Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31301 | 94126;94127;94128 | chr2:178547725;178547724;178547723 | chr2:179412452;179412451;179412450 |
| N2AB | 29660 | 89203;89204;89205 | chr2:178547725;178547724;178547723 | chr2:179412452;179412451;179412450 |
| N2A | 28733 | 86422;86423;86424 | chr2:178547725;178547724;178547723 | chr2:179412452;179412451;179412450 |
| N2B | 22236 | 66931;66932;66933 | chr2:178547725;178547724;178547723 | chr2:179412452;179412451;179412450 |
| Novex-1 | 22361 | 67306;67307;67308 | chr2:178547725;178547724;178547723 | chr2:179412452;179412451;179412450 |
| Novex-2 | 22428 | 67507;67508;67509 | chr2:178547725;178547724;178547723 | chr2:179412452;179412451;179412450 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | None | None | 0.715 | N | 0.751 | 0.286 | 0.502568190621 | gnomAD-4.0.0 | 6.84168E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99423E-07 | 0 | 0 |
| V/I | rs67665715  |
0.101 | 0.002 | N | 0.202 | 0.108 | None | gnomAD-2.1.1 | 1.1064E-02 | None | None | None | None | N | None | 1.12127E-01 | 5.54455E-03 | None | 5.51044E-03 | 5.13E-05 | None | 2.94098E-04 | None | 0 | 7.49134E-04 | 4.34783E-03 |
| V/I | rs67665715 |
0.101 | 0.002 | N | 0.202 | 0.108 | None | gnomAD-3.1.2 | 3.25484E-02 | None | None | None | None | N | None | 1.11887E-01 | 1.27701E-02 | 0 | 6.33641E-03 | 1.92901E-04 | None | 0 | 6.32911E-03 | 7.49824E-04 | 4.14422E-04 | 2.15517E-02 |
| V/I | rs67665715 |
0.101 | 0.002 | N | 0.202 | 0.108 | None | 1000 genomes | 3.59425E-02 | None | None | None | None | N | None | 1.271E-01 | 1.59E-02 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| V/I | rs67665715 |
0.101 | 0.002 | N | 0.202 | 0.108 | None | gnomAD-4.0.0 | 6.58297E-03 | None | None | None | None | N | None | 1.14873E-01 | 7.7823E-03 | None | 6.89049E-03 | 6.68717E-05 | None | 1.56196E-05 | 6.26856E-03 | 6.20427E-04 | 2.63505E-04 | 8.64277E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6509 | likely_pathogenic | 0.585 | pathogenic | -2.037 | Highly Destabilizing | 0.104 | N | 0.576 | neutral | D | 0.527168148 | None | None | N |
| V/C | 0.8377 | likely_pathogenic | 0.7985 | pathogenic | -1.708 | Destabilizing | 0.968 | D | 0.731 | prob.delet. | None | None | None | None | N |
| V/D | 0.9915 | likely_pathogenic | 0.985 | pathogenic | -2.687 | Highly Destabilizing | 0.667 | D | 0.815 | deleterious | N | 0.520805792 | None | None | N |
| V/E | 0.9789 | likely_pathogenic | 0.9675 | pathogenic | -2.427 | Highly Destabilizing | 0.726 | D | 0.777 | deleterious | None | None | None | None | N |
| V/F | 0.3515 | ambiguous | 0.3583 | ambiguous | -1.192 | Destabilizing | 0.715 | D | 0.751 | deleterious | N | 0.510222757 | None | None | N |
| V/G | 0.856 | likely_pathogenic | 0.809 | pathogenic | -2.628 | Highly Destabilizing | 0.667 | D | 0.793 | deleterious | N | 0.520552302 | None | None | N |
| V/H | 0.986 | likely_pathogenic | 0.9773 | pathogenic | -2.49 | Highly Destabilizing | 0.968 | D | 0.791 | deleterious | None | None | None | None | N |
| V/I | 0.0647 | likely_benign | 0.0688 | benign | -0.37 | Destabilizing | 0.002 | N | 0.202 | neutral | N | 0.458735144 | None | None | N |
| V/K | 0.9792 | likely_pathogenic | 0.9677 | pathogenic | -1.717 | Destabilizing | 0.726 | D | 0.779 | deleterious | None | None | None | None | N |
| V/L | 0.2105 | likely_benign | 0.1993 | benign | -0.37 | Destabilizing | 0.022 | N | 0.406 | neutral | N | 0.511489406 | None | None | N |
| V/M | 0.2485 | likely_benign | 0.2336 | benign | -0.522 | Destabilizing | 0.567 | D | 0.655 | neutral | None | None | None | None | N |
| V/N | 0.9668 | likely_pathogenic | 0.9442 | pathogenic | -2.159 | Highly Destabilizing | 0.89 | D | 0.82 | deleterious | None | None | None | None | N |
| V/P | 0.9844 | likely_pathogenic | 0.9763 | pathogenic | -0.899 | Destabilizing | 0.89 | D | 0.758 | deleterious | None | None | None | None | N |
| V/Q | 0.9708 | likely_pathogenic | 0.9519 | pathogenic | -1.915 | Destabilizing | 0.89 | D | 0.776 | deleterious | None | None | None | None | N |
| V/R | 0.9668 | likely_pathogenic | 0.9486 | pathogenic | -1.684 | Destabilizing | 0.726 | D | 0.821 | deleterious | None | None | None | None | N |
| V/S | 0.8972 | likely_pathogenic | 0.8426 | pathogenic | -2.801 | Highly Destabilizing | 0.726 | D | 0.753 | deleterious | None | None | None | None | N |
| V/T | 0.7734 | likely_pathogenic | 0.6961 | pathogenic | -2.377 | Highly Destabilizing | 0.272 | N | 0.643 | neutral | None | None | None | None | N |
| V/W | 0.978 | likely_pathogenic | 0.9701 | pathogenic | -1.758 | Destabilizing | 0.968 | D | 0.78 | deleterious | None | None | None | None | N |
| V/Y | 0.9196 | likely_pathogenic | 0.8971 | pathogenic | -1.342 | Destabilizing | 0.726 | D | 0.757 | 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.