Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20999 | 63220;63221;63222 | chr2:178588730;178588729;178588728 | chr2:179453457;179453456;179453455 |
| N2AB | 19358 | 58297;58298;58299 | chr2:178588730;178588729;178588728 | chr2:179453457;179453456;179453455 |
| N2A | 18431 | 55516;55517;55518 | chr2:178588730;178588729;178588728 | chr2:179453457;179453456;179453455 |
| N2B | 11934 | 36025;36026;36027 | chr2:178588730;178588729;178588728 | chr2:179453457;179453456;179453455 |
| Novex-1 | 12059 | 36400;36401;36402 | chr2:178588730;178588729;178588728 | chr2:179453457;179453456;179453455 |
| Novex-2 | 12126 | 36601;36602;36603 | chr2:178588730;178588729;178588728 | chr2:179453457;179453456;179453455 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs568886353  |
None | None | N | 0.19 | 0.098 | 0.112648838833 | gnomAD-4.0.0 | 1.36885E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79932E-06 | 0 | 0 |
| F/S | None | None | 0.014 | N | 0.466 | 0.2 | 0.226586394389 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| F/V | rs568886353 |
-2.107 | None | N | 0.253 | 0.121 | None | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.61309E-04 | None | 0 | None | 0 | 0 | 0 |
| F/V | rs568886353 |
-2.107 | None | N | 0.253 | 0.121 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 7.76398E-04 | None | 0 | 0 | 0 | 0 | 0 |
| F/V | rs568886353 |
-2.107 | None | N | 0.253 | 0.121 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| F/V | rs568886353 |
-2.107 | None | N | 0.253 | 0.121 | None | gnomAD-4.0.0 | 1.48771E-05 | None | None | None | None | N | None | 0 | 1.66778E-05 | None | 0 | 3.12961E-04 | None | 0 | 0 | 0 | 0 | 1.44083E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.6549 | likely_pathogenic | 0.6184 | pathogenic | -2.912 | Highly Destabilizing | 0.008 | N | 0.431 | neutral | None | None | None | None | N |
| F/C | 0.2018 | likely_benign | 0.2025 | benign | -1.645 | Destabilizing | 0.427 | N | 0.597 | neutral | N | 0.472189152 | None | None | N |
| F/D | 0.8834 | likely_pathogenic | 0.8886 | pathogenic | -2.497 | Highly Destabilizing | 0.085 | N | 0.557 | neutral | None | None | None | None | N |
| F/E | 0.8642 | likely_pathogenic | 0.8635 | pathogenic | -2.385 | Highly Destabilizing | 0.085 | N | 0.569 | neutral | None | None | None | None | N |
| F/G | 0.8798 | likely_pathogenic | 0.8696 | pathogenic | -3.275 | Highly Destabilizing | 0.037 | N | 0.512 | neutral | None | None | None | None | N |
| F/H | 0.3198 | likely_benign | 0.319 | benign | -1.531 | Destabilizing | 0.138 | N | 0.544 | neutral | None | None | None | None | N |
| F/I | 0.0928 | likely_benign | 0.0874 | benign | -1.766 | Destabilizing | None | N | 0.143 | neutral | N | 0.368869996 | None | None | N |
| F/K | 0.7837 | likely_pathogenic | 0.7853 | pathogenic | -1.714 | Destabilizing | 0.044 | N | 0.571 | neutral | None | None | None | None | N |
| F/L | 0.6107 | likely_pathogenic | 0.5949 | pathogenic | -1.766 | Destabilizing | None | N | 0.19 | neutral | N | 0.409119108 | None | None | N |
| F/M | 0.3667 | ambiguous | 0.3434 | ambiguous | -1.398 | Destabilizing | 0.138 | N | 0.469 | neutral | None | None | None | None | N |
| F/N | 0.5365 | ambiguous | 0.5751 | pathogenic | -1.831 | Destabilizing | 0.085 | N | 0.584 | neutral | None | None | None | None | N |
| F/P | 0.9973 | likely_pathogenic | 0.9974 | pathogenic | -2.15 | Highly Destabilizing | 0.22 | N | 0.614 | neutral | None | None | None | None | N |
| F/Q | 0.6637 | likely_pathogenic | 0.6636 | pathogenic | -1.985 | Destabilizing | 0.245 | N | 0.609 | neutral | None | None | None | None | N |
| F/R | 0.6281 | likely_pathogenic | 0.6486 | pathogenic | -0.929 | Destabilizing | 0.044 | N | 0.605 | neutral | None | None | None | None | N |
| F/S | 0.4855 | ambiguous | 0.458 | ambiguous | -2.573 | Highly Destabilizing | 0.014 | N | 0.466 | neutral | N | 0.437535073 | None | None | N |
| F/T | 0.4947 | ambiguous | 0.4848 | ambiguous | -2.369 | Highly Destabilizing | 0.018 | N | 0.47 | neutral | None | None | None | None | N |
| F/V | 0.1434 | likely_benign | 0.1314 | benign | -2.15 | Highly Destabilizing | None | N | 0.253 | neutral | N | 0.41054326 | None | None | N |
| F/W | 0.3582 | ambiguous | 0.3694 | ambiguous | -0.727 | Destabilizing | 0.245 | N | 0.481 | neutral | None | None | None | None | N |
| F/Y | 0.0778 | likely_benign | 0.089 | benign | -1.019 | Destabilizing | None | N | 0.161 | neutral | N | 0.394632445 | 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.