Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28658 | 86197;86198;86199 | chr2:178560160;178560159;178560158 | chr2:179424887;179424886;179424885 |
| N2AB | 27017 | 81274;81275;81276 | chr2:178560160;178560159;178560158 | chr2:179424887;179424886;179424885 |
| N2A | 26090 | 78493;78494;78495 | chr2:178560160;178560159;178560158 | chr2:179424887;179424886;179424885 |
| N2B | 19593 | 59002;59003;59004 | chr2:178560160;178560159;178560158 | chr2:179424887;179424886;179424885 |
| Novex-1 | 19718 | 59377;59378;59379 | chr2:178560160;178560159;178560158 | chr2:179424887;179424886;179424885 |
| Novex-2 | 19785 | 59578;59579;59580 | chr2:178560160;178560159;178560158 | chr2:179424887;179424886;179424885 |
| 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 | rs1703118451  |
None | 0.976 | N | 0.841 | 0.379 | 0.431602765429 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.79386E-04 |
| P/L | rs1703118451 |
None | 0.976 | N | 0.841 | 0.379 | 0.431602765429 | gnomAD-4.0.0 | 6.57808E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.79386E-04 |
| P/S | rs772534573 |
-1.871 | 0.994 | D | 0.836 | 0.429 | 0.354183961838 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 1.78E-05 | 0 |
| P/S | rs772534573 |
-1.871 | 0.994 | D | 0.836 | 0.429 | 0.354183961838 | gnomAD-4.0.0 | 1.43231E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 4.83092E-04 | 2.85879E-06 | 7.16456E-05 | 3.02389E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.5791 | likely_pathogenic | 0.4592 | ambiguous | -2.322 | Highly Destabilizing | 0.958 | D | 0.769 | deleterious | N | 0.495486974 | None | None | N |
| P/C | 0.9229 | likely_pathogenic | 0.8778 | pathogenic | -2.302 | Highly Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| P/D | 0.9972 | likely_pathogenic | 0.9974 | pathogenic | -3.193 | Highly Destabilizing | 0.998 | D | 0.837 | deleterious | None | None | None | None | N |
| P/E | 0.9879 | likely_pathogenic | 0.9873 | pathogenic | -2.971 | Highly Destabilizing | 0.998 | D | 0.838 | deleterious | None | None | None | None | N |
| P/F | 0.9724 | likely_pathogenic | 0.9695 | pathogenic | -1.326 | Destabilizing | 0.334 | N | 0.653 | neutral | None | None | None | None | N |
| P/G | 0.9589 | likely_pathogenic | 0.9439 | pathogenic | -2.823 | Highly Destabilizing | 0.995 | D | 0.842 | deleterious | None | None | None | None | N |
| P/H | 0.9803 | likely_pathogenic | 0.9791 | pathogenic | -2.417 | Highly Destabilizing | 0.999 | D | 0.861 | deleterious | N | 0.507857237 | None | None | N |
| P/I | 0.6378 | likely_pathogenic | 0.5822 | pathogenic | -0.912 | Destabilizing | 0.982 | D | 0.871 | deleterious | None | None | None | None | N |
| P/K | 0.9912 | likely_pathogenic | 0.9913 | pathogenic | -1.821 | Destabilizing | 0.995 | D | 0.837 | deleterious | None | None | None | None | N |
| P/L | 0.4322 | ambiguous | 0.357 | ambiguous | -0.912 | Destabilizing | 0.976 | D | 0.841 | deleterious | N | 0.512581832 | None | None | N |
| P/M | 0.7958 | likely_pathogenic | 0.7516 | pathogenic | -1.364 | Destabilizing | 0.999 | D | 0.869 | deleterious | None | None | None | None | N |
| P/N | 0.989 | likely_pathogenic | 0.9889 | pathogenic | -2.252 | Highly Destabilizing | 0.998 | D | 0.875 | deleterious | None | None | None | None | N |
| P/Q | 0.9653 | likely_pathogenic | 0.9607 | pathogenic | -2.104 | Highly Destabilizing | 0.998 | D | 0.837 | deleterious | None | None | None | None | N |
| P/R | 0.9812 | likely_pathogenic | 0.9806 | pathogenic | -1.67 | Destabilizing | 0.998 | D | 0.881 | deleterious | D | 0.537317798 | None | None | N |
| P/S | 0.9344 | likely_pathogenic | 0.9147 | pathogenic | -2.813 | Highly Destabilizing | 0.994 | D | 0.836 | deleterious | D | 0.537064308 | None | None | N |
| P/T | 0.787 | likely_pathogenic | 0.7378 | pathogenic | -2.453 | Highly Destabilizing | 0.994 | D | 0.847 | deleterious | N | 0.510312773 | None | None | N |
| P/V | 0.5074 | ambiguous | 0.4512 | ambiguous | -1.359 | Destabilizing | 0.991 | D | 0.857 | deleterious | None | None | None | None | N |
| P/W | 0.9936 | likely_pathogenic | 0.993 | pathogenic | -1.747 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| P/Y | 0.9854 | likely_pathogenic | 0.9834 | pathogenic | -1.459 | Destabilizing | 0.982 | D | 0.868 | 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.