Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32253 | 96982;96983;96984 | chr2:178543216;178543215;178543214 | chr2:179407943;179407942;179407941 |
| N2AB | 30612 | 92059;92060;92061 | chr2:178543216;178543215;178543214 | chr2:179407943;179407942;179407941 |
| N2A | 29685 | 89278;89279;89280 | chr2:178543216;178543215;178543214 | chr2:179407943;179407942;179407941 |
| N2B | 23188 | 69787;69788;69789 | chr2:178543216;178543215;178543214 | chr2:179407943;179407942;179407941 |
| Novex-1 | 23313 | 70162;70163;70164 | chr2:178543216;178543215;178543214 | chr2:179407943;179407942;179407941 |
| Novex-2 | 23380 | 70363;70364;70365 | chr2:178543216;178543215;178543214 | chr2:179407943;179407942;179407941 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/D | rs759070210  |
-2.086 | 0.97 | N | 0.672 | 0.336 | 0.584457892069 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65508E-04 |
| V/D | rs759070210 |
-2.086 | 0.97 | N | 0.672 | 0.336 | 0.584457892069 | gnomAD-4.0.0 | 1.59119E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02407E-05 |
| V/I | None | None | 0.656 | N | 0.535 | 0.146 | 0.480123561213 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1033 | likely_benign | 0.1025 | benign | -1.504 | Destabilizing | 0.002 | N | 0.204 | neutral | N | 0.369640787 | None | None | N |
| V/C | 0.6497 | likely_pathogenic | 0.6512 | pathogenic | -1.015 | Destabilizing | 0.994 | D | 0.627 | neutral | None | None | None | None | N |
| V/D | 0.384 | ambiguous | 0.3895 | ambiguous | -1.54 | Destabilizing | 0.97 | D | 0.672 | neutral | N | 0.429419809 | None | None | N |
| V/E | 0.3562 | ambiguous | 0.3614 | ambiguous | -1.498 | Destabilizing | 0.956 | D | 0.596 | neutral | None | None | None | None | N |
| V/F | 0.2383 | likely_benign | 0.2301 | benign | -1.107 | Destabilizing | 0.97 | D | 0.633 | neutral | N | 0.473207872 | None | None | N |
| V/G | 0.1672 | likely_benign | 0.1735 | benign | -1.849 | Destabilizing | 0.698 | D | 0.593 | neutral | N | 0.416394584 | None | None | N |
| V/H | 0.6062 | likely_pathogenic | 0.6095 | pathogenic | -1.295 | Destabilizing | 0.998 | D | 0.71 | prob.delet. | None | None | None | None | N |
| V/I | 0.0965 | likely_benign | 0.0892 | benign | -0.638 | Destabilizing | 0.656 | D | 0.535 | neutral | N | 0.464569746 | None | None | N |
| V/K | 0.4012 | ambiguous | 0.4196 | ambiguous | -1.353 | Destabilizing | 0.956 | D | 0.601 | neutral | None | None | None | None | N |
| V/L | 0.2025 | likely_benign | 0.1933 | benign | -0.638 | Destabilizing | 0.489 | N | 0.475 | neutral | N | 0.447522781 | None | None | N |
| V/M | 0.1496 | likely_benign | 0.1379 | benign | -0.526 | Destabilizing | 0.993 | D | 0.595 | neutral | None | None | None | None | N |
| V/N | 0.2879 | likely_benign | 0.288 | benign | -1.285 | Destabilizing | 0.978 | D | 0.712 | prob.delet. | None | None | None | None | N |
| V/P | 0.896 | likely_pathogenic | 0.9041 | pathogenic | -0.893 | Destabilizing | 0.978 | D | 0.622 | neutral | None | None | None | None | N |
| V/Q | 0.358 | ambiguous | 0.3697 | ambiguous | -1.391 | Destabilizing | 0.978 | D | 0.668 | neutral | None | None | None | None | N |
| V/R | 0.3931 | ambiguous | 0.4206 | ambiguous | -0.833 | Destabilizing | 0.978 | D | 0.691 | prob.neutral | None | None | None | None | N |
| V/S | 0.1541 | likely_benign | 0.1558 | benign | -1.772 | Destabilizing | 0.754 | D | 0.565 | neutral | None | None | None | None | N |
| V/T | 0.1214 | likely_benign | 0.1185 | benign | -1.609 | Destabilizing | 0.86 | D | 0.507 | neutral | None | None | None | None | N |
| V/W | 0.8839 | likely_pathogenic | 0.8784 | pathogenic | -1.345 | Destabilizing | 0.998 | D | 0.719 | prob.delet. | None | None | None | None | N |
| V/Y | 0.6213 | likely_pathogenic | 0.6203 | pathogenic | -1.027 | Destabilizing | 0.993 | D | 0.652 | 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.