Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6855 | 20788;20789;20790 | chr2:178725641;178725640;178725639 | chr2:179590368;179590367;179590366 |
| N2AB | 6538 | 19837;19838;19839 | chr2:178725641;178725640;178725639 | chr2:179590368;179590367;179590366 |
| N2A | 5611 | 17056;17057;17058 | chr2:178725641;178725640;178725639 | chr2:179590368;179590367;179590366 |
| 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/G | None | None | 0.012 | N | 0.225 | 0.317 | 0.475430695062 | gnomAD-4.0.0 | 6.99796E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.13641E-07 | 0 | 0 |
| R/I | rs1231976753  |
0.562 | 0.029 | N | 0.337 | 0.268 | 0.561751252162 | gnomAD-2.1.1 | 8.97E-06 | None | None | None | None | N | None | 0 | 0 | None | 2.56871E-04 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/I | rs1231976753 |
0.562 | 0.029 | N | 0.337 | 0.268 | 0.561751252162 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 2.88184E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/I | rs1231976753 |
0.562 | 0.029 | N | 0.337 | 0.268 | 0.561751252162 | gnomAD-4.0.0 | 3.16376E-06 | None | None | None | None | N | None | 0 | 0 | None | 1.44352E-04 | 0 | None | 0 | 0 | 8.60415E-07 | 0 | 0 |
| R/S | rs2079210485 |
None | 0.001 | N | 0.193 | 0.115 | 0.321108458156 | gnomAD-4.0.0 | 1.39989E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.08673E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2611 | likely_benign | 0.2357 | benign | -0.268 | Destabilizing | None | N | 0.16 | neutral | None | None | None | None | N |
| R/C | 0.1792 | likely_benign | 0.1504 | benign | -0.465 | Destabilizing | 0.628 | D | 0.31 | neutral | None | None | None | None | N |
| R/D | 0.6305 | likely_pathogenic | 0.5946 | pathogenic | -0.046 | Destabilizing | 0.072 | N | 0.314 | neutral | None | None | None | None | N |
| R/E | 0.3237 | likely_benign | 0.3028 | benign | 0.079 | Stabilizing | 0.016 | N | 0.188 | neutral | None | None | None | None | N |
| R/F | 0.3883 | ambiguous | 0.3456 | ambiguous | -0.178 | Destabilizing | 0.214 | N | 0.409 | neutral | None | None | None | None | N |
| R/G | 0.2355 | likely_benign | 0.2036 | benign | -0.551 | Destabilizing | 0.012 | N | 0.225 | neutral | N | 0.516434018 | None | None | N |
| R/H | 0.101 | likely_benign | 0.095 | benign | -0.962 | Destabilizing | 0.356 | N | 0.277 | neutral | None | None | None | None | N |
| R/I | 0.1628 | likely_benign | 0.1546 | benign | 0.474 | Stabilizing | 0.029 | N | 0.337 | neutral | N | 0.516940997 | None | None | N |
| R/K | 0.0752 | likely_benign | 0.0708 | benign | -0.348 | Destabilizing | None | N | 0.087 | neutral | N | 0.50927582 | None | None | N |
| R/L | 0.1825 | likely_benign | 0.1735 | benign | 0.474 | Stabilizing | None | N | 0.214 | neutral | None | None | None | None | N |
| R/M | 0.1876 | likely_benign | 0.1779 | benign | -0.119 | Destabilizing | 0.214 | N | 0.307 | neutral | None | None | None | None | N |
| R/N | 0.4201 | ambiguous | 0.3705 | ambiguous | -0.171 | Destabilizing | 0.072 | N | 0.173 | neutral | None | None | None | None | N |
| R/P | 0.8478 | likely_pathogenic | 0.8616 | pathogenic | 0.249 | Stabilizing | 0.136 | N | 0.345 | neutral | None | None | None | None | N |
| R/Q | 0.0987 | likely_benign | 0.0941 | benign | -0.191 | Destabilizing | 0.038 | N | 0.196 | neutral | None | None | None | None | N |
| R/S | 0.3139 | likely_benign | 0.2692 | benign | -0.663 | Destabilizing | 0.001 | N | 0.193 | neutral | N | 0.47287509 | None | None | N |
| R/T | 0.1582 | likely_benign | 0.1369 | benign | -0.363 | Destabilizing | 0.012 | N | 0.235 | neutral | N | 0.491442208 | None | None | N |
| R/V | 0.1989 | likely_benign | 0.1873 | benign | 0.249 | Stabilizing | 0.016 | N | 0.246 | neutral | None | None | None | None | N |
| R/W | 0.1824 | likely_benign | 0.1718 | benign | -0.059 | Destabilizing | 0.864 | D | 0.317 | neutral | None | None | None | None | N |
| R/Y | 0.3211 | likely_benign | 0.2894 | benign | 0.289 | Stabilizing | 0.628 | D | 0.389 | 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.