Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20639 | 62140;62141;62142 | chr2:178589810;178589809;178589808 | chr2:179454537;179454536;179454535 |
| N2AB | 18998 | 57217;57218;57219 | chr2:178589810;178589809;178589808 | chr2:179454537;179454536;179454535 |
| N2A | 18071 | 54436;54437;54438 | chr2:178589810;178589809;178589808 | chr2:179454537;179454536;179454535 |
| N2B | 11574 | 34945;34946;34947 | chr2:178589810;178589809;178589808 | chr2:179454537;179454536;179454535 |
| Novex-1 | 11699 | 35320;35321;35322 | chr2:178589810;178589809;178589808 | chr2:179454537;179454536;179454535 |
| Novex-2 | 11766 | 35521;35522;35523 | chr2:178589810;178589809;178589808 | chr2:179454537;179454536;179454535 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs756303390  |
-1.332 | 0.978 | N | 0.601 | 0.355 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 1.23987E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/C | rs756303390 |
-1.332 | 0.978 | N | 0.601 | 0.355 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 9.65E-05 | 1.96464E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/C | rs756303390 |
-1.332 | 0.978 | N | 0.601 | 0.355 | None | gnomAD-4.0.0 | 1.36356E-05 | None | None | None | None | N | None | 8.01111E-05 | 5.00167E-05 | None | 0 | 0 | None | 0 | 0 | 9.3251E-06 | 0 | 3.20287E-05 |
| Y/H | rs727503587 |
-2.522 | 0.921 | N | 0.535 | 0.195 | None | gnomAD-2.1.1 | 7.13E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| Y/H | rs727503587 |
-2.522 | 0.921 | N | 0.535 | 0.195 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| Y/H | rs727503587 |
-2.522 | 0.921 | N | 0.535 | 0.195 | None | gnomAD-4.0.0 | 1.02519E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.9152E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.7817 | likely_pathogenic | 0.7332 | pathogenic | -2.929 | Highly Destabilizing | 0.228 | N | 0.552 | neutral | None | None | None | None | N |
| Y/C | 0.2562 | likely_benign | 0.2086 | benign | -1.168 | Destabilizing | 0.978 | D | 0.601 | neutral | N | 0.500202472 | None | None | N |
| Y/D | 0.8638 | likely_pathogenic | 0.7952 | pathogenic | -2.918 | Highly Destabilizing | 0.921 | D | 0.63 | neutral | N | 0.451197804 | None | None | N |
| Y/E | 0.9412 | likely_pathogenic | 0.9077 | pathogenic | -2.733 | Highly Destabilizing | 0.816 | D | 0.619 | neutral | None | None | None | None | N |
| Y/F | 0.0695 | likely_benign | 0.0577 | benign | -1.021 | Destabilizing | None | N | 0.237 | neutral | N | 0.414199641 | None | None | N |
| Y/G | 0.8144 | likely_pathogenic | 0.7824 | pathogenic | -3.298 | Highly Destabilizing | 0.593 | D | 0.553 | neutral | None | None | None | None | N |
| Y/H | 0.3597 | ambiguous | 0.2952 | benign | -1.822 | Destabilizing | 0.921 | D | 0.535 | neutral | N | 0.462068159 | None | None | N |
| Y/I | 0.5031 | ambiguous | 0.4536 | ambiguous | -1.708 | Destabilizing | 0.129 | N | 0.514 | neutral | None | None | None | None | N |
| Y/K | 0.8932 | likely_pathogenic | 0.8142 | pathogenic | -1.647 | Destabilizing | 0.593 | D | 0.601 | neutral | None | None | None | None | N |
| Y/L | 0.4271 | ambiguous | 0.3795 | ambiguous | -1.708 | Destabilizing | None | N | 0.362 | neutral | None | None | None | None | N |
| Y/M | 0.6385 | likely_pathogenic | 0.5734 | pathogenic | -1.327 | Destabilizing | 0.716 | D | 0.563 | neutral | None | None | None | None | N |
| Y/N | 0.5143 | ambiguous | 0.4504 | ambiguous | -2.264 | Highly Destabilizing | 0.921 | D | 0.61 | neutral | N | 0.43087846 | None | None | N |
| Y/P | 0.9967 | likely_pathogenic | 0.9936 | pathogenic | -2.128 | Highly Destabilizing | 0.94 | D | 0.609 | neutral | None | None | None | None | N |
| Y/Q | 0.8098 | likely_pathogenic | 0.7303 | pathogenic | -2.105 | Highly Destabilizing | 0.94 | D | 0.564 | neutral | None | None | None | None | N |
| Y/R | 0.7833 | likely_pathogenic | 0.6795 | pathogenic | -1.358 | Destabilizing | 0.836 | D | 0.626 | neutral | None | None | None | None | N |
| Y/S | 0.4838 | ambiguous | 0.4334 | ambiguous | -2.634 | Highly Destabilizing | 0.523 | D | 0.575 | neutral | N | 0.431782537 | None | None | N |
| Y/T | 0.6724 | likely_pathogenic | 0.619 | pathogenic | -2.347 | Highly Destabilizing | 0.593 | D | 0.588 | neutral | None | None | None | None | N |
| Y/V | 0.4723 | ambiguous | 0.4198 | ambiguous | -2.128 | Highly Destabilizing | 0.129 | N | 0.466 | neutral | None | None | None | None | N |
| Y/W | 0.5492 | ambiguous | 0.4804 | ambiguous | -0.303 | Destabilizing | 0.94 | D | 0.555 | 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.