Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1295 | 4108;4109;4110 | chr2:178779309;178779308;178779307 | chr2:179644036;179644035;179644034 |
| N2AB | 1295 | 4108;4109;4110 | chr2:178779309;178779308;178779307 | chr2:179644036;179644035;179644034 |
| N2A | 1295 | 4108;4109;4110 | chr2:178779309;178779308;178779307 | chr2:179644036;179644035;179644034 |
| N2B | 1249 | 3970;3971;3972 | chr2:178779309;178779308;178779307 | chr2:179644036;179644035;179644034 |
| Novex-1 | 1249 | 3970;3971;3972 | chr2:178779309;178779308;178779307 | chr2:179644036;179644035;179644034 |
| Novex-2 | 1249 | 3970;3971;3972 | chr2:178779309;178779308;178779307 | chr2:179644036;179644035;179644034 |
| Novex-3 | 1295 | 4108;4109;4110 | chr2:178779309;178779308;178779307 | chr2:179644036;179644035;179644034 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs1552280  |
0.202 | None | N | 0.157 | 0.182 | None | gnomAD-2.1.1 | 9.60146E-01 | None | None | None | None | I | None | 8.67871E-01 | 9.39765E-01 | None | 9.92169E-01 | 8.80483E-01 | None | 9.57565E-01 | None | 9.78089E-01 | 9.89934E-01 | 9.70711E-01 |
| S/L | rs1552280 |
0.202 | None | N | 0.157 | 0.182 | None | gnomAD-3.1.2 | 9.47703E-01 | None | None | None | None | I | None | 8.68937E-01 | 9.63878E-01 | 8.43202E-01 | 9.93948E-01 | 8.72353E-01 | None | 9.80222E-01 | 9.77848E-01 | 9.91315E-01 | 9.51346E-01 | 9.47897E-01 |
| S/L | rs1552280 |
0.202 | None | N | 0.157 | 0.182 | None | 1000 genomes | 9.20128E-01 | None | None | None | None | I | None | 8.495E-01 | 9.496E-01 | None | None | 8.829E-01 | 9.92E-01 | None | None | None | 9.591E-01 | None |
| S/L | rs1552280 |
0.202 | None | N | 0.157 | 0.182 | None | gnomAD-4.0.0 | 9.77851E-01 | None | None | None | None | I | None | 8.67148E-01 | 9.48334E-01 | None | 9.92903E-01 | 8.7004E-01 | None | 9.77766E-01 | 9.84488E-01 | 9.92126E-01 | 9.58061E-01 | 9.69941E-01 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0664 | likely_benign | 0.0674 | benign | -0.6 | Destabilizing | None | N | 0.147 | neutral | N | 0.444068896 | None | None | I |
| S/C | 0.1218 | likely_benign | 0.1157 | benign | -0.351 | Destabilizing | 0.051 | N | 0.457 | neutral | None | None | None | None | I |
| S/D | 0.376 | ambiguous | 0.3671 | ambiguous | -0.385 | Destabilizing | 0.003 | N | 0.229 | neutral | None | None | None | None | I |
| S/E | 0.2692 | likely_benign | 0.2624 | benign | -0.405 | Destabilizing | 0.003 | N | 0.207 | neutral | None | None | None | None | I |
| S/F | 0.0938 | likely_benign | 0.087 | benign | -0.791 | Destabilizing | 0.001 | N | 0.325 | neutral | None | None | None | None | I |
| S/G | 0.1401 | likely_benign | 0.1325 | benign | -0.839 | Destabilizing | 0.001 | N | 0.198 | neutral | None | None | None | None | I |
| S/H | 0.1571 | likely_benign | 0.1514 | benign | -1.317 | Destabilizing | 0.116 | N | 0.467 | neutral | None | None | None | None | I |
| S/I | 0.0472 | likely_benign | 0.0487 | benign | -0.074 | Destabilizing | None | N | 0.161 | neutral | None | None | None | None | I |
| S/K | 0.3678 | ambiguous | 0.3465 | ambiguous | -0.789 | Destabilizing | 0.001 | N | 0.201 | neutral | None | None | None | None | I |
| S/L | 0.0329 | likely_benign | 0.0357 | benign | -0.074 | Destabilizing | None | N | 0.157 | neutral | N | 0.467324023 | None | None | I |
| S/M | 0.0604 | likely_benign | 0.0639 | benign | 0.254 | Stabilizing | None | N | 0.165 | neutral | None | None | None | None | I |
| S/N | 0.1233 | likely_benign | 0.1231 | benign | -0.684 | Destabilizing | 0.003 | N | 0.224 | neutral | None | None | None | None | I |
| S/P | 0.6824 | likely_pathogenic | 0.6125 | pathogenic | -0.215 | Destabilizing | 0.008 | N | 0.341 | neutral | N | 0.51334847 | None | None | I |
| S/Q | 0.1711 | likely_benign | 0.1655 | benign | -0.853 | Destabilizing | 0.003 | N | 0.261 | neutral | None | None | None | None | I |
| S/R | 0.3307 | likely_benign | 0.2943 | benign | -0.606 | Destabilizing | 0.003 | N | 0.335 | neutral | None | None | None | None | I |
| S/T | 0.0597 | likely_benign | 0.0613 | benign | -0.676 | Destabilizing | None | N | 0.128 | neutral | N | 0.422790519 | None | None | I |
| S/V | 0.055 | likely_benign | 0.0559 | benign | -0.215 | Destabilizing | None | N | 0.168 | neutral | None | None | None | None | I |
| S/W | 0.1815 | likely_benign | 0.1596 | benign | -0.797 | Destabilizing | 0.116 | N | 0.54 | neutral | None | None | None | None | I |
| S/Y | 0.1384 | likely_benign | 0.133 | benign | -0.544 | Destabilizing | 0.003 | N | 0.363 | neutral | None | None | None | None | I |
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.