Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25750 | 77473;77474;77475 | chr2:178568884;178568883;178568882 | chr2:179433611;179433610;179433609 |
| N2AB | 24109 | 72550;72551;72552 | chr2:178568884;178568883;178568882 | chr2:179433611;179433610;179433609 |
| N2A | 23182 | 69769;69770;69771 | chr2:178568884;178568883;178568882 | chr2:179433611;179433610;179433609 |
| N2B | 16685 | 50278;50279;50280 | chr2:178568884;178568883;178568882 | chr2:179433611;179433610;179433609 |
| Novex-1 | 16810 | 50653;50654;50655 | chr2:178568884;178568883;178568882 | chr2:179433611;179433610;179433609 |
| Novex-2 | 16877 | 50854;50855;50856 | chr2:178568884;178568883;178568882 | chr2:179433611;179433610;179433609 |
| 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/P | rs368038362  |
-0.157 | 0.832 | N | 0.497 | 0.315 | 0.317958651998 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.03E-05 | 7.81E-06 | 0 |
| R/P | rs368038362 |
-0.157 | 0.832 | N | 0.497 | 0.315 | 0.317958651998 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/P | rs368038362 |
-0.157 | 0.832 | N | 0.497 | 0.315 | 0.317958651998 | gnomAD-4.0.0 | 1.8599E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.56927E-05 | 0 | 1.69556E-06 | 0 | 0 |
| R/Q | rs368038362 |
0.01 | 0.175 | N | 0.207 | 0.057 | None | gnomAD-2.1.1 | 1.14375E-04 | None | None | None | None | N | None | 8.27E-05 | 2.83E-05 | None | 9.68E-05 | 0 | None | 0 | None | 0 | 1.95334E-04 | 4.22297E-04 |
| R/Q | rs368038362 |
0.01 | 0.175 | N | 0.207 | 0.057 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 7.24E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.02984E-04 | 0 | 0 |
| R/Q | rs368038362 |
0.01 | 0.175 | N | 0.207 | 0.057 | None | gnomAD-4.0.0 | 1.10974E-04 | None | None | None | None | N | None | 5.34245E-05 | 3.33589E-05 | None | 3.38066E-05 | 0 | None | 0 | 1.64636E-04 | 1.38188E-04 | 3.2946E-05 | 8.00846E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2267 | likely_benign | 0.2317 | benign | -0.416 | Destabilizing | 0.007 | N | 0.238 | neutral | None | None | None | None | N |
| R/C | 0.1326 | likely_benign | 0.14 | benign | -0.401 | Destabilizing | 0.965 | D | 0.383 | neutral | None | None | None | None | N |
| R/D | 0.5412 | ambiguous | 0.5337 | ambiguous | 0.043 | Stabilizing | 0.561 | D | 0.437 | neutral | None | None | None | None | N |
| R/E | 0.2652 | likely_benign | 0.2676 | benign | 0.159 | Stabilizing | 0.209 | N | 0.267 | neutral | None | None | None | None | N |
| R/F | 0.397 | ambiguous | 0.392 | ambiguous | -0.299 | Destabilizing | 0.818 | D | 0.441 | neutral | None | None | None | None | N |
| R/G | 0.2167 | likely_benign | 0.2217 | benign | -0.712 | Destabilizing | 0.503 | D | 0.378 | neutral | N | 0.450352442 | None | None | N |
| R/H | 0.0777 | likely_benign | 0.0787 | benign | -1.111 | Destabilizing | 0.901 | D | 0.415 | neutral | None | None | None | None | N |
| R/I | 0.1774 | likely_benign | 0.1769 | benign | 0.363 | Stabilizing | 0.004 | N | 0.331 | neutral | None | None | None | None | N |
| R/K | 0.0795 | likely_benign | 0.0789 | benign | -0.457 | Destabilizing | 0.209 | N | 0.277 | neutral | None | None | None | None | N |
| R/L | 0.1792 | likely_benign | 0.1808 | benign | 0.363 | Stabilizing | 0.148 | N | 0.331 | neutral | N | 0.451176374 | None | None | N |
| R/M | 0.2083 | likely_benign | 0.2015 | benign | -0.069 | Destabilizing | 0.818 | D | 0.41 | neutral | None | None | None | None | N |
| R/N | 0.3522 | ambiguous | 0.3398 | benign | -0.022 | Destabilizing | 0.561 | D | 0.279 | neutral | None | None | None | None | N |
| R/P | 0.6024 | likely_pathogenic | 0.5898 | pathogenic | 0.125 | Stabilizing | 0.832 | D | 0.497 | neutral | N | 0.4414636 | None | None | N |
| R/Q | 0.0842 | likely_benign | 0.0856 | benign | -0.138 | Destabilizing | 0.175 | N | 0.207 | neutral | N | 0.421627045 | None | None | N |
| R/S | 0.2712 | likely_benign | 0.278 | benign | -0.637 | Destabilizing | 0.021 | N | 0.252 | neutral | None | None | None | None | N |
| R/T | 0.118 | likely_benign | 0.1192 | benign | -0.347 | Destabilizing | 0.007 | N | 0.225 | neutral | None | None | None | None | N |
| R/V | 0.1952 | likely_benign | 0.1984 | benign | 0.125 | Stabilizing | 0.083 | N | 0.361 | neutral | None | None | None | None | N |
| R/W | 0.1722 | likely_benign | 0.1723 | benign | -0.081 | Destabilizing | 0.991 | D | 0.397 | neutral | None | None | None | None | N |
| R/Y | 0.299 | likely_benign | 0.2936 | benign | 0.244 | Stabilizing | 0.901 | D | 0.439 | 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.