Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18105 | 54538;54539;54540 | chr2:178604776;178604775;178604774 | chr2:179469503;179469502;179469501 |
| N2AB | 16464 | 49615;49616;49617 | chr2:178604776;178604775;178604774 | chr2:179469503;179469502;179469501 |
| N2A | 15537 | 46834;46835;46836 | chr2:178604776;178604775;178604774 | chr2:179469503;179469502;179469501 |
| N2B | 9040 | 27343;27344;27345 | chr2:178604776;178604775;178604774 | chr2:179469503;179469502;179469501 |
| Novex-1 | 9165 | 27718;27719;27720 | chr2:178604776;178604775;178604774 | chr2:179469503;179469502;179469501 |
| Novex-2 | 9232 | 27919;27920;27921 | chr2:178604776;178604775;178604774 | chr2:179469503;179469502;179469501 |
| 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/C | rs765739434  |
-1.81 | 1.0 | N | 0.802 | 0.415 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| R/C | rs765739434 |
-1.81 | 1.0 | N | 0.802 | 0.415 | None | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs765739434 |
-1.81 | 1.0 | N | 0.802 | 0.415 | None | gnomAD-4.0.0 | 2.0472E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.3751E-05 | 4.39986E-05 | 1.60298E-05 |
| R/G | None | None | 0.996 | N | 0.741 | 0.418 | 0.580927594641 | gnomAD-4.0.0 | 6.84844E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00105E-07 | 0 | 0 |
| R/H | rs760383112 |
-2.794 | 1.0 | N | 0.679 | 0.41 | 0.279370189704 | gnomAD-2.1.1 | 3.94E-05 | None | None | None | None | N | None | 0 | 1.70232E-04 | None | 0 | 0 | None | 9.83E-05 | None | 0 | 1.56E-05 | 0 |
| R/H | rs760383112 |
-2.794 | 1.0 | N | 0.679 | 0.41 | 0.279370189704 | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 2.42E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs760383112 |
-2.794 | 1.0 | N | 0.679 | 0.41 | 0.279370189704 | gnomAD-4.0.0 | 1.67479E-05 | None | None | None | None | N | None | 1.33693E-05 | 1.50306E-04 | None | 0 | 0 | None | 1.56367E-05 | 0 | 8.48211E-06 | 3.29939E-05 | 4.80893E-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 | 0.9073 | likely_pathogenic | 0.9198 | pathogenic | -1.735 | Destabilizing | 0.985 | D | 0.684 | prob.neutral | None | None | None | None | N |
| R/C | 0.3452 | ambiguous | 0.3286 | benign | -1.689 | Destabilizing | 1.0 | D | 0.802 | deleterious | N | 0.485659881 | None | None | N |
| R/D | 0.991 | likely_pathogenic | 0.9946 | pathogenic | -0.741 | Destabilizing | 0.998 | D | 0.753 | deleterious | None | None | None | None | N |
| R/E | 0.887 | likely_pathogenic | 0.9146 | pathogenic | -0.539 | Destabilizing | 0.985 | D | 0.591 | neutral | None | None | None | None | N |
| R/F | 0.8977 | likely_pathogenic | 0.9048 | pathogenic | -1.035 | Destabilizing | 0.996 | D | 0.827 | deleterious | None | None | None | None | N |
| R/G | 0.8682 | likely_pathogenic | 0.8918 | pathogenic | -2.107 | Highly Destabilizing | 0.996 | D | 0.741 | deleterious | N | 0.477044005 | None | None | N |
| R/H | 0.3318 | likely_benign | 0.3552 | ambiguous | -2.01 | Highly Destabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.482982261 | None | None | N |
| R/I | 0.711 | likely_pathogenic | 0.7642 | pathogenic | -0.676 | Destabilizing | 0.991 | D | 0.801 | deleterious | None | None | None | None | N |
| R/K | 0.1708 | likely_benign | 0.1682 | benign | -1.435 | Destabilizing | 0.469 | N | 0.241 | neutral | None | None | None | None | N |
| R/L | 0.6576 | likely_pathogenic | 0.6878 | pathogenic | -0.676 | Destabilizing | 0.984 | D | 0.718 | prob.delet. | N | 0.514326563 | None | None | N |
| R/M | 0.668 | likely_pathogenic | 0.6785 | pathogenic | -1.073 | Destabilizing | 0.931 | D | 0.534 | neutral | None | None | None | None | N |
| R/N | 0.9624 | likely_pathogenic | 0.9744 | pathogenic | -1.227 | Destabilizing | 0.998 | D | 0.663 | neutral | None | None | None | None | N |
| R/P | 0.9977 | likely_pathogenic | 0.9982 | pathogenic | -1.014 | Destabilizing | 1.0 | D | 0.797 | deleterious | N | 0.509226817 | None | None | N |
| R/Q | 0.2447 | likely_benign | 0.2604 | benign | -1.173 | Destabilizing | 0.996 | D | 0.644 | neutral | None | None | None | None | N |
| R/S | 0.9595 | likely_pathogenic | 0.9673 | pathogenic | -2.137 | Highly Destabilizing | 0.992 | D | 0.717 | prob.delet. | N | 0.507379161 | None | None | N |
| R/T | 0.8697 | likely_pathogenic | 0.8918 | pathogenic | -1.717 | Destabilizing | 0.993 | D | 0.724 | prob.delet. | None | None | None | None | N |
| R/V | 0.7748 | likely_pathogenic | 0.8173 | pathogenic | -1.014 | Destabilizing | 0.971 | D | 0.757 | deleterious | None | None | None | None | N |
| R/W | 0.5803 | likely_pathogenic | 0.5598 | ambiguous | -0.526 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| R/Y | 0.7715 | likely_pathogenic | 0.7961 | pathogenic | -0.357 | Destabilizing | 0.999 | D | 0.776 | 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.