Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7545 | 22858;22859;22860 | chr2:178722030;178722029;178722028 | chr2:179586757;179586756;179586755 |
| N2AB | 7228 | 21907;21908;21909 | chr2:178722030;178722029;178722028 | chr2:179586757;179586756;179586755 |
| N2A | 6301 | 19126;19127;19128 | chr2:178722030;178722029;178722028 | chr2:179586757;179586756;179586755 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs72648969  |
0.213 | 0.91 | N | 0.453 | 0.212 | None | gnomAD-2.1.1 | 2.11743E-03 | None | None | None | None | I | None | 6.61978E-04 | 6.22524E-04 | None | 1.47998E-02 | 0 | None | 8.83508E-04 | None | 4.80577E-04 | 2.70996E-03 | 2.24909E-03 |
| R/Q | rs72648969 |
0.213 | 0.91 | N | 0.453 | 0.212 | None | gnomAD-3.1.2 | 1.90634E-03 | None | None | None | None | I | None | 5.30939E-04 | 7.86164E-04 | 0 | 1.12392E-02 | 0 | None | 1.88395E-04 | 0 | 3E-03 | 1.44867E-03 | 1.91022E-03 |
| R/Q | rs72648969 |
0.213 | 0.91 | N | 0.453 | 0.212 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| R/Q | rs72648969 |
0.213 | 0.91 | N | 0.453 | 0.212 | None | gnomAD-4.0.0 | 3.03338E-03 | None | None | None | None | I | None | 5.19972E-04 | 6.50065E-04 | None | 1.39941E-02 | 2.22906E-05 | None | 6.40585E-04 | 0 | 3.39123E-03 | 1.31877E-03 | 3.84246E-03 |
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 | 0.3197 | likely_benign | 0.31 | benign | -0.091 | Destabilizing | 0.013 | N | 0.209 | neutral | None | None | None | None | I |
| R/C | 0.2442 | likely_benign | 0.2645 | benign | -0.266 | Destabilizing | 0.995 | D | 0.42 | neutral | None | None | None | None | I |
| R/D | 0.5425 | ambiguous | 0.5274 | ambiguous | -0.116 | Destabilizing | 0.704 | D | 0.537 | neutral | None | None | None | None | I |
| R/E | 0.3013 | likely_benign | 0.2818 | benign | -0.066 | Destabilizing | 0.329 | N | 0.395 | neutral | None | None | None | None | I |
| R/F | 0.4819 | ambiguous | 0.4907 | ambiguous | -0.361 | Destabilizing | 0.944 | D | 0.446 | neutral | None | None | None | None | I |
| R/G | 0.2419 | likely_benign | 0.2401 | benign | -0.263 | Destabilizing | 0.653 | D | 0.43 | neutral | D | 0.536233135 | None | None | I |
| R/H | 0.0811 | likely_benign | 0.0839 | benign | -0.667 | Destabilizing | 0.017 | N | 0.21 | neutral | None | None | None | None | I |
| R/I | 0.2 | likely_benign | 0.1896 | benign | 0.321 | Stabilizing | 0.893 | D | 0.529 | neutral | None | None | None | None | I |
| R/K | 0.0781 | likely_benign | 0.0778 | benign | -0.161 | Destabilizing | 0.003 | N | 0.119 | neutral | None | None | None | None | I |
| R/L | 0.1922 | likely_benign | 0.1893 | benign | 0.321 | Stabilizing | 0.485 | N | 0.436 | neutral | N | 0.473837882 | None | None | I |
| R/M | 0.2205 | likely_benign | 0.2112 | benign | -0.034 | Destabilizing | 0.981 | D | 0.471 | neutral | None | None | None | None | I |
| R/N | 0.3625 | ambiguous | 0.363 | ambiguous | 0.056 | Stabilizing | 0.704 | D | 0.398 | neutral | None | None | None | None | I |
| R/P | 0.7451 | likely_pathogenic | 0.7492 | pathogenic | 0.203 | Stabilizing | 0.902 | D | 0.569 | neutral | N | 0.512306188 | None | None | I |
| R/Q | 0.0931 | likely_benign | 0.0926 | benign | -0.068 | Destabilizing | 0.91 | D | 0.453 | neutral | N | 0.454403973 | None | None | I |
| R/S | 0.3553 | ambiguous | 0.3555 | ambiguous | -0.311 | Destabilizing | 0.329 | N | 0.414 | neutral | None | None | None | None | I |
| R/T | 0.1694 | likely_benign | 0.1582 | benign | -0.136 | Destabilizing | 0.013 | N | 0.209 | neutral | None | None | None | None | I |
| R/V | 0.2591 | likely_benign | 0.2487 | benign | 0.203 | Stabilizing | 0.543 | D | 0.483 | neutral | None | None | None | None | I |
| R/W | 0.1973 | likely_benign | 0.1945 | benign | -0.416 | Destabilizing | 0.995 | D | 0.431 | neutral | None | None | None | None | I |
| R/Y | 0.3301 | likely_benign | 0.3394 | benign | -0.011 | Destabilizing | 0.893 | D | 0.513 | 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.