Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25880 | 77863;77864;77865 | chr2:178568494;178568493;178568492 | chr2:179433221;179433220;179433219 |
| N2AB | 24239 | 72940;72941;72942 | chr2:178568494;178568493;178568492 | chr2:179433221;179433220;179433219 |
| N2A | 23312 | 70159;70160;70161 | chr2:178568494;178568493;178568492 | chr2:179433221;179433220;179433219 |
| N2B | 16815 | 50668;50669;50670 | chr2:178568494;178568493;178568492 | chr2:179433221;179433220;179433219 |
| Novex-1 | 16940 | 51043;51044;51045 | chr2:178568494;178568493;178568492 | chr2:179433221;179433220;179433219 |
| Novex-2 | 17007 | 51244;51245;51246 | chr2:178568494;178568493;178568492 | chr2:179433221;179433220;179433219 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs56018860  |
-0.456 | None | D | 0.122 | 0.121 | None | gnomAD-2.1.1 | 2.57414E-02 | None | None | None | None | N | None | 4.83751E-03 | 3.35071E-02 | None | 1.46233E-02 | 6.13285E-02 | None | 6.04812E-03 | None | 4.79447E-02 | 2.3361E-02 | 2.65823E-02 |
| T/A | rs56018860 |
-0.456 | None | D | 0.122 | 0.121 | None | gnomAD-3.1.2 | 2.02291E-02 | None | None | None | None | N | None | 4.48842E-03 | 2.16621E-02 | 3.07018E-02 | 1.90202E-02 | 6.15802E-02 | None | 4.46664E-02 | 6.32911E-03 | 2.34005E-02 | 8.285E-03 | 1.95985E-02 |
| T/A | rs56018860 |
-0.456 | None | D | 0.122 | 0.121 | None | 1000 genomes | 2.23642E-02 | None | None | None | None | N | None | 8E-04 | 2.45E-02 | None | None | 6.05E-02 | 2.68E-02 | None | None | None | 6.1E-03 | None |
| T/A | rs56018860 |
-0.456 | None | D | 0.122 | 0.121 | None | gnomAD-4.0.0 | 2.28803E-02 | None | None | None | None | N | None | 4.27897E-03 | 2.93382E-02 | None | 1.48709E-02 | 6.32258E-02 | None | 4.76935E-02 | 9.74562E-03 | 2.24293E-02 | 6.74207E-03 | 2.16779E-02 |
| T/I | rs1332594097 |
0.092 | 0.096 | N | 0.435 | 0.295 | 0.421674004627 | 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 |
| T/I | rs1332594097 |
0.092 | 0.096 | N | 0.435 | 0.295 | 0.421674004627 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78469E-04 |
| T/I | rs1332594097 |
0.092 | 0.096 | N | 0.435 | 0.295 | 0.421674004627 | gnomAD-4.0.0 | 1.36367E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44118E-05 | 1.09796E-05 | 6.40677E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0751 | likely_benign | 0.0736 | benign | -0.559 | Destabilizing | None | N | 0.122 | neutral | D | 0.535523846 | None | None | N |
| T/C | 0.2784 | likely_benign | 0.2608 | benign | -0.421 | Destabilizing | 0.667 | D | 0.482 | neutral | None | None | None | None | N |
| T/D | 0.2352 | likely_benign | 0.2235 | benign | 0.111 | Stabilizing | None | N | 0.201 | neutral | None | None | None | None | N |
| T/E | 0.1877 | likely_benign | 0.1756 | benign | 0.069 | Stabilizing | 0.002 | N | 0.221 | neutral | None | None | None | None | N |
| T/F | 0.1605 | likely_benign | 0.1445 | benign | -0.814 | Destabilizing | 0.667 | D | 0.561 | neutral | None | None | None | None | N |
| T/G | 0.2056 | likely_benign | 0.1812 | benign | -0.754 | Destabilizing | 0.055 | N | 0.371 | neutral | None | None | None | None | N |
| T/H | 0.1596 | likely_benign | 0.1548 | benign | -1.017 | Destabilizing | 0.667 | D | 0.487 | neutral | None | None | None | None | N |
| T/I | 0.1061 | likely_benign | 0.0911 | benign | -0.15 | Destabilizing | 0.096 | N | 0.435 | neutral | N | 0.504525189 | None | None | N |
| T/K | 0.1413 | likely_benign | 0.1379 | benign | -0.563 | Destabilizing | 0.042 | N | 0.397 | neutral | D | 0.525960213 | None | None | N |
| T/L | 0.0876 | likely_benign | 0.0786 | benign | -0.15 | Destabilizing | 0.055 | N | 0.382 | neutral | None | None | None | None | N |
| T/M | 0.0744 | likely_benign | 0.0707 | benign | 0.004 | Stabilizing | 0.667 | D | 0.485 | neutral | None | None | None | None | N |
| T/N | 0.092 | likely_benign | 0.0853 | benign | -0.401 | Destabilizing | 0.055 | N | 0.355 | neutral | None | None | None | None | N |
| T/P | 0.2104 | likely_benign | 0.2056 | benign | -0.255 | Destabilizing | 0.301 | N | 0.447 | neutral | D | 0.525098206 | None | None | N |
| T/Q | 0.154 | likely_benign | 0.1487 | benign | -0.6 | Destabilizing | 0.22 | N | 0.443 | neutral | None | None | None | None | N |
| T/R | 0.1331 | likely_benign | 0.1309 | benign | -0.294 | Destabilizing | 0.175 | N | 0.489 | neutral | N | 0.518458238 | None | None | N |
| T/S | 0.0833 | likely_benign | 0.0782 | benign | -0.663 | Destabilizing | None | N | 0.115 | neutral | N | 0.440669458 | None | None | N |
| T/V | 0.088 | likely_benign | 0.0786 | benign | -0.255 | Destabilizing | None | N | 0.142 | neutral | None | None | None | None | N |
| T/W | 0.4633 | ambiguous | 0.4334 | ambiguous | -0.765 | Destabilizing | 0.958 | D | 0.509 | neutral | None | None | None | None | N |
| T/Y | 0.1857 | likely_benign | 0.1724 | benign | -0.518 | Destabilizing | 0.667 | D | 0.528 | 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.