Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25121 | 75586;75587;75588 | chr2:178570771;178570770;178570769 | chr2:179435498;179435497;179435496 |
| N2AB | 23480 | 70663;70664;70665 | chr2:178570771;178570770;178570769 | chr2:179435498;179435497;179435496 |
| N2A | 22553 | 67882;67883;67884 | chr2:178570771;178570770;178570769 | chr2:179435498;179435497;179435496 |
| N2B | 16056 | 48391;48392;48393 | chr2:178570771;178570770;178570769 | chr2:179435498;179435497;179435496 |
| Novex-1 | 16181 | 48766;48767;48768 | chr2:178570771;178570770;178570769 | chr2:179435498;179435497;179435496 |
| Novex-2 | 16248 | 48967;48968;48969 | chr2:178570771;178570770;178570769 | chr2:179435498;179435497;179435496 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs751021006  |
-1.578 | 0.062 | N | 0.49 | 0.298 | 0.672509336206 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs751021006 |
-1.578 | 0.062 | N | 0.49 | 0.298 | 0.672509336206 | gnomAD-4.0.0 | 1.59168E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77439E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs199508062 |
-0.804 | None | N | 0.096 | 0.06 | None | gnomAD-2.1.1 | 1.14367E-04 | None | None | None | None | N | None | 1.24039E-03 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.40528E-04 |
| I/V | rs199508062 |
-0.804 | None | N | 0.096 | 0.06 | None | gnomAD-3.1.2 | 3.28774E-04 | None | None | None | None | N | None | 1.20715E-03 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs199508062 |
-0.804 | None | N | 0.096 | 0.06 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/V | rs199508062 |
-0.804 | None | N | 0.096 | 0.06 | None | gnomAD-4.0.0 | 6.01155E-05 | None | None | None | None | N | None | 1.24013E-03 | 3.33333E-05 | None | 0 | 0 | None | 0 | 0 | 8.47738E-07 | 0 | 1.60092E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3483 | ambiguous | 0.3503 | ambiguous | -2.016 | Highly Destabilizing | 0.035 | N | 0.459 | neutral | None | None | None | None | N |
| I/C | 0.7381 | likely_pathogenic | 0.7463 | pathogenic | -1.427 | Destabilizing | 0.824 | D | 0.484 | neutral | None | None | None | None | N |
| I/D | 0.8772 | likely_pathogenic | 0.8975 | pathogenic | -1.657 | Destabilizing | 0.555 | D | 0.586 | neutral | None | None | None | None | N |
| I/E | 0.7464 | likely_pathogenic | 0.7809 | pathogenic | -1.521 | Destabilizing | 0.555 | D | 0.601 | neutral | None | None | None | None | N |
| I/F | 0.195 | likely_benign | 0.1923 | benign | -1.175 | Destabilizing | 0.188 | N | 0.449 | neutral | N | 0.510370858 | None | None | N |
| I/G | 0.8201 | likely_pathogenic | 0.8288 | pathogenic | -2.479 | Highly Destabilizing | 0.555 | D | 0.595 | neutral | None | None | None | None | N |
| I/H | 0.6717 | likely_pathogenic | 0.6944 | pathogenic | -1.742 | Destabilizing | 0.935 | D | 0.571 | neutral | None | None | None | None | N |
| I/K | 0.5659 | likely_pathogenic | 0.5952 | pathogenic | -1.554 | Destabilizing | 0.555 | D | 0.599 | neutral | None | None | None | None | N |
| I/L | 0.106 | likely_benign | 0.1056 | benign | -0.746 | Destabilizing | None | N | 0.093 | neutral | N | 0.461215302 | None | None | N |
| I/M | 0.1024 | likely_benign | 0.0998 | benign | -0.698 | Destabilizing | 0.541 | D | 0.472 | neutral | D | 0.529827238 | None | None | N |
| I/N | 0.5785 | likely_pathogenic | 0.6317 | pathogenic | -1.652 | Destabilizing | 0.741 | D | 0.595 | neutral | D | 0.529070997 | None | None | N |
| I/P | 0.9092 | likely_pathogenic | 0.9139 | pathogenic | -1.142 | Destabilizing | 0.791 | D | 0.587 | neutral | None | None | None | None | N |
| I/Q | 0.6318 | likely_pathogenic | 0.6544 | pathogenic | -1.626 | Destabilizing | 0.791 | D | 0.587 | neutral | None | None | None | None | N |
| I/R | 0.47 | ambiguous | 0.5048 | ambiguous | -1.151 | Destabilizing | 0.555 | D | 0.594 | neutral | None | None | None | None | N |
| I/S | 0.4972 | ambiguous | 0.5285 | ambiguous | -2.365 | Highly Destabilizing | 0.117 | N | 0.573 | neutral | N | 0.510117368 | None | None | N |
| I/T | 0.229 | likely_benign | 0.2428 | benign | -2.084 | Highly Destabilizing | 0.062 | N | 0.49 | neutral | N | 0.484264433 | None | None | N |
| I/V | 0.0624 | likely_benign | 0.0617 | benign | -1.142 | Destabilizing | None | N | 0.096 | neutral | N | 0.43735422 | None | None | N |
| I/W | 0.8231 | likely_pathogenic | 0.8081 | pathogenic | -1.396 | Destabilizing | 0.935 | D | 0.635 | neutral | None | None | None | None | N |
| I/Y | 0.5888 | likely_pathogenic | 0.6031 | pathogenic | -1.121 | Destabilizing | 0.555 | D | 0.527 | 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.