Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35374 | 106345;106346;106347 | chr2:178530495;178530494;178530493 | chr2:179395222;179395221;179395220 |
| N2AB | 33733 | 101422;101423;101424 | chr2:178530495;178530494;178530493 | chr2:179395222;179395221;179395220 |
| N2A | 32806 | 98641;98642;98643 | chr2:178530495;178530494;178530493 | chr2:179395222;179395221;179395220 |
| N2B | 26309 | 79150;79151;79152 | chr2:178530495;178530494;178530493 | chr2:179395222;179395221;179395220 |
| Novex-1 | 26434 | 79525;79526;79527 | chr2:178530495;178530494;178530493 | chr2:179395222;179395221;179395220 |
| Novex-2 | 26501 | 79726;79727;79728 | chr2:178530495;178530494;178530493 | chr2:179395222;179395221;179395220 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/Y | rs727504609  |
-0.364 | 0.997 | N | 0.611 | 0.27 | None | gnomAD-2.1.1 | 1.92578E-04 | None | None | None | None | N | None | 0 | 0 | None | 4.63499E-03 | 0 | None | 0 | None | 0 | 3.12E-05 | 2.8082E-04 |
| F/Y | rs727504609 |
-0.364 | 0.997 | N | 0.611 | 0.27 | None | gnomAD-3.1.2 | 1.05184E-04 | None | None | None | None | N | None | 0 | 0 | 0 | 4.03458E-03 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| F/Y | rs727504609 |
-0.364 | 0.997 | N | 0.611 | 0.27 | None | gnomAD-4.0.0 | 1.11539E-04 | None | None | None | None | N | None | 0 | 0 | None | 5.10066E-03 | 0 | None | 0 | 0 | 1.52557E-05 | 0 | 1.7609E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.973 | likely_pathogenic | 0.9679 | pathogenic | -2.434 | Highly Destabilizing | 0.985 | D | 0.675 | neutral | None | None | None | None | N |
| F/C | 0.8817 | likely_pathogenic | 0.8822 | pathogenic | -1.889 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | N | 0.437533455 | None | None | N |
| F/D | 0.9942 | likely_pathogenic | 0.9925 | pathogenic | -1.476 | Destabilizing | 0.998 | D | 0.739 | prob.delet. | None | None | None | None | N |
| F/E | 0.9933 | likely_pathogenic | 0.9916 | pathogenic | -1.322 | Destabilizing | 0.998 | D | 0.723 | prob.delet. | None | None | None | None | N |
| F/G | 0.9833 | likely_pathogenic | 0.9801 | pathogenic | -2.82 | Highly Destabilizing | 0.998 | D | 0.713 | prob.delet. | None | None | None | None | N |
| F/H | 0.9665 | likely_pathogenic | 0.9639 | pathogenic | -1.087 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| F/I | 0.5541 | ambiguous | 0.4237 | ambiguous | -1.232 | Destabilizing | 0.961 | D | 0.635 | neutral | N | 0.451519438 | None | None | N |
| F/K | 0.993 | likely_pathogenic | 0.9915 | pathogenic | -1.912 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | None | None | None | None | N |
| F/L | 0.9358 | likely_pathogenic | 0.9274 | pathogenic | -1.232 | Destabilizing | 0.135 | N | 0.329 | neutral | N | 0.371415498 | None | None | N |
| F/M | 0.8508 | likely_pathogenic | 0.8414 | pathogenic | -1.141 | Destabilizing | 0.996 | D | 0.678 | prob.neutral | None | None | None | None | N |
| F/N | 0.9828 | likely_pathogenic | 0.9792 | pathogenic | -2.176 | Highly Destabilizing | 0.998 | D | 0.741 | deleterious | None | None | None | None | N |
| F/P | 0.9987 | likely_pathogenic | 0.998 | pathogenic | -1.633 | Destabilizing | 0.999 | D | 0.748 | deleterious | None | None | None | None | N |
| F/Q | 0.9902 | likely_pathogenic | 0.9887 | pathogenic | -2.106 | Highly Destabilizing | 0.999 | D | 0.749 | deleterious | None | None | None | None | N |
| F/R | 0.9852 | likely_pathogenic | 0.9829 | pathogenic | -1.39 | Destabilizing | 0.998 | D | 0.751 | deleterious | None | None | None | None | N |
| F/S | 0.9769 | likely_pathogenic | 0.972 | pathogenic | -2.988 | Highly Destabilizing | 0.961 | D | 0.677 | prob.neutral | N | 0.437026476 | None | None | N |
| F/T | 0.9789 | likely_pathogenic | 0.9739 | pathogenic | -2.72 | Highly Destabilizing | 0.469 | N | 0.538 | neutral | None | None | None | None | N |
| F/V | 0.6504 | likely_pathogenic | 0.6217 | pathogenic | -1.633 | Destabilizing | 0.961 | D | 0.652 | neutral | N | 0.432912248 | None | None | N |
| F/W | 0.7854 | likely_pathogenic | 0.7853 | pathogenic | -0.329 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| F/Y | 0.4056 | ambiguous | 0.4017 | ambiguous | -0.695 | Destabilizing | 0.997 | D | 0.611 | neutral | N | 0.437026476 | 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.