Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17727 | 53404;53405;53406 | chr2:178607509;178607508;178607507 | chr2:179472236;179472235;179472234 |
| N2AB | 16086 | 48481;48482;48483 | chr2:178607509;178607508;178607507 | chr2:179472236;179472235;179472234 |
| N2A | 15159 | 45700;45701;45702 | chr2:178607509;178607508;178607507 | chr2:179472236;179472235;179472234 |
| N2B | 8662 | 26209;26210;26211 | chr2:178607509;178607508;178607507 | chr2:179472236;179472235;179472234 |
| Novex-1 | 8787 | 26584;26585;26586 | chr2:178607509;178607508;178607507 | chr2:179472236;179472235;179472234 |
| Novex-2 | 8854 | 26785;26786;26787 | chr2:178607509;178607508;178607507 | chr2:179472236;179472235;179472234 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs369262757  |
-0.463 | 1.0 | N | 0.749 | 0.376 | None | gnomAD-2.1.1 | 3.57E-05 | None | None | None | None | N | None | 0 | 0 | None | 8.69733E-04 | 0 | None | 0 | None | 0 | 7.82E-06 | 0 |
| S/C | rs369262757 |
-0.463 | 1.0 | N | 0.749 | 0.376 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 1.15207E-03 | 1.94628E-04 | None | 0 | 0 | 0 | 0 | 0 |
| S/C | rs369262757 |
-0.463 | 1.0 | N | 0.749 | 0.376 | None | gnomAD-4.0.0 | 1.61167E-05 | None | None | None | None | N | None | 0 | 0 | None | 7.09795E-04 | 2.23155E-05 | None | 0 | 0 | 1.69581E-06 | 0 | 3.20287E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2024 | likely_benign | 0.2343 | benign | -0.691 | Destabilizing | 0.973 | D | 0.589 | neutral | N | 0.509637527 | None | None | N |
| S/C | 0.1572 | likely_benign | 0.169 | benign | -0.687 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.464948506 | None | None | N |
| S/D | 0.9099 | likely_pathogenic | 0.9239 | pathogenic | -1.827 | Destabilizing | 0.996 | D | 0.668 | neutral | None | None | None | None | N |
| S/E | 0.9517 | likely_pathogenic | 0.9603 | pathogenic | -1.619 | Destabilizing | 0.996 | D | 0.659 | neutral | None | None | None | None | N |
| S/F | 0.8641 | likely_pathogenic | 0.9013 | pathogenic | -0.544 | Destabilizing | 0.999 | D | 0.781 | deleterious | N | 0.47831582 | None | None | N |
| S/G | 0.335 | likely_benign | 0.4319 | ambiguous | -1.088 | Destabilizing | 0.996 | D | 0.621 | neutral | None | None | None | None | N |
| S/H | 0.866 | likely_pathogenic | 0.8899 | pathogenic | -1.57 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| S/I | 0.607 | likely_pathogenic | 0.6993 | pathogenic | 0.315 | Stabilizing | 0.998 | D | 0.781 | deleterious | None | None | None | None | N |
| S/K | 0.994 | likely_pathogenic | 0.9967 | pathogenic | -0.31 | Destabilizing | 0.996 | D | 0.663 | neutral | None | None | None | None | N |
| S/L | 0.4919 | ambiguous | 0.6151 | pathogenic | 0.315 | Stabilizing | 0.992 | D | 0.704 | prob.neutral | None | None | None | None | N |
| S/M | 0.5333 | ambiguous | 0.5995 | pathogenic | 0.191 | Stabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| S/N | 0.5094 | ambiguous | 0.605 | pathogenic | -1.158 | Destabilizing | 0.996 | D | 0.663 | neutral | None | None | None | None | N |
| S/P | 0.9855 | likely_pathogenic | 0.9931 | pathogenic | 0.015 | Stabilizing | 0.999 | D | 0.741 | deleterious | N | 0.510057786 | None | None | N |
| S/Q | 0.935 | likely_pathogenic | 0.9533 | pathogenic | -0.84 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| S/R | 0.9874 | likely_pathogenic | 0.9928 | pathogenic | -0.801 | Destabilizing | 0.999 | D | 0.751 | deleterious | None | None | None | None | N |
| S/T | 0.1257 | likely_benign | 0.1433 | benign | -0.697 | Destabilizing | 0.543 | D | 0.529 | neutral | N | 0.492745277 | None | None | N |
| S/V | 0.5061 | ambiguous | 0.5715 | pathogenic | 0.015 | Stabilizing | 0.998 | D | 0.746 | deleterious | None | None | None | None | N |
| S/W | 0.8269 | likely_pathogenic | 0.8705 | pathogenic | -0.938 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| S/Y | 0.7141 | likely_pathogenic | 0.7878 | pathogenic | -0.442 | Destabilizing | 0.999 | D | 0.785 | deleterious | N | 0.455945604 | 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.