Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28590 | 85993;85994;85995 | chr2:178560364;178560363;178560362 | chr2:179425091;179425090;179425089 |
| N2AB | 26949 | 81070;81071;81072 | chr2:178560364;178560363;178560362 | chr2:179425091;179425090;179425089 |
| N2A | 26022 | 78289;78290;78291 | chr2:178560364;178560363;178560362 | chr2:179425091;179425090;179425089 |
| N2B | 19525 | 58798;58799;58800 | chr2:178560364;178560363;178560362 | chr2:179425091;179425090;179425089 |
| Novex-1 | 19650 | 59173;59174;59175 | chr2:178560364;178560363;178560362 | chr2:179425091;179425090;179425089 |
| Novex-2 | 19717 | 59374;59375;59376 | chr2:178560364;178560363;178560362 | chr2:179425091;179425090;179425089 |
| 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/L | None | None | 1.0 | N | 0.737 | 0.577 | 0.706951834606 | gnomAD-4.0.0 | 2.05277E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69845E-06 | 0 | 0 |
| R/P | rs375667028  |
-1.536 | 1.0 | D | 0.871 | 0.691 | 0.692726414735 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| R/P | rs375667028 |
-1.536 | 1.0 | D | 0.871 | 0.691 | 0.692726414735 | gnomAD-4.0.0 | 6.84258E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52258E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs375667028 |
-1.037 | 1.0 | N | 0.666 | 0.485 | None | gnomAD-2.1.1 | 1.25107E-04 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 3.27E-05 | None | 4.80461E-04 | 1.64255E-04 | 0 |
| R/Q | rs375667028 |
-1.037 | 1.0 | N | 0.666 | 0.485 | None | gnomAD-3.1.2 | 1.1834E-04 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 5.65504E-04 | 0 | 1.47054E-04 | 0 | 0 |
| R/Q | rs375667028 |
-1.037 | 1.0 | N | 0.666 | 0.485 | None | gnomAD-4.0.0 | 9.04842E-05 | None | None | None | None | N | None | 4.0047E-05 | 1.66733E-05 | None | 0 | 0 | None | 4.37623E-04 | 0 | 8.73066E-05 | 8.78522E-05 | 4.80415E-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 | 0.9654 | likely_pathogenic | 0.9572 | pathogenic | -1.795 | Destabilizing | 0.999 | D | 0.507 | neutral | None | None | None | None | N |
| R/C | 0.5029 | ambiguous | 0.4526 | ambiguous | -1.788 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| R/D | 0.995 | likely_pathogenic | 0.9943 | pathogenic | -0.704 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| R/E | 0.9319 | likely_pathogenic | 0.9275 | pathogenic | -0.522 | Destabilizing | 0.999 | D | 0.506 | neutral | None | None | None | None | N |
| R/F | 0.9582 | likely_pathogenic | 0.9471 | pathogenic | -1.255 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| R/G | 0.9289 | likely_pathogenic | 0.9133 | pathogenic | -2.137 | Highly Destabilizing | 1.0 | D | 0.737 | prob.delet. | D | 0.524444236 | None | None | N |
| R/H | 0.2866 | likely_benign | 0.2639 | benign | -2.052 | Highly Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/I | 0.9327 | likely_pathogenic | 0.9132 | pathogenic | -0.824 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| R/K | 0.2223 | likely_benign | 0.2107 | benign | -1.505 | Destabilizing | 0.998 | D | 0.466 | neutral | None | None | None | None | N |
| R/L | 0.8126 | likely_pathogenic | 0.7891 | pathogenic | -0.824 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.510352453 | None | None | N |
| R/M | 0.8519 | likely_pathogenic | 0.8309 | pathogenic | -1.202 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| R/N | 0.9771 | likely_pathogenic | 0.9738 | pathogenic | -1.172 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | N |
| R/P | 0.9983 | likely_pathogenic | 0.9977 | pathogenic | -1.133 | Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.547574921 | None | None | N |
| R/Q | 0.2997 | likely_benign | 0.2744 | benign | -1.207 | Destabilizing | 1.0 | D | 0.666 | neutral | N | 0.487827198 | None | None | N |
| R/S | 0.9832 | likely_pathogenic | 0.979 | pathogenic | -2.129 | Highly Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| R/T | 0.9584 | likely_pathogenic | 0.9491 | pathogenic | -1.742 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| R/V | 0.9481 | likely_pathogenic | 0.9353 | pathogenic | -1.133 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| R/W | 0.6174 | likely_pathogenic | 0.5741 | pathogenic | -0.737 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| R/Y | 0.8684 | likely_pathogenic | 0.843 | pathogenic | -0.548 | Destabilizing | 1.0 | D | 0.896 | 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.