Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1854 | 5785;5786;5787 | chr2:178776304;178776303;178776302 | chr2:179641031;179641030;179641029 |
| N2AB | 1854 | 5785;5786;5787 | chr2:178776304;178776303;178776302 | chr2:179641031;179641030;179641029 |
| N2A | 1854 | 5785;5786;5787 | chr2:178776304;178776303;178776302 | chr2:179641031;179641030;179641029 |
| N2B | 1808 | 5647;5648;5649 | chr2:178776304;178776303;178776302 | chr2:179641031;179641030;179641029 |
| Novex-1 | 1808 | 5647;5648;5649 | chr2:178776304;178776303;178776302 | chr2:179641031;179641030;179641029 |
| Novex-2 | 1808 | 5647;5648;5649 | chr2:178776304;178776303;178776302 | chr2:179641031;179641030;179641029 |
| Novex-3 | 1854 | 5785;5786;5787 | chr2:178776304;178776303;178776302 | chr2:179641031;179641030;179641029 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | rs571222694  |
-0.198 | 0.999 | N | 0.458 | 0.175 | 0.257786959452 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| E/D | rs571222694 |
-0.198 | 0.999 | N | 0.458 | 0.175 | 0.257786959452 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07211E-04 | 0 |
| E/D | rs571222694 |
-0.198 | 0.999 | N | 0.458 | 0.175 | 0.257786959452 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| E/D | rs571222694 |
-0.198 | 0.999 | N | 0.458 | 0.175 | 0.257786959452 | gnomAD-4.0.0 | 6.5653E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| E/K | rs1443747233 |
0.553 | 0.999 | N | 0.608 | 0.315 | 0.27479166964 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| E/K | rs1443747233 |
0.553 | 0.999 | N | 0.608 | 0.315 | 0.27479166964 | gnomAD-4.0.0 | 1.5907E-06 | None | None | None | None | N | None | 0 | 2.28655E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.7947 | likely_pathogenic | 0.7642 | pathogenic | -0.802 | Destabilizing | 0.999 | D | 0.618 | neutral | N | 0.422160002 | None | None | N |
| E/C | 0.9955 | likely_pathogenic | 0.9956 | pathogenic | -0.178 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| E/D | 0.8177 | likely_pathogenic | 0.7707 | pathogenic | -0.641 | Destabilizing | 0.999 | D | 0.458 | neutral | N | 0.455722518 | None | None | N |
| E/F | 0.9972 | likely_pathogenic | 0.9963 | pathogenic | -0.533 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| E/G | 0.9068 | likely_pathogenic | 0.8916 | pathogenic | -1.062 | Destabilizing | 1.0 | D | 0.63 | neutral | D | 0.605950942 | None | None | N |
| E/H | 0.9866 | likely_pathogenic | 0.9847 | pathogenic | -0.567 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| E/I | 0.965 | likely_pathogenic | 0.9579 | pathogenic | -0.122 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| E/K | 0.9466 | likely_pathogenic | 0.9336 | pathogenic | 0.026 | Stabilizing | 0.999 | D | 0.608 | neutral | N | 0.504170164 | None | None | N |
| E/L | 0.9752 | likely_pathogenic | 0.9673 | pathogenic | -0.122 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| E/M | 0.9788 | likely_pathogenic | 0.9744 | pathogenic | 0.23 | Stabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | N |
| E/N | 0.9697 | likely_pathogenic | 0.9634 | pathogenic | -0.405 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| E/P | 0.9733 | likely_pathogenic | 0.9752 | pathogenic | -0.328 | Destabilizing | 1.0 | D | 0.644 | neutral | None | None | None | None | N |
| E/Q | 0.793 | likely_pathogenic | 0.7733 | pathogenic | -0.356 | Destabilizing | 1.0 | D | 0.627 | neutral | N | 0.461127606 | None | None | N |
| E/R | 0.9538 | likely_pathogenic | 0.9482 | pathogenic | 0.208 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| E/S | 0.9038 | likely_pathogenic | 0.8864 | pathogenic | -0.606 | Destabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | N |
| E/T | 0.9395 | likely_pathogenic | 0.9257 | pathogenic | -0.388 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| E/V | 0.9053 | likely_pathogenic | 0.8839 | pathogenic | -0.328 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | N | 0.431408384 | None | None | N |
| E/W | 0.999 | likely_pathogenic | 0.9988 | pathogenic | -0.281 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| E/Y | 0.9943 | likely_pathogenic | 0.9931 | pathogenic | -0.265 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | 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.