Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25321 | 76186;76187;76188 | chr2:178570171;178570170;178570169 | chr2:179434898;179434897;179434896 |
| N2AB | 23680 | 71263;71264;71265 | chr2:178570171;178570170;178570169 | chr2:179434898;179434897;179434896 |
| N2A | 22753 | 68482;68483;68484 | chr2:178570171;178570170;178570169 | chr2:179434898;179434897;179434896 |
| N2B | 16256 | 48991;48992;48993 | chr2:178570171;178570170;178570169 | chr2:179434898;179434897;179434896 |
| Novex-1 | 16381 | 49366;49367;49368 | chr2:178570171;178570170;178570169 | chr2:179434898;179434897;179434896 |
| Novex-2 | 16448 | 49567;49568;49569 | chr2:178570171;178570170;178570169 | chr2:179434898;179434897;179434896 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | rs748102666  |
-1.677 | 0.994 | N | 0.764 | 0.535 | 0.754413127693 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| M/T | rs748102666 |
-1.677 | 0.994 | N | 0.764 | 0.535 | 0.754413127693 | gnomAD-4.0.0 | 9.5803E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73732E-04 | 1.07948E-05 | 0 | 1.65695E-05 |
| M/V | rs769235958 |
-0.705 | 0.985 | N | 0.533 | 0.425 | 0.521070178209 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| M/V | rs769235958 |
-0.705 | 0.985 | N | 0.533 | 0.425 | 0.521070178209 | 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 |
| M/V | rs769235958 |
-0.705 | 0.985 | N | 0.533 | 0.425 | 0.521070178209 | gnomAD-4.0.0 | 8.67728E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.18682E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.7172 | likely_pathogenic | 0.7406 | pathogenic | -2.149 | Highly Destabilizing | 0.989 | D | 0.682 | prob.neutral | None | None | None | None | N |
| M/C | 0.7937 | likely_pathogenic | 0.8342 | pathogenic | -2.612 | Highly Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| M/D | 0.9987 | likely_pathogenic | 0.9989 | pathogenic | -2.19 | Highly Destabilizing | 0.999 | D | 0.802 | deleterious | None | None | None | None | N |
| M/E | 0.9862 | likely_pathogenic | 0.9878 | pathogenic | -1.938 | Destabilizing | 0.999 | D | 0.763 | deleterious | None | None | None | None | N |
| M/F | 0.8556 | likely_pathogenic | 0.8447 | pathogenic | -0.715 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | N |
| M/G | 0.9703 | likely_pathogenic | 0.9736 | pathogenic | -2.638 | Highly Destabilizing | 0.995 | D | 0.741 | deleterious | None | None | None | None | N |
| M/H | 0.9911 | likely_pathogenic | 0.9903 | pathogenic | -2.399 | Highly Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| M/I | 0.7359 | likely_pathogenic | 0.7785 | pathogenic | -0.734 | Destabilizing | 0.985 | D | 0.637 | neutral | N | 0.467260548 | None | None | N |
| M/K | 0.9658 | likely_pathogenic | 0.9598 | pathogenic | -1.362 | Destabilizing | 0.994 | D | 0.763 | deleterious | N | 0.511464862 | None | None | N |
| M/L | 0.4571 | ambiguous | 0.4671 | ambiguous | -0.734 | Destabilizing | 0.927 | D | 0.425 | neutral | N | 0.444244828 | None | None | N |
| M/N | 0.9851 | likely_pathogenic | 0.9865 | pathogenic | -1.837 | Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | N |
| M/P | 0.9994 | likely_pathogenic | 0.9992 | pathogenic | -1.189 | Destabilizing | 0.999 | D | 0.774 | deleterious | None | None | None | None | N |
| M/Q | 0.9016 | likely_pathogenic | 0.9044 | pathogenic | -1.465 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| M/R | 0.9648 | likely_pathogenic | 0.9611 | pathogenic | -1.621 | Destabilizing | 0.998 | D | 0.802 | deleterious | N | 0.499943972 | None | None | N |
| M/S | 0.8994 | likely_pathogenic | 0.9132 | pathogenic | -2.365 | Highly Destabilizing | 0.995 | D | 0.746 | deleterious | None | None | None | None | N |
| M/T | 0.8527 | likely_pathogenic | 0.866 | pathogenic | -1.975 | Destabilizing | 0.994 | D | 0.764 | deleterious | N | 0.499436993 | None | None | N |
| M/V | 0.1966 | likely_benign | 0.2228 | benign | -1.189 | Destabilizing | 0.985 | D | 0.533 | neutral | N | 0.409212322 | None | None | N |
| M/W | 0.9936 | likely_pathogenic | 0.9919 | pathogenic | -1.065 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| M/Y | 0.9862 | likely_pathogenic | 0.9846 | pathogenic | -1.02 | Destabilizing | 0.999 | D | 0.801 | deleterious | None | None | 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.