Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35468 | 106627;106628;106629 | chr2:178530089;178530088;178530087 | chr2:179394816;179394815;179394814 |
| N2AB | 33827 | 101704;101705;101706 | chr2:178530089;178530088;178530087 | chr2:179394816;179394815;179394814 |
| N2A | 32900 | 98923;98924;98925 | chr2:178530089;178530088;178530087 | chr2:179394816;179394815;179394814 |
| N2B | 26403 | 79432;79433;79434 | chr2:178530089;178530088;178530087 | chr2:179394816;179394815;179394814 |
| Novex-1 | 26528 | 79807;79808;79809 | chr2:178530089;178530088;178530087 | chr2:179394816;179394815;179394814 |
| Novex-2 | 26595 | 80008;80009;80010 | chr2:178530089;178530088;178530087 | chr2:179394816;179394815;179394814 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/H | rs952475900  |
-1.752 | 0.993 | N | 0.768 | 0.595 | 0.809486353647 | gnomAD-2.1.1 | 8.32E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.81E-05 | 0 |
| L/H | rs952475900 |
-1.752 | 0.993 | N | 0.768 | 0.595 | 0.809486353647 | gnomAD-4.0.0 | 1.99363E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.52215E-05 | 0 | 1.66301E-05 |
| L/P | None | None | 0.975 | N | 0.789 | 0.591 | 0.789849054134 | gnomAD-4.0.0 | 1.37492E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80154E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.3078 | likely_benign | 0.3216 | benign | -2.058 | Highly Destabilizing | 0.705 | D | 0.531 | neutral | None | None | None | None | N |
| L/C | 0.5719 | likely_pathogenic | 0.558 | ambiguous | -1.166 | Destabilizing | 0.995 | D | 0.69 | prob.neutral | None | None | None | None | N |
| L/D | 0.7229 | likely_pathogenic | 0.7423 | pathogenic | -1.659 | Destabilizing | 0.981 | D | 0.791 | deleterious | None | None | None | None | N |
| L/E | 0.428 | ambiguous | 0.441 | ambiguous | -1.574 | Destabilizing | 0.981 | D | 0.778 | deleterious | None | None | None | None | N |
| L/F | 0.1409 | likely_benign | 0.1364 | benign | -1.334 | Destabilizing | 0.863 | D | 0.598 | neutral | N | 0.493559793 | None | None | N |
| L/G | 0.5719 | likely_pathogenic | 0.6015 | pathogenic | -2.479 | Highly Destabilizing | 0.944 | D | 0.769 | deleterious | None | None | None | None | N |
| L/H | 0.2938 | likely_benign | 0.2987 | benign | -1.763 | Destabilizing | 0.993 | D | 0.768 | deleterious | N | 0.499623664 | None | None | N |
| L/I | 0.0737 | likely_benign | 0.0735 | benign | -0.921 | Destabilizing | 0.006 | N | 0.239 | neutral | N | 0.41348007 | None | None | N |
| L/K | 0.3332 | likely_benign | 0.3481 | ambiguous | -1.453 | Destabilizing | 0.944 | D | 0.737 | prob.delet. | None | None | None | None | N |
| L/M | 0.1317 | likely_benign | 0.1333 | benign | -0.663 | Destabilizing | 0.893 | D | 0.65 | neutral | None | None | None | None | N |
| L/N | 0.4357 | ambiguous | 0.4641 | ambiguous | -1.37 | Destabilizing | 0.981 | D | 0.789 | deleterious | None | None | None | None | N |
| L/P | 0.4932 | ambiguous | 0.5046 | ambiguous | -1.272 | Destabilizing | 0.975 | D | 0.789 | deleterious | N | 0.505182296 | None | None | N |
| L/Q | 0.2227 | likely_benign | 0.2283 | benign | -1.444 | Destabilizing | 0.981 | D | 0.759 | deleterious | None | None | None | None | N |
| L/R | 0.2476 | likely_benign | 0.2545 | benign | -0.948 | Destabilizing | 0.928 | D | 0.765 | deleterious | D | 0.531406106 | None | None | N |
| L/S | 0.3622 | ambiguous | 0.3828 | ambiguous | -2.046 | Highly Destabilizing | 0.944 | D | 0.721 | prob.delet. | None | None | None | None | N |
| L/T | 0.247 | likely_benign | 0.2606 | benign | -1.834 | Destabilizing | 0.893 | D | 0.665 | neutral | None | None | None | None | N |
| L/V | 0.0986 | likely_benign | 0.0981 | benign | -1.272 | Destabilizing | 0.114 | N | 0.366 | neutral | N | 0.453054391 | None | None | N |
| L/W | 0.2746 | likely_benign | 0.2696 | benign | -1.534 | Destabilizing | 0.995 | D | 0.728 | prob.delet. | None | None | None | None | N |
| L/Y | 0.3365 | likely_benign | 0.3405 | ambiguous | -1.287 | Destabilizing | 0.944 | D | 0.717 | prob.delet. | 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.