Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15015 | 45268;45269;45270 | chr2:178621879;178621878;178621877 | chr2:179486606;179486605;179486604 |
| N2AB | 13374 | 40345;40346;40347 | chr2:178621879;178621878;178621877 | chr2:179486606;179486605;179486604 |
| N2A | 12447 | 37564;37565;37566 | chr2:178621879;178621878;178621877 | chr2:179486606;179486605;179486604 |
| N2B | 5950 | 18073;18074;18075 | chr2:178621879;178621878;178621877 | chr2:179486606;179486605;179486604 |
| Novex-1 | 6075 | 18448;18449;18450 | chr2:178621879;178621878;178621877 | chr2:179486606;179486605;179486604 |
| Novex-2 | 6142 | 18649;18650;18651 | chr2:178621879;178621878;178621877 | chr2:179486606;179486605;179486604 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/E | rs786205390  |
None | 0.642 | D | 0.699 | 0.614 | 0.669984208518 | gnomAD-4.0.0 | 1.98609E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.84029E-04 | None | 0 | 0 | 0 | 0 | 3.31807E-05 |
| V/I | rs1280583303 |
-0.529 | 0.425 | D | 0.565 | 0.207 | 0.467074840246 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| V/I | rs1280583303 |
-0.529 | 0.425 | D | 0.565 | 0.207 | 0.467074840246 | gnomAD-4.0.0 | 1.59476E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86392E-06 | 0 | 0 |
| V/L | None | None | 0.425 | D | 0.421 | 0.283 | 0.491112125781 | gnomAD-4.0.0 | 1.59476E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86392E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2318 | likely_benign | 0.2019 | benign | -1.697 | Destabilizing | 0.001 | N | 0.255 | neutral | N | 0.381849952 | None | None | N |
| V/C | 0.864 | likely_pathogenic | 0.8366 | pathogenic | -1.161 | Destabilizing | 0.944 | D | 0.756 | deleterious | None | None | None | None | N |
| V/D | 0.6943 | likely_pathogenic | 0.6713 | pathogenic | -1.658 | Destabilizing | 0.704 | D | 0.747 | deleterious | None | None | None | None | N |
| V/E | 0.7133 | likely_pathogenic | 0.7071 | pathogenic | -1.566 | Destabilizing | 0.642 | D | 0.699 | prob.neutral | D | 0.648629122 | None | None | N |
| V/F | 0.478 | ambiguous | 0.4469 | ambiguous | -1.098 | Destabilizing | 0.944 | D | 0.767 | deleterious | None | None | None | None | N |
| V/G | 0.3026 | likely_benign | 0.2728 | benign | -2.127 | Highly Destabilizing | 0.27 | N | 0.634 | neutral | D | 0.584681827 | None | None | N |
| V/H | 0.91 | likely_pathogenic | 0.9108 | pathogenic | -1.799 | Destabilizing | 0.981 | D | 0.791 | deleterious | None | None | None | None | N |
| V/I | 0.1343 | likely_benign | 0.1439 | benign | -0.569 | Destabilizing | 0.425 | N | 0.565 | neutral | D | 0.522970719 | None | None | N |
| V/K | 0.8677 | likely_pathogenic | 0.8779 | pathogenic | -1.447 | Destabilizing | 0.704 | D | 0.704 | prob.neutral | None | None | None | None | N |
| V/L | 0.4362 | ambiguous | 0.4611 | ambiguous | -0.569 | Destabilizing | 0.425 | N | 0.421 | neutral | D | 0.522671838 | None | None | N |
| V/M | 0.3892 | ambiguous | 0.3847 | ambiguous | -0.474 | Destabilizing | 0.981 | D | 0.665 | neutral | None | None | None | None | N |
| V/N | 0.5884 | likely_pathogenic | 0.5835 | pathogenic | -1.367 | Destabilizing | 0.704 | D | 0.768 | deleterious | None | None | None | None | N |
| V/P | 0.9253 | likely_pathogenic | 0.9358 | pathogenic | -0.912 | Destabilizing | 0.828 | D | 0.741 | deleterious | None | None | None | None | N |
| V/Q | 0.8143 | likely_pathogenic | 0.8243 | pathogenic | -1.39 | Destabilizing | 0.944 | D | 0.787 | deleterious | None | None | None | None | N |
| V/R | 0.8335 | likely_pathogenic | 0.8431 | pathogenic | -1.106 | Destabilizing | 0.893 | D | 0.793 | deleterious | None | None | None | None | N |
| V/S | 0.32 | likely_benign | 0.2886 | benign | -1.965 | Destabilizing | 0.013 | N | 0.472 | neutral | None | None | None | None | N |
| V/T | 0.3175 | likely_benign | 0.2728 | benign | -1.744 | Destabilizing | 0.329 | N | 0.533 | neutral | None | None | None | None | N |
| V/W | 0.9677 | likely_pathogenic | 0.9665 | pathogenic | -1.44 | Destabilizing | 0.995 | D | 0.773 | deleterious | None | None | None | None | N |
| V/Y | 0.8428 | likely_pathogenic | 0.8422 | pathogenic | -1.1 | Destabilizing | 0.981 | D | 0.771 | 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.