Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35140 | 105643;105644;105645 | chr2:178531197;178531196;178531195 | chr2:179395924;179395923;179395922 |
| N2AB | 33499 | 100720;100721;100722 | chr2:178531197;178531196;178531195 | chr2:179395924;179395923;179395922 |
| N2A | 32572 | 97939;97940;97941 | chr2:178531197;178531196;178531195 | chr2:179395924;179395923;179395922 |
| N2B | 26075 | 78448;78449;78450 | chr2:178531197;178531196;178531195 | chr2:179395924;179395923;179395922 |
| Novex-1 | 26200 | 78823;78824;78825 | chr2:178531197;178531196;178531195 | chr2:179395924;179395923;179395922 |
| Novex-2 | 26267 | 79024;79025;79026 | chr2:178531197;178531196;178531195 | chr2:179395924;179395923;179395922 |
| 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 | 0.978 | D | 0.726 | 0.563 | 0.863341754641 | gnomAD-4.0.0 | 6.84137E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99394E-07 | 0 | 0 |
| V/I | rs371893623  |
-0.428 | 0.081 | D | 0.321 | 0.245 | None | gnomAD-2.1.1 | 3.21E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.24E-05 | 0 |
| V/I | rs371893623 |
-0.428 | 0.081 | D | 0.321 | 0.245 | None | gnomAD-3.1.2 | 5.91E-05 | None | None | None | None | N | None | 1.2068E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| V/I | rs371893623 |
-0.428 | 0.081 | D | 0.321 | 0.245 | None | gnomAD-4.0.0 | 4.52332E-05 | None | None | None | None | N | None | 1.06798E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 5.0852E-05 | 1.09786E-05 | 6.40348E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2941 | likely_benign | 0.3596 | ambiguous | -1.816 | Destabilizing | 0.834 | D | 0.47 | neutral | N | 0.487230628 | None | None | N |
| V/C | 0.8695 | likely_pathogenic | 0.8481 | pathogenic | -1.283 | Destabilizing | 0.998 | D | 0.665 | neutral | None | None | None | None | N |
| V/D | 0.8687 | likely_pathogenic | 0.9163 | pathogenic | -2.165 | Highly Destabilizing | 0.973 | D | 0.753 | deleterious | D | 0.568186932 | None | None | N |
| V/E | 0.7691 | likely_pathogenic | 0.8292 | pathogenic | -2.044 | Highly Destabilizing | 0.979 | D | 0.691 | prob.neutral | None | None | None | None | N |
| V/F | 0.3118 | likely_benign | 0.396 | ambiguous | -1.172 | Destabilizing | 0.978 | D | 0.726 | prob.delet. | D | 0.526445013 | None | None | N |
| V/G | 0.4947 | ambiguous | 0.5799 | pathogenic | -2.261 | Highly Destabilizing | 0.973 | D | 0.732 | prob.delet. | D | 0.52817976 | None | None | N |
| V/H | 0.897 | likely_pathogenic | 0.9185 | pathogenic | -1.992 | Destabilizing | 0.998 | D | 0.697 | prob.neutral | None | None | None | None | N |
| V/I | 0.0833 | likely_benign | 0.0879 | benign | -0.627 | Destabilizing | 0.081 | N | 0.321 | neutral | D | 0.538892225 | None | None | N |
| V/K | 0.7843 | likely_pathogenic | 0.7985 | pathogenic | -1.465 | Destabilizing | 0.979 | D | 0.693 | prob.neutral | None | None | None | None | N |
| V/L | 0.2774 | likely_benign | 0.3418 | ambiguous | -0.627 | Destabilizing | 0.476 | N | 0.471 | neutral | N | 0.504982942 | None | None | N |
| V/M | 0.2441 | likely_benign | 0.2956 | benign | -0.578 | Destabilizing | 0.959 | D | 0.767 | deleterious | None | None | None | None | N |
| V/N | 0.7357 | likely_pathogenic | 0.8023 | pathogenic | -1.51 | Destabilizing | 0.993 | D | 0.752 | deleterious | None | None | None | None | N |
| V/P | 0.9544 | likely_pathogenic | 0.9651 | pathogenic | -0.993 | Destabilizing | 0.993 | D | 0.721 | prob.delet. | None | None | None | None | N |
| V/Q | 0.7525 | likely_pathogenic | 0.788 | pathogenic | -1.511 | Destabilizing | 0.993 | D | 0.708 | prob.delet. | None | None | None | None | N |
| V/R | 0.6866 | likely_pathogenic | 0.688 | pathogenic | -1.159 | Destabilizing | 0.979 | D | 0.743 | deleterious | None | None | None | None | N |
| V/S | 0.5067 | ambiguous | 0.5872 | pathogenic | -2.083 | Highly Destabilizing | 0.979 | D | 0.705 | prob.neutral | None | None | None | None | N |
| V/T | 0.3504 | ambiguous | 0.3979 | ambiguous | -1.84 | Destabilizing | 0.87 | D | 0.663 | neutral | None | None | None | None | N |
| V/W | 0.9523 | likely_pathogenic | 0.9663 | pathogenic | -1.601 | Destabilizing | 0.998 | D | 0.665 | neutral | None | None | None | None | N |
| V/Y | 0.8482 | likely_pathogenic | 0.8776 | pathogenic | -1.235 | Destabilizing | 0.979 | D | 0.739 | 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.