Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25932 | 78019;78020;78021 | chr2:178568338;178568337;178568336 | chr2:179433065;179433064;179433063 |
| N2AB | 24291 | 73096;73097;73098 | chr2:178568338;178568337;178568336 | chr2:179433065;179433064;179433063 |
| N2A | 23364 | 70315;70316;70317 | chr2:178568338;178568337;178568336 | chr2:179433065;179433064;179433063 |
| N2B | 16867 | 50824;50825;50826 | chr2:178568338;178568337;178568336 | chr2:179433065;179433064;179433063 |
| Novex-1 | 16992 | 51199;51200;51201 | chr2:178568338;178568337;178568336 | chr2:179433065;179433064;179433063 |
| Novex-2 | 17059 | 51400;51401;51402 | chr2:178568338;178568337;178568336 | chr2:179433065;179433064;179433063 |
| 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 | None | None | 1.0 | N | 0.427 | 0.182 | 0.21279746466 | gnomAD-4.0.0 | 1.36874E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.7343E-04 | 8.99586E-07 | 0 | 0 |
| D/G | None | None | 1.0 | N | 0.703 | 0.512 | 0.297718772494 | gnomAD-4.0.0 | 1.59211E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43283E-05 | 0 |
| D/N | rs778532395  |
-0.815 | 1.0 | N | 0.605 | 0.406 | 0.354610295913 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 5.81E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66389E-04 |
| D/N | rs778532395 |
-0.815 | 1.0 | N | 0.605 | 0.406 | 0.354610295913 | gnomAD-4.0.0 | 2.73748E-06 | None | None | None | None | N | None | 0 | 6.71261E-05 | None | 0 | 2.52589E-05 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | None | None | 1.0 | D | 0.783 | 0.549 | 0.75727360634 | gnomAD-4.0.0 | 6.8437E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99586E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.5207 | ambiguous | 0.5422 | ambiguous | -0.543 | Destabilizing | 1.0 | D | 0.742 | deleterious | N | 0.479660444 | None | None | N |
| D/C | 0.8129 | likely_pathogenic | 0.8302 | pathogenic | -0.289 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| D/E | 0.2659 | likely_benign | 0.2782 | benign | -0.894 | Destabilizing | 1.0 | D | 0.427 | neutral | N | 0.436900355 | None | None | N |
| D/F | 0.9403 | likely_pathogenic | 0.9538 | pathogenic | -0.456 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| D/G | 0.6849 | likely_pathogenic | 0.7402 | pathogenic | -0.889 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.477876471 | None | None | N |
| D/H | 0.79 | likely_pathogenic | 0.8045 | pathogenic | -0.882 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.496803647 | None | None | N |
| D/I | 0.7994 | likely_pathogenic | 0.8244 | pathogenic | 0.367 | Stabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| D/K | 0.8942 | likely_pathogenic | 0.8957 | pathogenic | -0.623 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| D/L | 0.7728 | likely_pathogenic | 0.7805 | pathogenic | 0.367 | Stabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| D/M | 0.8931 | likely_pathogenic | 0.9087 | pathogenic | 0.888 | Stabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| D/N | 0.2571 | likely_benign | 0.2928 | benign | -0.958 | Destabilizing | 1.0 | D | 0.605 | neutral | N | 0.481800037 | None | None | N |
| D/P | 0.9456 | likely_pathogenic | 0.9535 | pathogenic | 0.089 | Stabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| D/Q | 0.7937 | likely_pathogenic | 0.8084 | pathogenic | -0.815 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| D/R | 0.927 | likely_pathogenic | 0.9278 | pathogenic | -0.561 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| D/S | 0.4574 | ambiguous | 0.5012 | ambiguous | -1.244 | Destabilizing | 1.0 | D | 0.632 | neutral | None | None | None | None | N |
| D/T | 0.7372 | likely_pathogenic | 0.7734 | pathogenic | -0.961 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| D/V | 0.6166 | likely_pathogenic | 0.643 | pathogenic | 0.089 | Stabilizing | 1.0 | D | 0.827 | deleterious | N | 0.496803647 | None | None | N |
| D/W | 0.9897 | likely_pathogenic | 0.9912 | pathogenic | -0.421 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| D/Y | 0.7074 | likely_pathogenic | 0.7431 | pathogenic | -0.262 | Destabilizing | 1.0 | D | 0.783 | deleterious | D | 0.527278165 | 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.