Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28724 | 86395;86396;86397 | chr2:178559962;178559961;178559960 | chr2:179424689;179424688;179424687 |
| N2AB | 27083 | 81472;81473;81474 | chr2:178559962;178559961;178559960 | chr2:179424689;179424688;179424687 |
| N2A | 26156 | 78691;78692;78693 | chr2:178559962;178559961;178559960 | chr2:179424689;179424688;179424687 |
| N2B | 19659 | 59200;59201;59202 | chr2:178559962;178559961;178559960 | chr2:179424689;179424688;179424687 |
| Novex-1 | 19784 | 59575;59576;59577 | chr2:178559962;178559961;178559960 | chr2:179424689;179424688;179424687 |
| Novex-2 | 19851 | 59776;59777;59778 | chr2:178559962;178559961;178559960 | chr2:179424689;179424688;179424687 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | None | None | 0.309 | N | 0.527 | 0.217 | 0.227934060464 | gnomAD-4.0.0 | 1.59133E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8582E-06 | 0 | 0 |
| R/S | rs1288068048  |
-2.247 | 0.521 | N | 0.521 | 0.321 | 0.284150004643 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/S | rs1288068048 |
-2.247 | 0.521 | N | 0.521 | 0.321 | 0.284150004643 | gnomAD-4.0.0 | 4.77394E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.29824E-05 | 0 |
| R/T | rs753277107 |
-1.788 | 0.684 | N | 0.529 | 0.316 | 0.49676076625 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7464 | likely_pathogenic | 0.6312 | pathogenic | -2.004 | Highly Destabilizing | 0.373 | N | 0.513 | neutral | None | None | None | None | N |
| R/C | 0.1894 | likely_benign | 0.1529 | benign | -1.951 | Destabilizing | 0.996 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/D | 0.9821 | likely_pathogenic | 0.9641 | pathogenic | -0.981 | Destabilizing | 0.742 | D | 0.531 | neutral | None | None | None | None | N |
| R/E | 0.8149 | likely_pathogenic | 0.7156 | pathogenic | -0.762 | Destabilizing | 0.373 | N | 0.533 | neutral | None | None | None | None | N |
| R/F | 0.899 | likely_pathogenic | 0.827 | pathogenic | -1.221 | Destabilizing | 0.953 | D | 0.648 | neutral | None | None | None | None | N |
| R/G | 0.7965 | likely_pathogenic | 0.6739 | pathogenic | -2.347 | Highly Destabilizing | 0.684 | D | 0.541 | neutral | D | 0.536702822 | None | None | N |
| R/H | 0.2278 | likely_benign | 0.176 | benign | -2.195 | Highly Destabilizing | 0.953 | D | 0.534 | neutral | None | None | None | None | N |
| R/I | 0.5772 | likely_pathogenic | 0.4723 | ambiguous | -1.006 | Destabilizing | 0.521 | D | 0.563 | neutral | N | 0.492100521 | None | None | N |
| R/K | 0.2303 | likely_benign | 0.2007 | benign | -1.385 | Destabilizing | 0.309 | N | 0.527 | neutral | N | 0.481576682 | None | None | N |
| R/L | 0.5889 | likely_pathogenic | 0.4643 | ambiguous | -1.006 | Destabilizing | 0.373 | N | 0.549 | neutral | None | None | None | None | N |
| R/M | 0.6357 | likely_pathogenic | 0.515 | ambiguous | -1.537 | Destabilizing | 0.953 | D | 0.607 | neutral | None | None | None | None | N |
| R/N | 0.9191 | likely_pathogenic | 0.8552 | pathogenic | -1.369 | Destabilizing | 0.742 | D | 0.512 | neutral | None | None | None | None | N |
| R/P | 0.9957 | likely_pathogenic | 0.9945 | pathogenic | -1.328 | Destabilizing | 0.953 | D | 0.613 | neutral | None | None | None | None | N |
| R/Q | 0.1592 | likely_benign | 0.1333 | benign | -1.222 | Destabilizing | 0.016 | N | 0.279 | neutral | None | None | None | None | N |
| R/S | 0.8211 | likely_pathogenic | 0.7168 | pathogenic | -2.257 | Highly Destabilizing | 0.521 | D | 0.521 | neutral | N | 0.481069703 | None | None | N |
| R/T | 0.6786 | likely_pathogenic | 0.5099 | ambiguous | -1.825 | Destabilizing | 0.684 | D | 0.529 | neutral | N | 0.475575974 | None | None | N |
| R/V | 0.5921 | likely_pathogenic | 0.5137 | ambiguous | -1.328 | Destabilizing | 0.016 | N | 0.578 | neutral | None | None | None | None | N |
| R/W | 0.5497 | ambiguous | 0.4533 | ambiguous | -0.741 | Destabilizing | 0.996 | D | 0.719 | prob.delet. | None | None | None | None | N |
| R/Y | 0.7985 | likely_pathogenic | 0.6818 | pathogenic | -0.599 | Destabilizing | 0.953 | D | 0.632 | 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.