Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6089 | 18490;18491;18492 | chr2:178730135;178730134;178730133 | chr2:179594862;179594861;179594860 |
| N2AB | 5772 | 17539;17540;17541 | chr2:178730135;178730134;178730133 | chr2:179594862;179594861;179594860 |
| N2A | 4845 | 14758;14759;14760 | chr2:178730135;178730134;178730133 | chr2:179594862;179594861;179594860 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs754848806  |
-0.015 | 0.767 | N | 0.359 | 0.147 | 0.183819452728 | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.57E-05 | 0 |
| D/E | rs754848806 |
-0.015 | 0.767 | N | 0.359 | 0.147 | 0.183819452728 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | I | None | 0 | 0 | 2.1978E-03 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| D/E | rs754848806 |
-0.015 | 0.767 | N | 0.359 | 0.147 | 0.183819452728 | gnomAD-4.0.0 | 3.90532E-05 | None | None | None | None | I | None | 0 | 1.66928E-05 | None | 0 | 1.11632E-04 | None | 0 | 0 | 4.49307E-05 | 0 | 3.20379E-05 |
| D/G | None | None | 0.998 | N | 0.553 | 0.485 | 0.326881540566 | gnomAD-4.0.0 | 2.40065E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62501E-06 | 0 | 0 |
| D/N | rs560203827 |
0.554 | 0.999 | N | 0.621 | 0.273 | 0.335661160332 | gnomAD-2.1.1 | 7.26E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 5.24109E-04 | None | 0 | 1.78E-05 | 0 |
| D/N | rs560203827 |
0.554 | 0.999 | N | 0.621 | 0.273 | 0.335661160332 | gnomAD-3.1.2 | 4.01E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 1.33333E-03 | 0 |
| D/N | rs560203827 |
0.554 | 0.999 | N | 0.621 | 0.273 | 0.335661160332 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| D/N | rs560203827 |
0.554 | 0.999 | N | 0.621 | 0.273 | 0.335661160332 | gnomAD-4.0.0 | 3.22188E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.58466E-06 | 5.08602E-04 | 3.30622E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1991 | likely_benign | 0.1447 | benign | 0.03 | Stabilizing | 0.999 | D | 0.529 | neutral | N | 0.476395398 | None | None | I |
| D/C | 0.8292 | likely_pathogenic | 0.7224 | pathogenic | 0.013 | Stabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | I |
| D/E | 0.1425 | likely_benign | 0.1391 | benign | -0.316 | Destabilizing | 0.767 | D | 0.359 | neutral | N | 0.476469969 | None | None | I |
| D/F | 0.7498 | likely_pathogenic | 0.6482 | pathogenic | -0.144 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | I |
| D/G | 0.2771 | likely_benign | 0.1992 | benign | -0.071 | Destabilizing | 0.998 | D | 0.553 | neutral | N | 0.481129214 | None | None | I |
| D/H | 0.4292 | ambiguous | 0.3187 | benign | 0.369 | Stabilizing | 1.0 | D | 0.646 | neutral | N | 0.520167605 | None | None | I |
| D/I | 0.4566 | ambiguous | 0.3404 | ambiguous | 0.223 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| D/K | 0.5194 | ambiguous | 0.3777 | ambiguous | 0.483 | Stabilizing | 0.999 | D | 0.574 | neutral | None | None | None | None | I |
| D/L | 0.5334 | ambiguous | 0.422 | ambiguous | 0.223 | Stabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | I |
| D/M | 0.7063 | likely_pathogenic | 0.6098 | pathogenic | 0.119 | Stabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/N | 0.1475 | likely_benign | 0.1175 | benign | 0.331 | Stabilizing | 0.999 | D | 0.621 | neutral | N | 0.508873176 | None | None | I |
| D/P | 0.7341 | likely_pathogenic | 0.6321 | pathogenic | 0.177 | Stabilizing | 1.0 | D | 0.622 | neutral | None | None | None | None | I |
| D/Q | 0.4551 | ambiguous | 0.3671 | ambiguous | 0.313 | Stabilizing | 0.999 | D | 0.654 | neutral | None | None | None | None | I |
| D/R | 0.5746 | likely_pathogenic | 0.4297 | ambiguous | 0.635 | Stabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | I |
| D/S | 0.1667 | likely_benign | 0.1343 | benign | 0.232 | Stabilizing | 0.997 | D | 0.566 | neutral | None | None | None | None | I |
| D/T | 0.2861 | likely_benign | 0.2182 | benign | 0.311 | Stabilizing | 1.0 | D | 0.606 | neutral | None | None | None | None | I |
| D/V | 0.2807 | likely_benign | 0.2018 | benign | 0.177 | Stabilizing | 0.999 | D | 0.661 | neutral | N | 0.46494904 | None | None | I |
| D/W | 0.9503 | likely_pathogenic | 0.9179 | pathogenic | -0.128 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| D/Y | 0.4154 | ambiguous | 0.3106 | benign | 0.075 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | N | 0.488023414 | None | None | I |
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.