Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29607 | 89044;89045;89046 | chr2:178554528;178554527;178554526 | chr2:179419255;179419254;179419253 |
| N2AB | 27966 | 84121;84122;84123 | chr2:178554528;178554527;178554526 | chr2:179419255;179419254;179419253 |
| N2A | 27039 | 81340;81341;81342 | chr2:178554528;178554527;178554526 | chr2:179419255;179419254;179419253 |
| N2B | 20542 | 61849;61850;61851 | chr2:178554528;178554527;178554526 | chr2:179419255;179419254;179419253 |
| Novex-1 | 20667 | 62224;62225;62226 | chr2:178554528;178554527;178554526 | chr2:179419255;179419254;179419253 |
| Novex-2 | 20734 | 62425;62426;62427 | chr2:178554528;178554527;178554526 | chr2:179419255;179419254;179419253 |
| 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/G | rs781330566  |
-2.365 | 0.996 | D | 0.562 | 0.488 | 0.63986833561 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/G | rs781330566 |
-2.365 | 0.996 | D | 0.562 | 0.488 | 0.63986833561 | gnomAD-4.0.0 | 1.36873E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79892E-06 | 0 | 0 |
| R/Q | rs755212831 |
-1.138 | 0.884 | N | 0.498 | 0.424 | 0.366085729538 | gnomAD-2.1.1 | 4.84E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.26883E-04 | None | 0 | 1.78E-05 | 0 |
| R/Q | rs755212831 |
-1.138 | 0.884 | N | 0.498 | 0.424 | 0.366085729538 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 2.07383E-04 | 0 |
| R/Q | rs755212831 |
-1.138 | 0.884 | N | 0.498 | 0.424 | 0.366085729538 | gnomAD-4.0.0 | 3.28474E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23364E-05 | None | 0 | 0 | 9.32347E-06 | 4.39252E-04 | 1.60164E-05 |
| R/W | rs781330566 |
-0.729 | 1.0 | D | 0.73 | 0.486 | 0.764626318615 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 4.14E-05 | 5.67E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.84E-06 | 0 |
| R/W | rs781330566 |
-0.729 | 1.0 | D | 0.73 | 0.486 | 0.764626318615 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 7.25E-05 | 0 | 0 | 0 | 3.85356E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/W | rs781330566 |
-0.729 | 1.0 | D | 0.73 | 0.486 | 0.764626318615 | gnomAD-4.0.0 | 1.17765E-05 | None | None | None | None | N | None | 4.00053E-05 | 3.33522E-05 | None | 0 | 4.46867E-05 | None | 0 | 0 | 4.23811E-06 | 1.09832E-05 | 9.61046E-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 | 0.9741 | likely_pathogenic | 0.9766 | pathogenic | -1.852 | Destabilizing | 0.983 | D | 0.525 | neutral | None | None | None | None | N |
| R/C | 0.6158 | likely_pathogenic | 0.6192 | pathogenic | -1.764 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| R/D | 0.9976 | likely_pathogenic | 0.9976 | pathogenic | -1.169 | Destabilizing | 0.995 | D | 0.594 | neutral | None | None | None | None | N |
| R/E | 0.9688 | likely_pathogenic | 0.9696 | pathogenic | -0.958 | Destabilizing | 0.967 | D | 0.557 | neutral | None | None | None | None | N |
| R/F | 0.9905 | likely_pathogenic | 0.9902 | pathogenic | -0.889 | Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | N |
| R/G | 0.966 | likely_pathogenic | 0.9706 | pathogenic | -2.162 | Highly Destabilizing | 0.996 | D | 0.562 | neutral | D | 0.546084118 | None | None | N |
| R/H | 0.5058 | ambiguous | 0.481 | ambiguous | -2.118 | Highly Destabilizing | 0.998 | D | 0.595 | neutral | None | None | None | None | N |
| R/I | 0.9616 | likely_pathogenic | 0.9606 | pathogenic | -0.943 | Destabilizing | 0.998 | D | 0.765 | deleterious | None | None | None | None | N |
| R/K | 0.5343 | ambiguous | 0.5474 | ambiguous | -1.332 | Destabilizing | 0.923 | D | 0.595 | neutral | None | None | None | None | N |
| R/L | 0.9246 | likely_pathogenic | 0.9274 | pathogenic | -0.943 | Destabilizing | 0.991 | D | 0.562 | neutral | N | 0.508318672 | None | None | N |
| R/M | 0.9642 | likely_pathogenic | 0.9648 | pathogenic | -1.496 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| R/N | 0.9903 | likely_pathogenic | 0.9905 | pathogenic | -1.455 | Destabilizing | 0.995 | D | 0.549 | neutral | None | None | None | None | N |
| R/P | 0.9992 | likely_pathogenic | 0.9991 | pathogenic | -1.237 | Destabilizing | 0.999 | D | 0.663 | neutral | D | 0.546591097 | None | None | N |
| R/Q | 0.4763 | ambiguous | 0.4798 | ambiguous | -1.142 | Destabilizing | 0.884 | D | 0.498 | neutral | N | 0.504556009 | None | None | N |
| R/S | 0.9789 | likely_pathogenic | 0.981 | pathogenic | -2.122 | Highly Destabilizing | 0.983 | D | 0.526 | neutral | None | None | None | None | N |
| R/T | 0.9708 | likely_pathogenic | 0.9728 | pathogenic | -1.722 | Destabilizing | 0.998 | D | 0.537 | neutral | None | None | None | None | N |
| R/V | 0.9673 | likely_pathogenic | 0.9672 | pathogenic | -1.237 | Destabilizing | 0.998 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/W | 0.8453 | likely_pathogenic | 0.8482 | pathogenic | -0.598 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | D | 0.528233353 | None | None | N |
| R/Y | 0.9683 | likely_pathogenic | 0.9686 | pathogenic | -0.479 | Destabilizing | 0.999 | D | 0.715 | prob.delet. | 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.