Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17510 | 52753;52754;52755 | chr2:178608355;178608354;178608353 | chr2:179473082;179473081;179473080 |
| N2AB | 15869 | 47830;47831;47832 | chr2:178608355;178608354;178608353 | chr2:179473082;179473081;179473080 |
| N2A | 14942 | 45049;45050;45051 | chr2:178608355;178608354;178608353 | chr2:179473082;179473081;179473080 |
| N2B | 8445 | 25558;25559;25560 | chr2:178608355;178608354;178608353 | chr2:179473082;179473081;179473080 |
| Novex-1 | 8570 | 25933;25934;25935 | chr2:178608355;178608354;178608353 | chr2:179473082;179473081;179473080 |
| Novex-2 | 8637 | 26134;26135;26136 | chr2:178608355;178608354;178608353 | chr2:179473082;179473081;179473080 |
| 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/D | None | None | 0.999 | N | 0.441 | 0.278 | 0.344251166708 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| E/K | rs754803968  |
-1.265 | 0.999 | N | 0.559 | 0.367 | 0.377976839388 | gnomAD-2.1.1 | 8.12E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.8E-05 | 0 |
| E/K | rs754803968 |
-1.265 | 0.999 | N | 0.559 | 0.367 | 0.377976839388 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| E/K | rs754803968 |
-1.265 | 0.999 | N | 0.559 | 0.367 | 0.377976839388 | gnomAD-4.0.0 | 3.85166E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19114E-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 | 0.9085 | likely_pathogenic | 0.8459 | pathogenic | -1.129 | Destabilizing | 0.999 | D | 0.631 | neutral | N | 0.484588422 | None | None | N |
| E/C | 0.9936 | likely_pathogenic | 0.9904 | pathogenic | -0.535 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| E/D | 0.7595 | likely_pathogenic | 0.6262 | pathogenic | -1.078 | Destabilizing | 0.999 | D | 0.441 | neutral | N | 0.504282927 | None | None | N |
| E/F | 0.9975 | likely_pathogenic | 0.9957 | pathogenic | -0.539 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| E/G | 0.9381 | likely_pathogenic | 0.903 | pathogenic | -1.487 | Destabilizing | 1.0 | D | 0.673 | neutral | N | 0.492185746 | None | None | N |
| E/H | 0.9874 | likely_pathogenic | 0.9747 | pathogenic | -0.701 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| E/I | 0.9824 | likely_pathogenic | 0.9742 | pathogenic | -0.144 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| E/K | 0.9608 | likely_pathogenic | 0.9372 | pathogenic | -0.56 | Destabilizing | 0.999 | D | 0.559 | neutral | N | 0.511862261 | None | None | N |
| E/L | 0.9817 | likely_pathogenic | 0.9692 | pathogenic | -0.144 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| E/M | 0.9801 | likely_pathogenic | 0.9666 | pathogenic | 0.369 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| E/N | 0.9693 | likely_pathogenic | 0.9424 | pathogenic | -1.112 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| E/P | 0.9859 | likely_pathogenic | 0.9714 | pathogenic | -0.452 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| E/Q | 0.8873 | likely_pathogenic | 0.8229 | pathogenic | -0.995 | Destabilizing | 1.0 | D | 0.616 | neutral | N | 0.475736878 | None | None | N |
| E/R | 0.9669 | likely_pathogenic | 0.951 | pathogenic | -0.258 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| E/S | 0.9551 | likely_pathogenic | 0.9274 | pathogenic | -1.431 | Destabilizing | 0.999 | D | 0.603 | neutral | None | None | None | None | N |
| E/T | 0.9801 | likely_pathogenic | 0.967 | pathogenic | -1.122 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| E/V | 0.9553 | likely_pathogenic | 0.9325 | pathogenic | -0.452 | Destabilizing | 1.0 | D | 0.769 | deleterious | N | 0.486754469 | None | None | N |
| E/W | 0.9987 | likely_pathogenic | 0.9977 | pathogenic | -0.198 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| E/Y | 0.9948 | likely_pathogenic | 0.9912 | pathogenic | -0.252 | Destabilizing | 1.0 | D | 0.737 | 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.