Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17879 | 53860;53861;53862 | chr2:178605660;178605659;178605658 | chr2:179470387;179470386;179470385 |
| N2AB | 16238 | 48937;48938;48939 | chr2:178605660;178605659;178605658 | chr2:179470387;179470386;179470385 |
| N2A | 15311 | 46156;46157;46158 | chr2:178605660;178605659;178605658 | chr2:179470387;179470386;179470385 |
| N2B | 8814 | 26665;26666;26667 | chr2:178605660;178605659;178605658 | chr2:179470387;179470386;179470385 |
| Novex-1 | 8939 | 27040;27041;27042 | chr2:178605660;178605659;178605658 | chr2:179470387;179470386;179470385 |
| Novex-2 | 9006 | 27241;27242;27243 | chr2:178605660;178605659;178605658 | chr2:179470387;179470386;179470385 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.991 | N | 0.695 | 0.246 | 0.406668915854 | gnomAD-4.0.0 | 1.60561E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8882E-06 | 0 | 0 |
| I/T | rs760585965  |
-2.403 | 0.939 | N | 0.784 | 0.439 | None | gnomAD-2.1.1 | 1.63E-05 | None | None | None | None | N | None | 6.49E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.69E-05 | 0 |
| I/T | rs760585965 |
-2.403 | 0.939 | N | 0.784 | 0.439 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs760585965 |
-2.403 | 0.939 | N | 0.784 | 0.439 | None | gnomAD-4.0.0 | 4.41593E-05 | None | None | None | None | N | None | 2.67816E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.78236E-05 | 0 | 1.60818E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9201 | likely_pathogenic | 0.9046 | pathogenic | -2.576 | Highly Destabilizing | 0.91 | D | 0.72 | prob.delet. | None | None | None | None | N |
| I/C | 0.9591 | likely_pathogenic | 0.9474 | pathogenic | -1.719 | Destabilizing | 0.999 | D | 0.781 | deleterious | None | None | None | None | N |
| I/D | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -2.985 | Highly Destabilizing | 0.998 | D | 0.829 | deleterious | None | None | None | None | N |
| I/E | 0.9989 | likely_pathogenic | 0.9989 | pathogenic | -2.638 | Highly Destabilizing | 0.993 | D | 0.83 | deleterious | None | None | None | None | N |
| I/F | 0.9279 | likely_pathogenic | 0.9194 | pathogenic | -1.539 | Destabilizing | 0.982 | D | 0.742 | deleterious | N | 0.471573049 | None | None | N |
| I/G | 0.997 | likely_pathogenic | 0.9965 | pathogenic | -3.216 | Highly Destabilizing | 0.993 | D | 0.826 | deleterious | None | None | None | None | N |
| I/H | 0.9993 | likely_pathogenic | 0.9992 | pathogenic | -3.015 | Highly Destabilizing | 0.999 | D | 0.807 | deleterious | None | None | None | None | N |
| I/K | 0.9987 | likely_pathogenic | 0.9989 | pathogenic | -1.794 | Destabilizing | 0.993 | D | 0.829 | deleterious | None | None | None | None | N |
| I/L | 0.4609 | ambiguous | 0.416 | ambiguous | -0.646 | Destabilizing | 0.58 | D | 0.39 | neutral | N | 0.476666678 | None | None | N |
| I/M | 0.5089 | ambiguous | 0.4874 | ambiguous | -0.869 | Destabilizing | 0.991 | D | 0.695 | prob.neutral | N | 0.502205414 | None | None | N |
| I/N | 0.9958 | likely_pathogenic | 0.9957 | pathogenic | -2.541 | Highly Destabilizing | 0.997 | D | 0.837 | deleterious | N | 0.500859479 | None | None | N |
| I/P | 0.999 | likely_pathogenic | 0.9988 | pathogenic | -1.281 | Destabilizing | 0.998 | D | 0.824 | deleterious | None | None | None | None | N |
| I/Q | 0.9981 | likely_pathogenic | 0.9983 | pathogenic | -2.103 | Highly Destabilizing | 0.998 | D | 0.843 | deleterious | None | None | None | None | N |
| I/R | 0.9974 | likely_pathogenic | 0.9976 | pathogenic | -2.063 | Highly Destabilizing | 0.993 | D | 0.842 | deleterious | None | None | None | None | N |
| I/S | 0.9867 | likely_pathogenic | 0.9852 | pathogenic | -3.123 | Highly Destabilizing | 0.991 | D | 0.801 | deleterious | N | 0.488996195 | None | None | N |
| I/T | 0.9634 | likely_pathogenic | 0.9616 | pathogenic | -2.592 | Highly Destabilizing | 0.939 | D | 0.784 | deleterious | N | 0.493351061 | None | None | N |
| I/V | 0.099 | likely_benign | 0.0892 | benign | -1.281 | Destabilizing | 0.02 | N | 0.221 | neutral | N | 0.402846497 | None | None | N |
| I/W | 0.9991 | likely_pathogenic | 0.9991 | pathogenic | -1.863 | Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | N |
| I/Y | 0.9956 | likely_pathogenic | 0.9952 | pathogenic | -1.66 | Destabilizing | 0.993 | D | 0.811 | deleterious | 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.