Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31144 | 93655;93656;93657 | chr2:178548196;178548195;178548194 | chr2:179412923;179412922;179412921 |
| N2AB | 29503 | 88732;88733;88734 | chr2:178548196;178548195;178548194 | chr2:179412923;179412922;179412921 |
| N2A | 28576 | 85951;85952;85953 | chr2:178548196;178548195;178548194 | chr2:179412923;179412922;179412921 |
| N2B | 22079 | 66460;66461;66462 | chr2:178548196;178548195;178548194 | chr2:179412923;179412922;179412921 |
| Novex-1 | 22204 | 66835;66836;66837 | chr2:178548196;178548195;178548194 | chr2:179412923;179412922;179412921 |
| Novex-2 | 22271 | 67036;67037;67038 | chr2:178548196;178548195;178548194 | chr2:179412923;179412922;179412921 |
| 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/G | rs770088691  |
-0.371 | 1.0 | N | 0.585 | 0.422 | 0.508934680445 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/G | rs770088691 |
-0.371 | 1.0 | N | 0.585 | 0.422 | 0.508934680445 | gnomAD-4.0.0 | 4.78923E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.95604E-05 | 1.65645E-05 |
| R/Q | rs561941986 |
0.281 | 1.0 | N | 0.675 | 0.304 | 0.24896430686 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 9.95E-05 | 0 | None | 0 | None | 4.64E-05 | 1.78E-05 | 0 |
| R/Q | rs561941986 |
0.281 | 1.0 | N | 0.675 | 0.304 | 0.24896430686 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs561941986 |
0.281 | 1.0 | N | 0.675 | 0.304 | 0.24896430686 | gnomAD-4.0.0 | 9.91538E-06 | None | None | None | None | N | None | 2.67151E-05 | 0 | None | 3.37838E-05 | 0 | None | 1.56226E-05 | 0 | 9.32358E-06 | 0 | 1.60102E-05 |
| R/W | rs770088691 |
-0.363 | 1.0 | N | 0.722 | 0.486 | 0.505335117028 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| R/W | rs770088691 |
-0.363 | 1.0 | N | 0.722 | 0.486 | 0.505335117028 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78469E-04 |
| R/W | rs770088691 |
-0.363 | 1.0 | N | 0.722 | 0.486 | 0.505335117028 | gnomAD-4.0.0 | 5.57738E-06 | None | None | None | None | N | None | 2.67094E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23801E-06 | 1.09803E-05 | 1.60102E-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 | 0.7182 | likely_pathogenic | 0.6296 | pathogenic | -0.021 | Destabilizing | 0.999 | D | 0.579 | neutral | None | None | None | None | N |
| R/C | 0.3227 | likely_benign | 0.2956 | benign | -0.096 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| R/D | 0.9203 | likely_pathogenic | 0.8861 | pathogenic | -0.082 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| R/E | 0.7592 | likely_pathogenic | 0.6946 | pathogenic | -0.026 | Destabilizing | 0.999 | D | 0.598 | neutral | None | None | None | None | N |
| R/F | 0.7986 | likely_pathogenic | 0.7462 | pathogenic | -0.267 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| R/G | 0.6436 | likely_pathogenic | 0.5482 | ambiguous | -0.206 | Destabilizing | 1.0 | D | 0.585 | neutral | N | 0.475440101 | None | None | N |
| R/H | 0.1727 | likely_benign | 0.1564 | benign | -0.728 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| R/I | 0.5693 | likely_pathogenic | 0.4868 | ambiguous | 0.428 | Stabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | N |
| R/K | 0.1619 | likely_benign | 0.1834 | benign | -0.053 | Destabilizing | 0.998 | D | 0.453 | neutral | None | None | None | None | N |
| R/L | 0.524 | ambiguous | 0.4379 | ambiguous | 0.428 | Stabilizing | 1.0 | D | 0.585 | neutral | N | 0.519153592 | None | None | N |
| R/M | 0.632 | likely_pathogenic | 0.5643 | pathogenic | 0.056 | Stabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | N |
| R/N | 0.8555 | likely_pathogenic | 0.8072 | pathogenic | 0.217 | Stabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| R/P | 0.6709 | likely_pathogenic | 0.5553 | ambiguous | 0.298 | Stabilizing | 1.0 | D | 0.648 | neutral | N | 0.411097834 | None | None | N |
| R/Q | 0.2154 | likely_benign | 0.19 | benign | 0.098 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | N | 0.493775145 | None | None | N |
| R/S | 0.8315 | likely_pathogenic | 0.771 | pathogenic | -0.13 | Destabilizing | 1.0 | D | 0.62 | neutral | None | None | None | None | N |
| R/T | 0.6707 | likely_pathogenic | 0.5819 | pathogenic | 0.055 | Stabilizing | 1.0 | D | 0.612 | neutral | None | None | None | None | N |
| R/V | 0.6156 | likely_pathogenic | 0.5637 | ambiguous | 0.298 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| R/W | 0.3594 | ambiguous | 0.2821 | benign | -0.331 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | N | 0.492359875 | None | None | N |
| R/Y | 0.6209 | likely_pathogenic | 0.5625 | ambiguous | 0.079 | Stabilizing | 1.0 | D | 0.659 | 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.