Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17261 | 52006;52007;52008 | chr2:178609529;178609528;178609527 | chr2:179474256;179474255;179474254 |
| N2AB | 15620 | 47083;47084;47085 | chr2:178609529;178609528;178609527 | chr2:179474256;179474255;179474254 |
| N2A | 14693 | 44302;44303;44304 | chr2:178609529;178609528;178609527 | chr2:179474256;179474255;179474254 |
| N2B | 8196 | 24811;24812;24813 | chr2:178609529;178609528;178609527 | chr2:179474256;179474255;179474254 |
| Novex-1 | 8321 | 25186;25187;25188 | chr2:178609529;178609528;178609527 | chr2:179474256;179474255;179474254 |
| Novex-2 | 8388 | 25387;25388;25389 | chr2:178609529;178609528;178609527 | chr2:179474256;179474255;179474254 |
| 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 | rs201825412  |
-0.129 | 0.164 | N | 0.226 | 0.049 | None | gnomAD-2.1.1 | 1.15139E-04 | None | None | None | None | N | None | 8.28E-05 | 5.67E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.13594E-04 | 1.41084E-04 |
| R/Q | rs201825412 |
-0.129 | 0.164 | N | 0.226 | 0.049 | None | gnomAD-3.1.2 | 1.51419E-04 | None | None | None | None | N | None | 2.41E-05 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.94481E-04 | 0 | 4.78927E-04 |
| R/Q | rs201825412 |
-0.129 | 0.164 | N | 0.226 | 0.049 | None | gnomAD-4.0.0 | 3.01478E-04 | None | None | None | None | N | None | 5.34745E-05 | 3.33834E-05 | None | 3.38685E-05 | 0 | None | 0 | 0 | 3.9953E-04 | 0 | 1.2823E-04 |
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 | 0.4154 | ambiguous | 0.3875 | ambiguous | -0.327 | Destabilizing | 0.633 | D | 0.456 | neutral | None | None | None | None | N |
| R/C | 0.2379 | likely_benign | 0.2291 | benign | -0.433 | Destabilizing | 0.996 | D | 0.624 | neutral | None | None | None | None | N |
| R/D | 0.8739 | likely_pathogenic | 0.8501 | pathogenic | -0.008 | Destabilizing | 0.775 | D | 0.498 | neutral | None | None | None | None | N |
| R/E | 0.4451 | ambiguous | 0.4196 | ambiguous | 0.055 | Stabilizing | 0.415 | N | 0.425 | neutral | None | None | None | None | N |
| R/F | 0.7705 | likely_pathogenic | 0.7353 | pathogenic | -0.578 | Destabilizing | 0.987 | D | 0.563 | neutral | None | None | None | None | N |
| R/G | 0.4359 | ambiguous | 0.3895 | ambiguous | -0.525 | Destabilizing | 0.868 | D | 0.527 | neutral | N | 0.459540001 | None | None | N |
| R/H | 0.224 | likely_benign | 0.2057 | benign | -0.937 | Destabilizing | 0.961 | D | 0.371 | neutral | None | None | None | None | N |
| R/I | 0.3875 | ambiguous | 0.3721 | ambiguous | 0.162 | Stabilizing | 0.961 | D | 0.563 | neutral | None | None | None | None | N |
| R/K | 0.1132 | likely_benign | 0.114 | benign | -0.326 | Destabilizing | 0.011 | N | 0.241 | neutral | None | None | None | None | N |
| R/L | 0.3865 | ambiguous | 0.3613 | ambiguous | 0.162 | Stabilizing | 0.868 | D | 0.527 | neutral | N | 0.489856901 | None | None | N |
| R/M | 0.3878 | ambiguous | 0.3788 | ambiguous | -0.128 | Destabilizing | 0.961 | D | 0.451 | neutral | None | None | None | None | N |
| R/N | 0.7402 | likely_pathogenic | 0.7132 | pathogenic | 0.002 | Stabilizing | 0.775 | D | 0.43 | neutral | None | None | None | None | N |
| R/P | 0.7781 | likely_pathogenic | 0.7403 | pathogenic | 0.019 | Stabilizing | 0.979 | D | 0.536 | neutral | N | 0.466116036 | None | None | N |
| R/Q | 0.1324 | likely_benign | 0.1266 | benign | -0.174 | Destabilizing | 0.164 | N | 0.226 | neutral | N | 0.480200054 | None | None | N |
| R/S | 0.6554 | likely_pathogenic | 0.6225 | pathogenic | -0.531 | Destabilizing | 0.633 | D | 0.462 | neutral | None | None | None | None | N |
| R/T | 0.4328 | ambiguous | 0.4118 | ambiguous | -0.327 | Destabilizing | 0.775 | D | 0.487 | neutral | None | None | None | None | N |
| R/V | 0.4529 | ambiguous | 0.4402 | ambiguous | 0.019 | Stabilizing | 0.923 | D | 0.529 | neutral | None | None | None | None | N |
| R/W | 0.413 | ambiguous | 0.3768 | ambiguous | -0.524 | Destabilizing | 0.996 | D | 0.669 | neutral | None | None | None | None | N |
| R/Y | 0.6081 | likely_pathogenic | 0.5706 | pathogenic | -0.131 | Destabilizing | 0.961 | D | 0.537 | 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.