Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28336 | 85231;85232;85233 | chr2:178561126;178561125;178561124 | chr2:179425853;179425852;179425851 |
| N2AB | 26695 | 80308;80309;80310 | chr2:178561126;178561125;178561124 | chr2:179425853;179425852;179425851 |
| N2A | 25768 | 77527;77528;77529 | chr2:178561126;178561125;178561124 | chr2:179425853;179425852;179425851 |
| N2B | 19271 | 58036;58037;58038 | chr2:178561126;178561125;178561124 | chr2:179425853;179425852;179425851 |
| Novex-1 | 19396 | 58411;58412;58413 | chr2:178561126;178561125;178561124 | chr2:179425853;179425852;179425851 |
| Novex-2 | 19463 | 58612;58613;58614 | chr2:178561126;178561125;178561124 | chr2:179425853;179425852;179425851 |
| 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/G | None | None | 0.055 | N | 0.45 | 0.225 | 0.514587094315 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-06 | 0 | 0 |
| V/L | rs375593513  |
-0.741 | None | N | 0.14 | 0.088 | None | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 1.65673E-04 |
| V/L | rs375593513 |
-0.741 | None | N | 0.14 | 0.088 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/L | rs375593513 |
-0.741 | None | N | 0.14 | 0.088 | None | gnomAD-4.0.0 | 3.09842E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.98361E-05 | 0 | 4.80338E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2825 | likely_benign | 0.2352 | benign | -1.055 | Destabilizing | 0.012 | N | 0.278 | neutral | N | 0.519345593 | None | None | N |
| V/C | 0.6254 | likely_pathogenic | 0.6309 | pathogenic | -0.932 | Destabilizing | 0.628 | D | 0.483 | neutral | None | None | None | None | N |
| V/D | 0.5577 | ambiguous | 0.4737 | ambiguous | -0.445 | Destabilizing | 0.171 | N | 0.545 | neutral | N | 0.491510501 | None | None | N |
| V/E | 0.4606 | ambiguous | 0.3936 | ambiguous | -0.523 | Destabilizing | 0.072 | N | 0.506 | neutral | None | None | None | None | N |
| V/F | 0.1256 | likely_benign | 0.1202 | benign | -1.116 | Destabilizing | None | N | 0.201 | neutral | N | 0.448485573 | None | None | N |
| V/G | 0.3727 | ambiguous | 0.3009 | benign | -1.257 | Destabilizing | 0.055 | N | 0.45 | neutral | N | 0.467783932 | None | None | N |
| V/H | 0.5734 | likely_pathogenic | 0.5359 | ambiguous | -0.693 | Destabilizing | 0.628 | D | 0.506 | neutral | None | None | None | None | N |
| V/I | 0.0608 | likely_benign | 0.0617 | benign | -0.645 | Destabilizing | None | N | 0.143 | neutral | N | 0.438980655 | None | None | N |
| V/K | 0.4665 | ambiguous | 0.4166 | ambiguous | -0.677 | Destabilizing | 0.072 | N | 0.497 | neutral | None | None | None | None | N |
| V/L | 0.1165 | likely_benign | 0.1137 | benign | -0.645 | Destabilizing | None | N | 0.14 | neutral | N | 0.449234934 | None | None | N |
| V/M | 0.1214 | likely_benign | 0.1166 | benign | -0.504 | Destabilizing | 0.214 | N | 0.448 | neutral | None | None | None | None | N |
| V/N | 0.3592 | ambiguous | 0.313 | benign | -0.417 | Destabilizing | 0.214 | N | 0.541 | neutral | None | None | None | None | N |
| V/P | 0.6167 | likely_pathogenic | 0.5586 | ambiguous | -0.746 | Destabilizing | 0.356 | N | 0.545 | neutral | None | None | None | None | N |
| V/Q | 0.4232 | ambiguous | 0.3746 | ambiguous | -0.679 | Destabilizing | 0.356 | N | 0.509 | neutral | None | None | None | None | N |
| V/R | 0.4051 | ambiguous | 0.355 | ambiguous | -0.127 | Destabilizing | 0.214 | N | 0.536 | neutral | None | None | None | None | N |
| V/S | 0.3046 | likely_benign | 0.2565 | benign | -0.949 | Destabilizing | 0.038 | N | 0.437 | neutral | None | None | None | None | N |
| V/T | 0.2567 | likely_benign | 0.2225 | benign | -0.916 | Destabilizing | None | N | 0.169 | neutral | None | None | None | None | N |
| V/W | 0.7037 | likely_pathogenic | 0.6729 | pathogenic | -1.134 | Destabilizing | 0.864 | D | 0.509 | neutral | None | None | None | None | N |
| V/Y | 0.407 | ambiguous | 0.3968 | ambiguous | -0.847 | Destabilizing | 0.038 | N | 0.401 | 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.