Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31085 | 93478;93479;93480 | chr2:178548373;178548372;178548371 | chr2:179413100;179413099;179413098 |
| N2AB | 29444 | 88555;88556;88557 | chr2:178548373;178548372;178548371 | chr2:179413100;179413099;179413098 |
| N2A | 28517 | 85774;85775;85776 | chr2:178548373;178548372;178548371 | chr2:179413100;179413099;179413098 |
| N2B | 22020 | 66283;66284;66285 | chr2:178548373;178548372;178548371 | chr2:179413100;179413099;179413098 |
| Novex-1 | 22145 | 66658;66659;66660 | chr2:178548373;178548372;178548371 | chr2:179413100;179413099;179413098 |
| Novex-2 | 22212 | 66859;66860;66861 | chr2:178548373;178548372;178548371 | chr2:179413100;179413099;179413098 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs549841864  |
0.194 | 0.999 | N | 0.748 | 0.417 | None | gnomAD-2.1.1 | 1.39443E-04 | None | None | None | None | N | None | 4.13E-05 | 2.83E-05 | None | 0 | 1.58811E-03 | None | 1.30719E-04 | None | 0 | 0 | 2.81215E-04 |
| P/L | rs549841864 |
0.194 | 0.999 | N | 0.748 | 0.417 | None | gnomAD-3.1.2 | 1.05193E-04 | None | None | None | None | N | None | 2.41E-05 | 6.56E-05 | 0 | 0 | 2.12028E-03 | None | 0 | 0 | 0 | 6.22407E-04 | 0 |
| P/L | rs549841864 |
0.194 | 0.999 | N | 0.748 | 0.417 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| P/L | rs549841864 |
0.194 | 0.999 | N | 0.748 | 0.417 | None | gnomAD-4.0.0 | 7.31195E-05 | None | None | None | None | N | None | 2.6661E-05 | 3.33367E-05 | None | 0 | 1.69356E-03 | None | 0 | 0 | 1.35615E-05 | 1.64701E-04 | 1.12025E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0903 | likely_benign | 0.0868 | benign | -1.343 | Destabilizing | 0.37 | N | 0.333 | neutral | N | 0.425704714 | None | None | N |
| P/C | 0.5865 | likely_pathogenic | 0.5641 | pathogenic | -0.663 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| P/D | 0.777 | likely_pathogenic | 0.7719 | pathogenic | -1.106 | Destabilizing | 0.998 | D | 0.721 | prob.delet. | None | None | None | None | N |
| P/E | 0.5955 | likely_pathogenic | 0.5719 | pathogenic | -1.025 | Destabilizing | 0.998 | D | 0.722 | prob.delet. | None | None | None | None | N |
| P/F | 0.6698 | likely_pathogenic | 0.6675 | pathogenic | -0.836 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| P/G | 0.4176 | ambiguous | 0.3993 | ambiguous | -1.735 | Destabilizing | 0.967 | D | 0.637 | neutral | None | None | None | None | N |
| P/H | 0.3892 | ambiguous | 0.4008 | ambiguous | -1.315 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| P/I | 0.4966 | ambiguous | 0.4674 | ambiguous | -0.338 | Destabilizing | 0.995 | D | 0.805 | deleterious | None | None | None | None | N |
| P/K | 0.6778 | likely_pathogenic | 0.6544 | pathogenic | -0.999 | Destabilizing | 0.995 | D | 0.719 | prob.delet. | None | None | None | None | N |
| P/L | 0.185 | likely_benign | 0.1814 | benign | -0.338 | Destabilizing | 0.999 | D | 0.748 | deleterious | N | 0.398403469 | None | None | N |
| P/M | 0.4609 | ambiguous | 0.4518 | ambiguous | -0.22 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| P/N | 0.54 | ambiguous | 0.549 | ambiguous | -0.932 | Destabilizing | 0.998 | D | 0.789 | deleterious | None | None | None | None | N |
| P/Q | 0.3085 | likely_benign | 0.3207 | benign | -0.966 | Destabilizing | 1.0 | D | 0.792 | deleterious | N | 0.411812697 | None | None | N |
| P/R | 0.4524 | ambiguous | 0.4479 | ambiguous | -0.659 | Destabilizing | 0.999 | D | 0.798 | deleterious | N | 0.449773652 | None | None | N |
| P/S | 0.1664 | likely_benign | 0.1643 | benign | -1.515 | Destabilizing | 0.956 | D | 0.586 | neutral | N | 0.359365078 | None | None | N |
| P/T | 0.1697 | likely_benign | 0.1661 | benign | -1.313 | Destabilizing | 0.576 | D | 0.307 | neutral | N | 0.38514617 | None | None | N |
| P/V | 0.3408 | ambiguous | 0.3175 | benign | -0.639 | Destabilizing | 0.983 | D | 0.661 | neutral | None | None | None | None | N |
| P/W | 0.829 | likely_pathogenic | 0.8256 | pathogenic | -1.171 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| P/Y | 0.658 | likely_pathogenic | 0.6533 | pathogenic | -0.79 | Destabilizing | 1.0 | D | 0.795 | 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.