Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9955 | 30088;30089;30090 | chr2:178704609;178704608;178704607 | chr2:179569336;179569335;179569334 |
| N2AB | 9638 | 29137;29138;29139 | chr2:178704609;178704608;178704607 | chr2:179569336;179569335;179569334 |
| N2A | 8711 | 26356;26357;26358 | chr2:178704609;178704608;178704607 | chr2:179569336;179569335;179569334 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 | rs182332374  |
-0.502 | 0.175 | None | 0.301 | 0.1 | None | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.69E-05 | 0 |
| R/Q | rs182332374 |
-0.502 | 0.175 | None | 0.301 | 0.1 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92382E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs182332374 |
-0.502 | 0.175 | None | 0.301 | 0.1 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/Q | rs182332374 |
-0.502 | 0.175 | None | 0.301 | 0.1 | None | gnomAD-4.0.0 | 1.11615E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.22836E-05 | None | 0 | 0 | 1.35692E-05 | 0 | 1.60174E-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 | 0.8515 | likely_pathogenic | 0.7275 | pathogenic | -0.914 | Destabilizing | 0.447 | N | 0.552 | neutral | None | None | None | None | N |
| R/C | 0.3794 | ambiguous | 0.2953 | benign | -0.901 | Destabilizing | 0.992 | D | 0.589 | neutral | None | None | None | None | N |
| R/D | 0.9655 | likely_pathogenic | 0.9306 | pathogenic | -0.503 | Destabilizing | 0.85 | D | 0.577 | neutral | None | None | None | None | N |
| R/E | 0.7123 | likely_pathogenic | 0.5681 | pathogenic | -0.404 | Destabilizing | 0.447 | N | 0.568 | neutral | None | None | None | None | N |
| R/F | 0.8975 | likely_pathogenic | 0.8356 | pathogenic | -0.915 | Destabilizing | 0.85 | D | 0.597 | neutral | None | None | None | None | N |
| R/G | 0.8237 | likely_pathogenic | 0.6594 | pathogenic | -1.202 | Destabilizing | 0.756 | D | 0.569 | neutral | None | None | None | None | N |
| R/H | 0.1569 | likely_benign | 0.1299 | benign | -1.37 | Destabilizing | 0.012 | N | 0.307 | neutral | None | None | None | None | N |
| R/I | 0.559 | ambiguous | 0.4186 | ambiguous | -0.142 | Destabilizing | 0.739 | D | 0.577 | neutral | None | None | None | None | N |
| R/K | 0.164 | likely_benign | 0.1348 | benign | -1.133 | Destabilizing | 0.25 | N | 0.548 | neutral | None | None | None | None | N |
| R/L | 0.6512 | likely_pathogenic | 0.5107 | ambiguous | -0.142 | Destabilizing | 0.01 | N | 0.349 | neutral | None | None | None | None | N |
| R/M | 0.7033 | likely_pathogenic | 0.5627 | ambiguous | -0.268 | Destabilizing | 0.85 | D | 0.587 | neutral | None | None | None | None | N |
| R/N | 0.8748 | likely_pathogenic | 0.7921 | pathogenic | -0.544 | Destabilizing | 0.617 | D | 0.559 | neutral | None | None | None | None | N |
| R/P | 0.998 | likely_pathogenic | 0.9933 | pathogenic | -0.379 | Destabilizing | 0.957 | D | 0.591 | neutral | None | None | None | None | N |
| R/Q | 0.182 | likely_benign | 0.1275 | benign | -0.797 | Destabilizing | 0.175 | N | 0.301 | neutral | None | None | None | None | N |
| R/S | 0.849 | likely_pathogenic | 0.7309 | pathogenic | -1.262 | Destabilizing | 0.447 | N | 0.562 | neutral | None | None | None | None | N |
| R/T | 0.5417 | ambiguous | 0.3823 | ambiguous | -1.0 | Destabilizing | 0.617 | D | 0.577 | neutral | None | None | None | None | N |
| R/V | 0.6651 | likely_pathogenic | 0.5457 | ambiguous | -0.379 | Destabilizing | 0.447 | N | 0.587 | neutral | None | None | None | None | N |
| R/W | 0.6071 | likely_pathogenic | 0.4626 | ambiguous | -0.578 | Destabilizing | 0.992 | D | 0.596 | neutral | None | None | None | None | N |
| R/Y | 0.7973 | likely_pathogenic | 0.7078 | pathogenic | -0.255 | Destabilizing | 0.85 | D | 0.59 | neutral | 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.