Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27730 | 83413;83414;83415 | chr2:178562944;178562943;178562942 | chr2:179427671;179427670;179427669 |
| N2AB | 26089 | 78490;78491;78492 | chr2:178562944;178562943;178562942 | chr2:179427671;179427670;179427669 |
| N2A | 25162 | 75709;75710;75711 | chr2:178562944;178562943;178562942 | chr2:179427671;179427670;179427669 |
| N2B | 18665 | 56218;56219;56220 | chr2:178562944;178562943;178562942 | chr2:179427671;179427670;179427669 |
| Novex-1 | 18790 | 56593;56594;56595 | chr2:178562944;178562943;178562942 | chr2:179427671;179427670;179427669 |
| Novex-2 | 18857 | 56794;56795;56796 | chr2:178562944;178562943;178562942 | chr2:179427671;179427670;179427669 |
| 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/I | rs1229835465  |
-0.533 | 0.521 | N | 0.393 | 0.279 | 0.579627256647 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| M/I | rs1229835465 |
-0.533 | 0.521 | N | 0.393 | 0.279 | 0.579627256647 | gnomAD-4.0.0 | 6.8427E-07 | None | None | None | None | I | None | 2.98864E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | None | None | 0.815 | N | 0.472 | 0.336 | 0.663846892577 | gnomAD-4.0.0 | 1.59161E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85865E-06 | 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 | 0.5067 | ambiguous | 0.5249 | ambiguous | -2.238 | Highly Destabilizing | 0.373 | N | 0.441 | neutral | None | None | None | None | I |
| M/C | 0.7223 | likely_pathogenic | 0.7304 | pathogenic | -2.179 | Highly Destabilizing | 0.996 | D | 0.544 | neutral | None | None | None | None | I |
| M/D | 0.9629 | likely_pathogenic | 0.9644 | pathogenic | -2.048 | Highly Destabilizing | 0.953 | D | 0.611 | neutral | None | None | None | None | I |
| M/E | 0.7859 | likely_pathogenic | 0.7906 | pathogenic | -1.797 | Destabilizing | 0.947 | D | 0.605 | neutral | None | None | None | None | I |
| M/F | 0.6114 | likely_pathogenic | 0.6117 | pathogenic | -0.767 | Destabilizing | 0.009 | N | 0.2 | neutral | None | None | None | None | I |
| M/G | 0.7914 | likely_pathogenic | 0.7964 | pathogenic | -2.729 | Highly Destabilizing | 0.004 | N | 0.373 | neutral | None | None | None | None | I |
| M/H | 0.7002 | likely_pathogenic | 0.7016 | pathogenic | -2.39 | Highly Destabilizing | 0.996 | D | 0.601 | neutral | None | None | None | None | I |
| M/I | 0.6694 | likely_pathogenic | 0.7263 | pathogenic | -0.815 | Destabilizing | 0.521 | D | 0.393 | neutral | N | 0.415867014 | None | None | I |
| M/K | 0.4944 | ambiguous | 0.5281 | ambiguous | -1.455 | Destabilizing | 0.815 | D | 0.523 | neutral | N | 0.439626521 | None | None | I |
| M/L | 0.1753 | likely_benign | 0.2047 | benign | -0.815 | Destabilizing | 0.164 | N | 0.283 | neutral | N | 0.394240948 | None | None | I |
| M/N | 0.7168 | likely_pathogenic | 0.7225 | pathogenic | -1.879 | Destabilizing | 0.953 | D | 0.622 | neutral | None | None | None | None | I |
| M/P | 0.9951 | likely_pathogenic | 0.9962 | pathogenic | -1.273 | Destabilizing | 0.984 | D | 0.621 | neutral | None | None | None | None | I |
| M/Q | 0.3733 | ambiguous | 0.3686 | ambiguous | -1.53 | Destabilizing | 0.984 | D | 0.509 | neutral | None | None | None | None | I |
| M/R | 0.5077 | ambiguous | 0.5373 | ambiguous | -1.576 | Destabilizing | 0.979 | D | 0.588 | neutral | N | 0.447515286 | None | None | I |
| M/S | 0.3929 | ambiguous | 0.3887 | ambiguous | -2.428 | Highly Destabilizing | 0.742 | D | 0.476 | neutral | None | None | None | None | I |
| M/T | 0.2748 | likely_benign | 0.2991 | benign | -2.048 | Highly Destabilizing | 0.815 | D | 0.472 | neutral | N | 0.362624388 | None | None | I |
| M/V | 0.1668 | likely_benign | 0.1887 | benign | -1.273 | Destabilizing | 0.472 | N | 0.459 | neutral | N | 0.422254269 | None | None | I |
| M/W | 0.895 | likely_pathogenic | 0.9022 | pathogenic | -1.129 | Destabilizing | 0.996 | D | 0.542 | neutral | None | None | None | None | I |
| M/Y | 0.7729 | likely_pathogenic | 0.7777 | pathogenic | -1.097 | Destabilizing | 0.835 | D | 0.556 | neutral | 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.