Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25874 | 77845;77846;77847 | chr2:178568512;178568511;178568510 | chr2:179433239;179433238;179433237 |
| N2AB | 24233 | 72922;72923;72924 | chr2:178568512;178568511;178568510 | chr2:179433239;179433238;179433237 |
| N2A | 23306 | 70141;70142;70143 | chr2:178568512;178568511;178568510 | chr2:179433239;179433238;179433237 |
| N2B | 16809 | 50650;50651;50652 | chr2:178568512;178568511;178568510 | chr2:179433239;179433238;179433237 |
| Novex-1 | 16934 | 51025;51026;51027 | chr2:178568512;178568511;178568510 | chr2:179433239;179433238;179433237 |
| Novex-2 | 17001 | 51226;51227;51228 | chr2:178568512;178568511;178568510 | chr2:179433239;179433238;179433237 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | None | None | 0.999 | D | 0.639 | 0.68 | 0.368369118721 | gnomAD-4.0.0 | 6.84341E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52258E-05 | None | 0 | 0 | 0 | 0 | 0 |
| N/H | None | None | 1.0 | D | 0.745 | 0.734 | 0.418467456957 | gnomAD-4.0.0 | 6.84341E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99611E-07 | 0 | 0 |
| N/K | rs766227814  |
-0.556 | 1.0 | D | 0.737 | 0.516 | 0.318252033908 | gnomAD-2.1.1 | 9.56E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.94502E-04 | 0 |
| N/K | rs766227814 |
-0.556 | 1.0 | D | 0.737 | 0.516 | 0.318252033908 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| N/K | rs766227814 |
-0.556 | 1.0 | D | 0.737 | 0.516 | 0.318252033908 | gnomAD-4.0.0 | 3.71907E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08661E-06 | 0 | 0 |
| N/S | rs1706835764 |
None | 0.999 | N | 0.599 | 0.615 | 0.31411915649 | gnomAD-4.0.0 | 1.59199E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85968E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.9601 | likely_pathogenic | 0.9422 | pathogenic | -0.748 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| N/C | 0.8232 | likely_pathogenic | 0.7886 | pathogenic | -0.164 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| N/D | 0.9599 | likely_pathogenic | 0.9556 | pathogenic | -1.395 | Destabilizing | 0.999 | D | 0.639 | neutral | D | 0.526090078 | None | None | N |
| N/E | 0.9962 | likely_pathogenic | 0.9955 | pathogenic | -1.3 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| N/F | 0.9979 | likely_pathogenic | 0.9976 | pathogenic | -0.605 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| N/G | 0.9189 | likely_pathogenic | 0.9033 | pathogenic | -1.068 | Destabilizing | 0.999 | D | 0.581 | neutral | None | None | None | None | N |
| N/H | 0.9222 | likely_pathogenic | 0.9165 | pathogenic | -0.917 | Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.553855571 | None | None | N |
| N/I | 0.9859 | likely_pathogenic | 0.9805 | pathogenic | 0.06 | Stabilizing | 1.0 | D | 0.708 | prob.delet. | D | 0.531231866 | None | None | N |
| N/K | 0.9974 | likely_pathogenic | 0.9967 | pathogenic | -0.374 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | D | 0.541827703 | None | None | N |
| N/L | 0.9542 | likely_pathogenic | 0.948 | pathogenic | 0.06 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| N/M | 0.9768 | likely_pathogenic | 0.974 | pathogenic | 0.543 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| N/P | 0.994 | likely_pathogenic | 0.9936 | pathogenic | -0.18 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| N/Q | 0.9948 | likely_pathogenic | 0.9934 | pathogenic | -1.144 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| N/R | 0.9946 | likely_pathogenic | 0.9931 | pathogenic | -0.338 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| N/S | 0.3771 | ambiguous | 0.3224 | benign | -0.979 | Destabilizing | 0.999 | D | 0.599 | neutral | N | 0.481955076 | None | None | N |
| N/T | 0.7828 | likely_pathogenic | 0.7587 | pathogenic | -0.719 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | D | 0.529964418 | None | None | N |
| N/V | 0.9678 | likely_pathogenic | 0.9566 | pathogenic | -0.18 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| N/W | 0.9992 | likely_pathogenic | 0.999 | pathogenic | -0.443 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| N/Y | 0.9841 | likely_pathogenic | 0.9828 | pathogenic | -0.166 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | D | 0.553855571 | 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.