Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15193 | 45802;45803;45804 | chr2:178621141;178621140;178621139 | chr2:179485868;179485867;179485866 |
| N2AB | 13552 | 40879;40880;40881 | chr2:178621141;178621140;178621139 | chr2:179485868;179485867;179485866 |
| N2A | 12625 | 38098;38099;38100 | chr2:178621141;178621140;178621139 | chr2:179485868;179485867;179485866 |
| N2B | 6128 | 18607;18608;18609 | chr2:178621141;178621140;178621139 | chr2:179485868;179485867;179485866 |
| Novex-1 | 6253 | 18982;18983;18984 | chr2:178621141;178621140;178621139 | chr2:179485868;179485867;179485866 |
| Novex-2 | 6320 | 19183;19184;19185 | chr2:178621141;178621140;178621139 | chr2:179485868;179485867;179485866 |
| 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/A | rs1361317643  |
None | 0.002 | N | 0.257 | 0.167 | 0.413635276047 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94628E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs1361317643 |
None | 0.002 | N | 0.257 | 0.167 | 0.413635276047 | gnomAD-4.0.0 | 2.56618E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.4395E-05 | None | 0 | 0 | 0 | 1.34113E-05 | 0 |
| V/L | rs1435809981 |
-0.015 | 0.099 | N | 0.478 | 0.24 | 0.515317749148 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| V/L | rs1435809981 |
-0.015 | 0.099 | N | 0.478 | 0.24 | 0.515317749148 | gnomAD-4.0.0 | 3.18744E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57787E-05 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3963 | ambiguous | 0.4142 | ambiguous | -1.701 | Destabilizing | 0.002 | N | 0.257 | neutral | N | 0.441656435 | None | None | N |
| V/C | 0.9529 | likely_pathogenic | 0.9365 | pathogenic | -1.121 | Destabilizing | 0.977 | D | 0.785 | deleterious | None | None | None | None | N |
| V/D | 0.9589 | likely_pathogenic | 0.9624 | pathogenic | -2.548 | Highly Destabilizing | 0.92 | D | 0.833 | deleterious | None | None | None | None | N |
| V/E | 0.938 | likely_pathogenic | 0.9412 | pathogenic | -2.339 | Highly Destabilizing | 0.81 | D | 0.794 | deleterious | D | 0.524769958 | None | None | N |
| V/F | 0.7441 | likely_pathogenic | 0.7696 | pathogenic | -0.962 | Destabilizing | 0.85 | D | 0.807 | deleterious | None | None | None | None | N |
| V/G | 0.6999 | likely_pathogenic | 0.7459 | pathogenic | -2.215 | Highly Destabilizing | 0.379 | N | 0.777 | deleterious | D | 0.527504829 | None | None | N |
| V/H | 0.9817 | likely_pathogenic | 0.9828 | pathogenic | -2.185 | Highly Destabilizing | 0.992 | D | 0.817 | deleterious | None | None | None | None | N |
| V/I | 0.1379 | likely_benign | 0.1414 | benign | -0.279 | Destabilizing | 0.002 | N | 0.201 | neutral | N | 0.475092951 | None | None | N |
| V/K | 0.9681 | likely_pathogenic | 0.9699 | pathogenic | -1.481 | Destabilizing | 0.85 | D | 0.796 | deleterious | None | None | None | None | N |
| V/L | 0.6177 | likely_pathogenic | 0.6576 | pathogenic | -0.279 | Destabilizing | 0.099 | N | 0.478 | neutral | N | 0.514781534 | None | None | N |
| V/M | 0.666 | likely_pathogenic | 0.6898 | pathogenic | -0.288 | Destabilizing | 0.85 | D | 0.691 | prob.neutral | None | None | None | None | N |
| V/N | 0.9214 | likely_pathogenic | 0.9243 | pathogenic | -1.765 | Destabilizing | 0.92 | D | 0.843 | deleterious | None | None | None | None | N |
| V/P | 0.9698 | likely_pathogenic | 0.973 | pathogenic | -0.725 | Destabilizing | 0.92 | D | 0.823 | deleterious | None | None | None | None | N |
| V/Q | 0.9523 | likely_pathogenic | 0.9552 | pathogenic | -1.613 | Destabilizing | 0.92 | D | 0.821 | deleterious | None | None | None | None | N |
| V/R | 0.9369 | likely_pathogenic | 0.9414 | pathogenic | -1.368 | Destabilizing | 0.85 | D | 0.843 | deleterious | None | None | None | None | N |
| V/S | 0.741 | likely_pathogenic | 0.7504 | pathogenic | -2.282 | Highly Destabilizing | 0.447 | N | 0.762 | deleterious | None | None | None | None | N |
| V/T | 0.549 | ambiguous | 0.55 | ambiguous | -1.944 | Destabilizing | 0.617 | D | 0.679 | prob.neutral | None | None | None | None | N |
| V/W | 0.9928 | likely_pathogenic | 0.9928 | pathogenic | -1.602 | Destabilizing | 0.992 | D | 0.809 | deleterious | None | None | None | None | N |
| V/Y | 0.9662 | likely_pathogenic | 0.9658 | pathogenic | -1.139 | Destabilizing | 0.972 | D | 0.808 | 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.