Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1594 | 5005;5006;5007 | chr2:178777183;178777182;178777181 | chr2:179641910;179641909;179641908 |
| N2AB | 1594 | 5005;5006;5007 | chr2:178777183;178777182;178777181 | chr2:179641910;179641909;179641908 |
| N2A | 1594 | 5005;5006;5007 | chr2:178777183;178777182;178777181 | chr2:179641910;179641909;179641908 |
| N2B | 1548 | 4867;4868;4869 | chr2:178777183;178777182;178777181 | chr2:179641910;179641909;179641908 |
| Novex-1 | 1548 | 4867;4868;4869 | chr2:178777183;178777182;178777181 | chr2:179641910;179641909;179641908 |
| Novex-2 | 1548 | 4867;4868;4869 | chr2:178777183;178777182;178777181 | chr2:179641910;179641909;179641908 |
| Novex-3 | 1594 | 5005;5006;5007 | chr2:178777183;178777182;178777181 | chr2:179641910;179641909;179641908 |
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 | rs2092324432  |
None | 0.974 | N | 0.677 | 0.451 | 0.408579541211 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/H | rs2092324432 |
None | 0.974 | N | 0.677 | 0.451 | 0.408579541211 | gnomAD-4.0.0 | 6.56987E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46981E-05 | 0 | 0 |
| D/V | rs1024757348 |
0.243 | 0.83 | N | 0.718 | 0.565 | 0.533083562301 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.81E-06 | 0 |
| D/V | rs1024757348 |
0.243 | 0.83 | N | 0.718 | 0.565 | 0.533083562301 | gnomAD-4.0.0 | 9.57735E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.25906E-05 | 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 | 0.4852 | ambiguous | 0.4135 | ambiguous | -0.194 | Destabilizing | 0.41 | N | 0.609 | neutral | N | 0.495736434 | None | None | N |
| D/C | 0.943 | likely_pathogenic | 0.914 | pathogenic | -0.087 | Destabilizing | 0.993 | D | 0.673 | neutral | None | None | None | None | N |
| D/E | 0.1776 | likely_benign | 0.1417 | benign | -0.486 | Destabilizing | 0.004 | N | 0.263 | neutral | N | 0.478358811 | None | None | N |
| D/F | 0.9517 | likely_pathogenic | 0.9242 | pathogenic | 0.476 | Stabilizing | 0.993 | D | 0.7 | prob.neutral | None | None | None | None | N |
| D/G | 0.6368 | likely_pathogenic | 0.5374 | ambiguous | -0.553 | Destabilizing | 0.581 | D | 0.623 | neutral | N | 0.50013182 | None | None | N |
| D/H | 0.761 | likely_pathogenic | 0.6959 | pathogenic | 0.463 | Stabilizing | 0.974 | D | 0.677 | prob.neutral | N | 0.507482686 | None | None | N |
| D/I | 0.8341 | likely_pathogenic | 0.7544 | pathogenic | 0.75 | Stabilizing | 0.929 | D | 0.725 | prob.delet. | None | None | None | None | N |
| D/K | 0.8091 | likely_pathogenic | 0.7241 | pathogenic | 0.17 | Stabilizing | 0.764 | D | 0.653 | neutral | None | None | None | None | N |
| D/L | 0.85 | likely_pathogenic | 0.7745 | pathogenic | 0.75 | Stabilizing | 0.866 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/M | 0.9119 | likely_pathogenic | 0.8633 | pathogenic | 0.932 | Stabilizing | 0.993 | D | 0.677 | prob.neutral | None | None | None | None | N |
| D/N | 0.2613 | likely_benign | 0.2146 | benign | -0.599 | Destabilizing | 0.83 | D | 0.586 | neutral | N | 0.501375552 | None | None | N |
| D/P | 0.9939 | likely_pathogenic | 0.9867 | pathogenic | 0.461 | Stabilizing | 0.929 | D | 0.682 | prob.neutral | None | None | None | None | N |
| D/Q | 0.6745 | likely_pathogenic | 0.5821 | pathogenic | -0.406 | Destabilizing | 0.764 | D | 0.653 | neutral | None | None | None | None | N |
| D/R | 0.8577 | likely_pathogenic | 0.7947 | pathogenic | 0.439 | Stabilizing | 0.764 | D | 0.684 | prob.neutral | None | None | None | None | N |
| D/S | 0.36 | ambiguous | 0.2961 | benign | -0.752 | Destabilizing | 0.48 | N | 0.564 | neutral | None | None | None | None | N |
| D/T | 0.6072 | likely_pathogenic | 0.517 | ambiguous | -0.432 | Destabilizing | 0.866 | D | 0.665 | neutral | None | None | None | None | N |
| D/V | 0.651 | likely_pathogenic | 0.5503 | ambiguous | 0.461 | Stabilizing | 0.83 | D | 0.718 | prob.delet. | N | 0.473552143 | None | None | N |
| D/W | 0.9893 | likely_pathogenic | 0.9821 | pathogenic | 0.725 | Stabilizing | 0.993 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/Y | 0.7718 | likely_pathogenic | 0.674 | pathogenic | 0.771 | Stabilizing | 0.991 | D | 0.699 | prob.neutral | N | 0.511578919 | 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.