Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29433 | 88522;88523;88524 | chr2:178556857;178556856;178556855 | chr2:179421584;179421583;179421582 |
| N2AB | 27792 | 83599;83600;83601 | chr2:178556857;178556856;178556855 | chr2:179421584;179421583;179421582 |
| N2A | 26865 | 80818;80819;80820 | chr2:178556857;178556856;178556855 | chr2:179421584;179421583;179421582 |
| N2B | 20368 | 61327;61328;61329 | chr2:178556857;178556856;178556855 | chr2:179421584;179421583;179421582 |
| Novex-1 | 20493 | 61702;61703;61704 | chr2:178556857;178556856;178556855 | chr2:179421584;179421583;179421582 |
| Novex-2 | 20560 | 61903;61904;61905 | chr2:178556857;178556856;178556855 | chr2:179421584;179421583;179421582 |
| 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/H | rs189202799  |
0.482 | 0.994 | N | 0.833 | 0.359 | 0.275215494804 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs189202799 |
0.482 | 0.994 | N | 0.833 | 0.359 | 0.275215494804 | gnomAD-4.0.0 | 6.84408E-07 | None | None | None | None | N | None | 2.98739E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs189202799 |
0.412 | 0.979 | N | 0.785 | 0.348 | None | gnomAD-2.1.1 | 4.50763E-04 | None | None | None | None | N | None | 4.46355E-03 | 3.39732E-04 | None | 0 | 0 | None | 0 | None | 0 | 3.91E-05 | 1.40607E-04 |
| D/N | rs189202799 |
0.412 | 0.979 | N | 0.785 | 0.348 | None | gnomAD-3.1.2 | 1.39347E-03 | None | None | None | None | N | None | 4.58627E-03 | 6.54707E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 3.83142E-03 |
| D/N | rs189202799 |
0.412 | 0.979 | N | 0.785 | 0.348 | None | 1000 genomes | 1.19808E-03 | None | None | None | None | N | None | 4.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| D/N | rs189202799 |
0.412 | 0.979 | N | 0.785 | 0.348 | None | gnomAD-4.0.0 | 2.70861E-04 | None | None | None | None | N | None | 4.6785E-03 | 4.33276E-04 | None | 6.75813E-05 | 0 | None | 0 | 1.65125E-04 | 2.71237E-05 | 1.09825E-05 | 3.84172E-04 |
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 | 0.6729 | likely_pathogenic | 0.5687 | pathogenic | -0.207 | Destabilizing | 0.804 | D | 0.613 | neutral | N | 0.479082547 | None | None | N |
| D/C | 0.9615 | likely_pathogenic | 0.9453 | pathogenic | 0.102 | Stabilizing | 0.996 | D | 0.86 | deleterious | None | None | None | None | N |
| D/E | 0.5983 | likely_pathogenic | 0.5195 | ambiguous | -0.271 | Destabilizing | 0.007 | N | 0.366 | neutral | N | 0.476831675 | None | None | N |
| D/F | 0.9639 | likely_pathogenic | 0.9435 | pathogenic | -0.248 | Destabilizing | 0.996 | D | 0.789 | deleterious | None | None | None | None | N |
| D/G | 0.7038 | likely_pathogenic | 0.6091 | pathogenic | -0.36 | Destabilizing | 0.7 | D | 0.74 | deleterious | N | 0.455790565 | None | None | N |
| D/H | 0.822 | likely_pathogenic | 0.7752 | pathogenic | 0.004 | Stabilizing | 0.994 | D | 0.833 | deleterious | N | 0.4630984 | None | None | N |
| D/I | 0.94 | likely_pathogenic | 0.9104 | pathogenic | 0.14 | Stabilizing | 0.956 | D | 0.793 | deleterious | None | None | None | None | N |
| D/K | 0.9312 | likely_pathogenic | 0.9082 | pathogenic | 0.494 | Stabilizing | 0.844 | D | 0.755 | deleterious | None | None | None | None | N |
| D/L | 0.9139 | likely_pathogenic | 0.8726 | pathogenic | 0.14 | Stabilizing | 0.916 | D | 0.728 | deleterious | None | None | None | None | N |
| D/M | 0.9755 | likely_pathogenic | 0.9634 | pathogenic | 0.231 | Stabilizing | 0.996 | D | 0.854 | deleterious | None | None | None | None | N |
| D/N | 0.394 | ambiguous | 0.3821 | ambiguous | 0.202 | Stabilizing | 0.979 | D | 0.785 | deleterious | N | 0.468921297 | None | None | N |
| D/P | 0.92 | likely_pathogenic | 0.8927 | pathogenic | 0.045 | Stabilizing | 0.956 | D | 0.795 | deleterious | None | None | None | None | N |
| D/Q | 0.8695 | likely_pathogenic | 0.8385 | pathogenic | 0.217 | Stabilizing | 0.844 | D | 0.821 | deleterious | None | None | None | None | N |
| D/R | 0.917 | likely_pathogenic | 0.8991 | pathogenic | 0.593 | Stabilizing | 0.916 | D | 0.752 | deleterious | None | None | None | None | N |
| D/S | 0.4717 | ambiguous | 0.3796 | ambiguous | 0.13 | Stabilizing | 0.607 | D | 0.728 | deleterious | None | None | None | None | N |
| D/T | 0.8318 | likely_pathogenic | 0.7584 | pathogenic | 0.254 | Stabilizing | 0.916 | D | 0.791 | deleterious | None | None | None | None | N |
| D/V | 0.8439 | likely_pathogenic | 0.784 | pathogenic | 0.045 | Stabilizing | 0.891 | D | 0.735 | deleterious | N | 0.468160829 | None | None | N |
| D/W | 0.9917 | likely_pathogenic | 0.9897 | pathogenic | -0.15 | Destabilizing | 0.996 | D | 0.818 | deleterious | None | None | None | None | N |
| D/Y | 0.7731 | likely_pathogenic | 0.7126 | pathogenic | -0.015 | Destabilizing | 0.998 | D | 0.795 | deleterious | N | 0.480949166 | 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.