Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21996 | 66211;66212;66213 | chr2:178582470;178582469;178582468 | chr2:179447197;179447196;179447195 |
| N2AB | 20355 | 61288;61289;61290 | chr2:178582470;178582469;178582468 | chr2:179447197;179447196;179447195 |
| N2A | 19428 | 58507;58508;58509 | chr2:178582470;178582469;178582468 | chr2:179447197;179447196;179447195 |
| N2B | 12931 | 39016;39017;39018 | chr2:178582470;178582469;178582468 | chr2:179447197;179447196;179447195 |
| Novex-1 | 13056 | 39391;39392;39393 | chr2:178582470;178582469;178582468 | chr2:179447197;179447196;179447195 |
| Novex-2 | 13123 | 39592;39593;39594 | chr2:178582470;178582469;178582468 | chr2:179447197;179447196;179447195 |
| 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 | rs577114038  |
-1.705 | 0.252 | N | 0.468 | 0.369 | None | gnomAD-2.1.1 | 1.07438E-04 | None | None | None | None | N | None | 4.14E-05 | 5.67247E-04 | None | 0 | 0 | None | 0 | None | 0 | 6.27E-05 | 1.40885E-04 |
| R/C | rs577114038 |
-1.705 | 0.252 | N | 0.468 | 0.369 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 9.65E-05 | 1.31079E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs577114038 |
-1.705 | 0.252 | N | 0.468 | 0.369 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/C | rs577114038 |
-1.705 | 0.252 | N | 0.468 | 0.369 | None | gnomAD-4.0.0 | 4.89799E-05 | None | None | None | None | N | None | 1.06707E-04 | 4.67025E-04 | None | 0 | 0 | None | 0 | 1.6518E-04 | 3.30693E-05 | 1.09849E-05 | 3.20318E-05 |
| R/H | rs374489349 |
-2.535 | 1.0 | N | 0.533 | 0.469 | None | gnomAD-2.1.1 | 3.58E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.19E-05 | None | 0 | None | 0 | 5.49E-05 | 2.81928E-04 |
| R/H | rs374489349 |
-2.535 | 1.0 | N | 0.533 | 0.469 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| R/H | rs374489349 |
-2.535 | 1.0 | N | 0.533 | 0.469 | None | gnomAD-4.0.0 | 4.58827E-05 | None | None | None | None | N | None | 1.33604E-05 | 1.66839E-05 | None | 0 | 4.47808E-05 | None | 0 | 0 | 5.76585E-05 | 0 | 3.20451E-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 | 0.9925 | likely_pathogenic | 0.9878 | pathogenic | -2.014 | Highly Destabilizing | 0.845 | D | 0.561 | neutral | None | None | None | None | N |
| R/C | 0.7714 | likely_pathogenic | 0.6304 | pathogenic | -1.879 | Destabilizing | 0.252 | N | 0.468 | neutral | N | 0.470549545 | None | None | N |
| R/D | 0.9994 | likely_pathogenic | 0.9993 | pathogenic | -1.048 | Destabilizing | 0.996 | D | 0.766 | deleterious | None | None | None | None | N |
| R/E | 0.9885 | likely_pathogenic | 0.9865 | pathogenic | -0.817 | Destabilizing | 0.985 | D | 0.493 | neutral | None | None | None | None | N |
| R/F | 0.9928 | likely_pathogenic | 0.9895 | pathogenic | -1.112 | Destabilizing | 0.987 | D | 0.818 | deleterious | None | None | None | None | N |
| R/G | 0.9878 | likely_pathogenic | 0.9826 | pathogenic | -2.377 | Highly Destabilizing | 0.977 | D | 0.656 | neutral | N | 0.516873366 | None | None | N |
| R/H | 0.8354 | likely_pathogenic | 0.7442 | pathogenic | -2.058 | Highly Destabilizing | 1.0 | D | 0.533 | neutral | N | 0.50404903 | None | None | N |
| R/I | 0.9844 | likely_pathogenic | 0.9751 | pathogenic | -0.953 | Destabilizing | 0.975 | D | 0.811 | deleterious | None | None | None | None | N |
| R/K | 0.5253 | ambiguous | 0.4505 | ambiguous | -1.242 | Destabilizing | 0.957 | D | 0.501 | neutral | None | None | None | None | N |
| R/L | 0.9561 | likely_pathogenic | 0.9405 | pathogenic | -0.953 | Destabilizing | 0.913 | D | 0.639 | neutral | N | 0.500971157 | None | None | N |
| R/M | 0.9587 | likely_pathogenic | 0.9347 | pathogenic | -1.446 | Destabilizing | 0.999 | D | 0.684 | prob.neutral | None | None | None | None | N |
| R/N | 0.9977 | likely_pathogenic | 0.9966 | pathogenic | -1.368 | Destabilizing | 0.996 | D | 0.515 | neutral | None | None | None | None | N |
| R/P | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -1.297 | Destabilizing | 0.998 | D | 0.778 | deleterious | D | 0.539839466 | None | None | N |
| R/Q | 0.6782 | likely_pathogenic | 0.5753 | pathogenic | -1.197 | Destabilizing | 0.996 | D | 0.526 | neutral | None | None | None | None | N |
| R/S | 0.9977 | likely_pathogenic | 0.9963 | pathogenic | -2.271 | Highly Destabilizing | 0.954 | D | 0.598 | neutral | N | 0.488979287 | None | None | N |
| R/T | 0.994 | likely_pathogenic | 0.991 | pathogenic | -1.819 | Destabilizing | 0.916 | D | 0.61 | neutral | None | None | None | None | N |
| R/V | 0.9833 | likely_pathogenic | 0.9766 | pathogenic | -1.297 | Destabilizing | 0.975 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/W | 0.9303 | likely_pathogenic | 0.9074 | pathogenic | -0.614 | Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | N |
| R/Y | 0.9777 | likely_pathogenic | 0.9667 | pathogenic | -0.499 | Destabilizing | 0.996 | D | 0.785 | 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.