Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8301 | 25126;25127;25128 | chr2:178718105;178718104;178718103 | chr2:179582832;179582831;179582830 |
| N2AB | 7984 | 24175;24176;24177 | chr2:178718105;178718104;178718103 | chr2:179582832;179582831;179582830 |
| N2A | 7057 | 21394;21395;21396 | chr2:178718105;178718104;178718103 | chr2:179582832;179582831;179582830 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/L | rs763397399  |
0.711 | 0.01 | N | 0.287 | 0.393 | 0.554235320232 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| H/L | rs763397399 |
0.711 | 0.01 | N | 0.287 | 0.393 | 0.554235320232 | gnomAD-4.0.0 | 1.59372E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02499E-05 |
| H/N | rs375389220 |
0.09 | 0.002 | N | 0.209 | 0.23 | 0.190952846119 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92604E-04 | None | 0 | 0 | 0 | 0 | 0 |
| H/N | rs375389220 |
0.09 | 0.002 | N | 0.209 | 0.23 | 0.190952846119 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| H/N | rs375389220 |
0.09 | 0.002 | N | 0.209 | 0.23 | 0.190952846119 | gnomAD-4.0.0 | 6.56901E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.9305E-04 | None | 0 | 0 | 0 | 0 | 0 |
| H/Y | rs375389220 |
0.925 | 0.178 | N | 0.4 | 0.275 | 0.332133492242 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| H/Y | rs375389220 |
0.925 | 0.178 | N | 0.4 | 0.275 | 0.332133492242 | gnomAD-4.0.0 | 2.05425E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69856E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.2005 | likely_benign | 0.2636 | benign | 0.472 | Stabilizing | None | N | 0.11 | neutral | None | None | None | None | N |
| H/C | 0.2703 | likely_benign | 0.3185 | benign | 0.657 | Stabilizing | 0.353 | N | 0.332 | neutral | None | None | None | None | N |
| H/D | 0.0736 | likely_benign | 0.0893 | benign | -0.123 | Destabilizing | None | N | 0.096 | neutral | N | 0.330346972 | None | None | N |
| H/E | 0.1802 | likely_benign | 0.2253 | benign | -0.112 | Destabilizing | 0.003 | N | 0.169 | neutral | None | None | None | None | N |
| H/F | 0.3463 | ambiguous | 0.3904 | ambiguous | 1.042 | Stabilizing | 0.223 | N | 0.417 | neutral | None | None | None | None | N |
| H/G | 0.1417 | likely_benign | 0.1712 | benign | 0.236 | Stabilizing | None | N | 0.103 | neutral | None | None | None | None | N |
| H/I | 0.3796 | ambiguous | 0.4763 | ambiguous | 1.059 | Stabilizing | 0.063 | N | 0.448 | neutral | None | None | None | None | N |
| H/K | 0.1791 | likely_benign | 0.2211 | benign | 0.388 | Stabilizing | 0.014 | N | 0.291 | neutral | None | None | None | None | N |
| H/L | 0.153 | likely_benign | 0.1792 | benign | 1.059 | Stabilizing | 0.01 | N | 0.287 | neutral | N | 0.460354084 | None | None | N |
| H/M | 0.4178 | ambiguous | 0.4835 | ambiguous | 0.717 | Stabilizing | 0.419 | N | 0.338 | neutral | None | None | None | None | N |
| H/N | 0.0441 | likely_benign | 0.0495 | benign | 0.272 | Stabilizing | 0.002 | N | 0.209 | neutral | N | 0.364979621 | None | None | N |
| H/P | 0.2266 | likely_benign | 0.3064 | benign | 0.888 | Stabilizing | 0.016 | N | 0.357 | neutral | N | 0.47841977 | None | None | N |
| H/Q | 0.1228 | likely_benign | 0.1492 | benign | 0.346 | Stabilizing | 0.026 | N | 0.312 | neutral | N | 0.438920019 | None | None | N |
| H/R | 0.105 | likely_benign | 0.123 | benign | -0.125 | Destabilizing | 0.01 | N | 0.301 | neutral | N | 0.43453292 | None | None | N |
| H/S | 0.1401 | likely_benign | 0.1742 | benign | 0.403 | Stabilizing | None | N | 0.109 | neutral | None | None | None | None | N |
| H/T | 0.1933 | likely_benign | 0.2454 | benign | 0.509 | Stabilizing | 0.005 | N | 0.253 | neutral | None | None | None | None | N |
| H/V | 0.2972 | likely_benign | 0.3808 | ambiguous | 0.888 | Stabilizing | 0.014 | N | 0.315 | neutral | None | None | None | None | N |
| H/W | 0.503 | ambiguous | 0.5767 | pathogenic | 0.956 | Stabilizing | 0.911 | D | 0.332 | neutral | None | None | None | None | N |
| H/Y | 0.1121 | likely_benign | 0.1314 | benign | 1.227 | Stabilizing | 0.178 | N | 0.4 | neutral | N | 0.478939845 | 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.