Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35022 | 105289;105290;105291 | chr2:178531551;178531550;178531549 | chr2:179396278;179396277;179396276 |
| N2AB | 33381 | 100366;100367;100368 | chr2:178531551;178531550;178531549 | chr2:179396278;179396277;179396276 |
| N2A | 32454 | 97585;97586;97587 | chr2:178531551;178531550;178531549 | chr2:179396278;179396277;179396276 |
| N2B | 25957 | 78094;78095;78096 | chr2:178531551;178531550;178531549 | chr2:179396278;179396277;179396276 |
| Novex-1 | 26082 | 78469;78470;78471 | chr2:178531551;178531550;178531549 | chr2:179396278;179396277;179396276 |
| Novex-2 | 26149 | 78670;78671;78672 | chr2:178531551;178531550;178531549 | chr2:179396278;179396277;179396276 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/K | rs727504977  |
0.524 | 1.0 | D | 0.677 | 0.465 | 0.441636318388 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| E/K | rs727504977 |
0.524 | 1.0 | D | 0.677 | 0.465 | 0.441636318388 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| E/K | rs727504977 |
0.524 | 1.0 | D | 0.677 | 0.465 | 0.441636318388 | gnomAD-4.0.0 | 5.57677E-06 | None | None | None | None | N | None | 0 | 1.66672E-05 | None | 0 | 2.22747E-05 | None | 0 | 0 | 5.93281E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.4266 | ambiguous | 0.5587 | ambiguous | -0.572 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | N | 0.497141675 | None | None | N |
| E/C | 0.985 | likely_pathogenic | 0.9899 | pathogenic | 0.06 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| E/D | 0.4312 | ambiguous | 0.6046 | pathogenic | -0.464 | Destabilizing | 0.999 | D | 0.476 | neutral | N | 0.520614754 | None | None | N |
| E/F | 0.9532 | likely_pathogenic | 0.9708 | pathogenic | -0.573 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| E/G | 0.6128 | likely_pathogenic | 0.7172 | pathogenic | -0.774 | Destabilizing | 1.0 | D | 0.657 | neutral | N | 0.503435552 | None | None | N |
| E/H | 0.8868 | likely_pathogenic | 0.9321 | pathogenic | -0.538 | Destabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| E/I | 0.7123 | likely_pathogenic | 0.8054 | pathogenic | -0.069 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| E/K | 0.4438 | ambiguous | 0.5575 | ambiguous | 0.296 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | D | 0.532595397 | None | None | N |
| E/L | 0.8325 | likely_pathogenic | 0.9001 | pathogenic | -0.069 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| E/M | 0.7472 | likely_pathogenic | 0.8201 | pathogenic | 0.238 | Stabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| E/N | 0.6808 | likely_pathogenic | 0.8203 | pathogenic | 0.021 | Stabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| E/P | 0.986 | likely_pathogenic | 0.9937 | pathogenic | -0.217 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| E/Q | 0.3485 | ambiguous | 0.451 | ambiguous | 0.024 | Stabilizing | 1.0 | D | 0.627 | neutral | D | 0.524978779 | None | None | N |
| E/R | 0.7059 | likely_pathogenic | 0.783 | pathogenic | 0.386 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| E/S | 0.4748 | ambiguous | 0.6406 | pathogenic | -0.154 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | N |
| E/T | 0.485 | ambiguous | 0.6427 | pathogenic | 0.01 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| E/V | 0.4748 | ambiguous | 0.5908 | pathogenic | -0.217 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.521375223 | None | None | N |
| E/W | 0.991 | likely_pathogenic | 0.9944 | pathogenic | -0.421 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| E/Y | 0.9453 | likely_pathogenic | 0.9659 | pathogenic | -0.322 | Destabilizing | 1.0 | D | 0.667 | neutral | 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.