Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19324 | 58195;58196;58197 | chr2:178594524;178594523;178594522 | chr2:179459251;179459250;179459249 |
| N2AB | 17683 | 53272;53273;53274 | chr2:178594524;178594523;178594522 | chr2:179459251;179459250;179459249 |
| N2A | 16756 | 50491;50492;50493 | chr2:178594524;178594523;178594522 | chr2:179459251;179459250;179459249 |
| N2B | 10259 | 31000;31001;31002 | chr2:178594524;178594523;178594522 | chr2:179459251;179459250;179459249 |
| Novex-1 | 10384 | 31375;31376;31377 | chr2:178594524;178594523;178594522 | chr2:179459251;179459250;179459249 |
| Novex-2 | 10451 | 31576;31577;31578 | chr2:178594524;178594523;178594522 | chr2:179459251;179459250;179459249 |
| 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/Q | rs186809500  |
-1.171 | 1.0 | N | 0.689 | 0.515 | None | gnomAD-2.1.1 | 7.24E-05 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 8.37895E-04 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/Q | rs186809500 |
-1.171 | 1.0 | N | 0.689 | 0.515 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 9.73141E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs186809500 |
-1.171 | 1.0 | N | 0.689 | 0.515 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 3E-03 | 0 | None | None | None | 0 | None |
| R/Q | rs186809500 |
-1.171 | 1.0 | N | 0.689 | 0.515 | None | gnomAD-4.0.0 | 2.35542E-05 | None | None | None | None | N | None | 5.33433E-05 | 3.33556E-05 | None | 0 | 4.24486E-04 | None | 0 | 0 | 4.23901E-06 | 1.09844E-05 | 1.12054E-04 |
| R/W | rs1203435642 |
-0.844 | 1.0 | N | 0.887 | 0.601 | 0.695533483703 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/W | rs1203435642 |
-0.844 | 1.0 | N | 0.887 | 0.601 | 0.695533483703 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs1203435642 |
-0.844 | 1.0 | N | 0.887 | 0.601 | 0.695533483703 | gnomAD-4.0.0 | 6.81886E-06 | None | None | None | None | N | None | 0 | 1.66828E-05 | None | 0 | 2.23374E-05 | None | 0 | 0 | 5.93459E-06 | 1.09861E-05 | 1.60128E-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 | 0.9834 | likely_pathogenic | 0.9692 | pathogenic | -1.772 | Destabilizing | 0.999 | D | 0.584 | neutral | None | None | None | None | N |
| R/C | 0.6769 | likely_pathogenic | 0.5362 | ambiguous | -1.83 | Destabilizing | 1.0 | D | 0.904 | deleterious | None | None | None | None | N |
| R/D | 0.9966 | likely_pathogenic | 0.9942 | pathogenic | -0.763 | Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | N |
| R/E | 0.9724 | likely_pathogenic | 0.9508 | pathogenic | -0.596 | Destabilizing | 0.999 | D | 0.565 | neutral | None | None | None | None | N |
| R/F | 0.9893 | likely_pathogenic | 0.9798 | pathogenic | -1.339 | Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| R/G | 0.9772 | likely_pathogenic | 0.9532 | pathogenic | -2.094 | Highly Destabilizing | 1.0 | D | 0.758 | deleterious | N | 0.50271913 | None | None | N |
| R/H | 0.6463 | likely_pathogenic | 0.4794 | ambiguous | -1.977 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| R/I | 0.9627 | likely_pathogenic | 0.9423 | pathogenic | -0.865 | Destabilizing | 1.0 | D | 0.91 | deleterious | None | None | None | None | N |
| R/K | 0.4828 | ambiguous | 0.346 | ambiguous | -1.554 | Destabilizing | 0.998 | D | 0.515 | neutral | None | None | None | None | N |
| R/L | 0.9291 | likely_pathogenic | 0.8923 | pathogenic | -0.865 | Destabilizing | 1.0 | D | 0.758 | deleterious | N | 0.493400287 | None | None | N |
| R/M | 0.9621 | likely_pathogenic | 0.9278 | pathogenic | -1.212 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| R/N | 0.9886 | likely_pathogenic | 0.9812 | pathogenic | -1.171 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| R/P | 0.9987 | likely_pathogenic | 0.998 | pathogenic | -1.153 | Destabilizing | 1.0 | D | 0.883 | deleterious | D | 0.53243318 | None | None | N |
| R/Q | 0.6033 | likely_pathogenic | 0.4078 | ambiguous | -1.255 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.471039616 | None | None | N |
| R/S | 0.9891 | likely_pathogenic | 0.9783 | pathogenic | -2.112 | Highly Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| R/T | 0.984 | likely_pathogenic | 0.9678 | pathogenic | -1.75 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| R/V | 0.9664 | likely_pathogenic | 0.9464 | pathogenic | -1.153 | Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| R/W | 0.9211 | likely_pathogenic | 0.8553 | pathogenic | -0.839 | Destabilizing | 1.0 | D | 0.887 | deleterious | N | 0.499071826 | None | None | N |
| R/Y | 0.9636 | likely_pathogenic | 0.9352 | pathogenic | -0.622 | Destabilizing | 1.0 | D | 0.906 | 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.