Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32077 | 96454;96455;96456 | chr2:178543915;178543914;178543913 | chr2:179408642;179408641;179408640 |
| N2AB | 30436 | 91531;91532;91533 | chr2:178543915;178543914;178543913 | chr2:179408642;179408641;179408640 |
| N2A | 29509 | 88750;88751;88752 | chr2:178543915;178543914;178543913 | chr2:179408642;179408641;179408640 |
| N2B | 23012 | 69259;69260;69261 | chr2:178543915;178543914;178543913 | chr2:179408642;179408641;179408640 |
| Novex-1 | 23137 | 69634;69635;69636 | chr2:178543915;178543914;178543913 | chr2:179408642;179408641;179408640 |
| Novex-2 | 23204 | 69835;69836;69837 | chr2:178543915;178543914;178543913 | chr2:179408642;179408641;179408640 |
| 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/Q | rs369835255  |
0.207 | 1.0 | N | 0.707 | 0.37 | None | gnomAD-2.1.1 | 3.21E-05 | None | None | None | None | I | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.46E-05 | 0 |
| R/Q | rs369835255 |
0.207 | 1.0 | N | 0.707 | 0.37 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 9.67E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 4.16146E-04 | 0 |
| R/Q | rs369835255 |
0.207 | 1.0 | N | 0.707 | 0.37 | None | gnomAD-4.0.0 | 2.479E-05 | None | None | None | None | I | None | 5.33589E-05 | 0 | None | 0 | 0 | None | 0 | 1.65125E-04 | 2.62784E-05 | 4.39309E-05 | 0 |
| R/W | rs751316145 |
-0.36 | 1.0 | N | 0.769 | 0.5 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.13E-05 | None | 3.27E-05 | None | 0 | 7.81E-06 | 0 |
| R/W | rs751316145 |
-0.36 | 1.0 | N | 0.769 | 0.5 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs751316145 |
-0.36 | 1.0 | N | 0.769 | 0.5 | None | gnomAD-4.0.0 | 5.5781E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.22866E-05 | None | 0 | 0 | 3.39073E-06 | 3.29446E-05 | 1.60143E-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 | 0.9816 | likely_pathogenic | 0.9692 | pathogenic | -0.035 | Destabilizing | 0.999 | D | 0.628 | neutral | None | None | None | None | I |
| R/C | 0.8023 | likely_pathogenic | 0.7037 | pathogenic | -0.169 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| R/D | 0.9972 | likely_pathogenic | 0.9951 | pathogenic | -0.138 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | I |
| R/E | 0.9754 | likely_pathogenic | 0.9614 | pathogenic | -0.044 | Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | I |
| R/F | 0.9923 | likely_pathogenic | 0.9872 | pathogenic | -0.167 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | I |
| R/G | 0.9758 | likely_pathogenic | 0.958 | pathogenic | -0.262 | Destabilizing | 1.0 | D | 0.587 | neutral | N | 0.517944598 | None | None | I |
| R/H | 0.6807 | likely_pathogenic | 0.5777 | pathogenic | -0.953 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| R/I | 0.9458 | likely_pathogenic | 0.9158 | pathogenic | 0.539 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| R/K | 0.4882 | ambiguous | 0.4236 | ambiguous | -0.084 | Destabilizing | 0.998 | D | 0.565 | neutral | None | None | None | None | I |
| R/L | 0.94 | likely_pathogenic | 0.9018 | pathogenic | 0.539 | Stabilizing | 1.0 | D | 0.587 | neutral | N | 0.460816995 | None | None | I |
| R/M | 0.972 | likely_pathogenic | 0.9507 | pathogenic | -0.026 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| R/N | 0.9925 | likely_pathogenic | 0.9876 | pathogenic | 0.058 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| R/P | 0.9886 | likely_pathogenic | 0.981 | pathogenic | 0.369 | Stabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.452614241 | None | None | I |
| R/Q | 0.6653 | likely_pathogenic | 0.5767 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.481963124 | None | None | I |
| R/S | 0.99 | likely_pathogenic | 0.9833 | pathogenic | -0.244 | Destabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | I |
| R/T | 0.9817 | likely_pathogenic | 0.9695 | pathogenic | 0.003 | Stabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | I |
| R/V | 0.966 | likely_pathogenic | 0.9481 | pathogenic | 0.369 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| R/W | 0.8997 | likely_pathogenic | 0.8371 | pathogenic | -0.234 | Destabilizing | 1.0 | D | 0.769 | deleterious | N | 0.503309836 | None | None | I |
| R/Y | 0.9665 | likely_pathogenic | 0.9437 | pathogenic | 0.169 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | 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.