Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33432 | 100519;100520;100521 | chr2:178536453;178536452;178536451 | chr2:179401180;179401179;179401178 |
| N2AB | 31791 | 95596;95597;95598 | chr2:178536453;178536452;178536451 | chr2:179401180;179401179;179401178 |
| N2A | 30864 | 92815;92816;92817 | chr2:178536453;178536452;178536451 | chr2:179401180;179401179;179401178 |
| N2B | 24367 | 73324;73325;73326 | chr2:178536453;178536452;178536451 | chr2:179401180;179401179;179401178 |
| Novex-1 | 24492 | 73699;73700;73701 | chr2:178536453;178536452;178536451 | chr2:179401180;179401179;179401178 |
| Novex-2 | 24559 | 73900;73901;73902 | chr2:178536453;178536452;178536451 | chr2:179401180;179401179;179401178 |
| 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/C | rs878882035  |
None | 1.0 | D | 0.87 | 0.431 | 0.630346058385 | gnomAD-4.0.0 | 3.20381E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87778E-06 | 1.4445E-05 | 0 |
| R/G | None | None | 1.0 | N | 0.798 | 0.526 | 0.636843794314 | gnomAD-4.0.0 | 1.60191E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.4445E-05 | 0 |
| R/H | rs374876608 |
-2.17 | 1.0 | N | 0.742 | 0.437 | None | gnomAD-2.1.1 | 5.76E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.53941E-04 | None | 2.98567E-04 | None | 0 | 2.37E-05 | 1.41884E-04 |
| R/H | rs374876608 |
-2.17 | 1.0 | N | 0.742 | 0.437 | None | gnomAD-3.1.2 | 1.70814E-04 | None | None | None | None | N | None | 0 | 0 | 2.30263E-02 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| R/H | rs374876608 |
-2.17 | 1.0 | N | 0.742 | 0.437 | None | gnomAD-4.0.0 | 5.65062E-05 | None | None | None | None | N | None | 2.67544E-05 | 3.34672E-05 | None | 0 | 6.68598E-05 | None | 0 | 1.64853E-04 | 3.14121E-05 | 2.64696E-04 | 1.60503E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9215 | likely_pathogenic | 0.9047 | pathogenic | -2.083 | Highly Destabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | N |
| R/C | 0.3593 | ambiguous | 0.3459 | ambiguous | -1.965 | Destabilizing | 1.0 | D | 0.87 | deleterious | D | 0.524447556 | None | None | N |
| R/D | 0.9925 | likely_pathogenic | 0.9917 | pathogenic | -1.153 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| R/E | 0.901 | likely_pathogenic | 0.8879 | pathogenic | -0.919 | Destabilizing | 0.999 | D | 0.621 | neutral | None | None | None | None | N |
| R/F | 0.9379 | likely_pathogenic | 0.9287 | pathogenic | -1.168 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| R/G | 0.8767 | likely_pathogenic | 0.8558 | pathogenic | -2.442 | Highly Destabilizing | 1.0 | D | 0.798 | deleterious | N | 0.490869072 | None | None | N |
| R/H | 0.3864 | ambiguous | 0.3418 | ambiguous | -2.155 | Highly Destabilizing | 1.0 | D | 0.742 | deleterious | N | 0.470309282 | None | None | N |
| R/I | 0.7932 | likely_pathogenic | 0.791 | pathogenic | -1.03 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| R/K | 0.2028 | likely_benign | 0.1707 | benign | -1.313 | Destabilizing | 0.998 | D | 0.447 | neutral | None | None | None | None | N |
| R/L | 0.7279 | likely_pathogenic | 0.7153 | pathogenic | -1.03 | Destabilizing | 1.0 | D | 0.798 | deleterious | N | 0.473156438 | None | None | N |
| R/M | 0.7355 | likely_pathogenic | 0.704 | pathogenic | -1.54 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| R/N | 0.9662 | likely_pathogenic | 0.9607 | pathogenic | -1.481 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/P | 0.9978 | likely_pathogenic | 0.9978 | pathogenic | -1.371 | Destabilizing | 1.0 | D | 0.867 | deleterious | N | 0.517620608 | None | None | N |
| R/Q | 0.263 | likely_benign | 0.234 | benign | -1.277 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| R/S | 0.9666 | likely_pathogenic | 0.9597 | pathogenic | -2.355 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | N | 0.510072749 | None | None | N |
| R/T | 0.8957 | likely_pathogenic | 0.8835 | pathogenic | -1.898 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| R/V | 0.8608 | likely_pathogenic | 0.8456 | pathogenic | -1.371 | Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | N |
| R/W | 0.6595 | likely_pathogenic | 0.6393 | pathogenic | -0.682 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| R/Y | 0.8448 | likely_pathogenic | 0.8282 | pathogenic | -0.576 | Destabilizing | 1.0 | D | 0.882 | 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.