2145 | benign | -1.096 | Destabilizing | 0.891 | D | 0.282 | neutral | N | 0.442763599 | None | None | I |
| P/V | 0.3192 | likely_benign | 0.3258 | benign | -0.597 | Destabilizing | 0.728 | D | 0.359 | neutral | None | None | None | None | I |
| P/W | 0.8441 | likely_pathogenic | 0.8424 | pathogenic | -0.922 | Destabilizing | 0.998 | D | 0.49 | neutral | None | None | None | None | I |
| P/Y | 0.75 | likely_pathogenic | 0.7453 | pathogenic | -0.645 | Destabilizing | 0.991 | D | 0.403 | 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.