Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25431 | 76516;76517;76518 | chr2:178569841;178569840;178569839 | chr2:179434568;179434567;179434566 |
| N2AB | 23790 | 71593;71594;71595 | chr2:178569841;178569840;178569839 | chr2:179434568;179434567;179434566 |
| N2A | 22863 | 68812;68813;68814 | chr2:178569841;178569840;178569839 | chr2:179434568;179434567;179434566 |
| N2B | 16366 | 49321;49322;49323 | chr2:178569841;178569840;178569839 | chr2:179434568;179434567;179434566 |
| Novex-1 | 16491 | 49696;49697;49698 | chr2:178569841;178569840;178569839 | chr2:179434568;179434567;179434566 |
| Novex-2 | 16558 | 49897;49898;49899 | chr2:178569841;178569840;178569839 | chr2:179434568;179434567;179434566 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs79906856  |
0.324 | 1.0 | N | 0.675 | 0.518 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.23289E-04 | None | 0 | None | 0 | 0 | 0 |
| Y/C | rs79906856 |
0.324 | 1.0 | N | 0.675 | 0.518 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 3.86847E-04 | None | 0 | 0 | 0 | 0 | 0 |
| Y/C | rs79906856 |
0.324 | 1.0 | N | 0.675 | 0.518 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| Y/C | rs79906856 |
0.324 | 1.0 | N | 0.675 | 0.518 | None | gnomAD-4.0.0 | 1.61139E-05 | None | None | None | None | I | None | 0 | 1.66728E-05 | None | 0 | 5.35499E-04 | None | 0 | 0 | 8.47719E-07 | 0 | 0 |
| Y/H | None | None | 1.0 | N | 0.661 | 0.434 | 0.275215494804 | gnomAD-4.0.0 | 8.21181E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.07947E-05 | 0 | 0 |
| Y/N | rs1488563673 |
0.157 | 1.0 | N | 0.667 | 0.516 | 0.471211772063 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/N | rs1488563673 |
0.157 | 1.0 | N | 0.667 | 0.516 | 0.471211772063 | gnomAD-4.0.0 | 6.84317E-07 | None | None | None | None | I | None | 2.98936E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.8991 | likely_pathogenic | 0.8815 | pathogenic | -0.866 | Destabilizing | 1.0 | D | 0.565 | neutral | None | None | None | None | I |
| Y/C | 0.4711 | ambiguous | 0.4512 | ambiguous | 0.015 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | N | 0.475149041 | None | None | I |
| Y/D | 0.8144 | likely_pathogenic | 0.7599 | pathogenic | 0.911 | Stabilizing | 1.0 | D | 0.668 | neutral | N | 0.447527489 | None | None | I |
| Y/E | 0.9566 | likely_pathogenic | 0.9491 | pathogenic | 0.897 | Stabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| Y/F | 0.2026 | likely_benign | 0.2182 | benign | -0.433 | Destabilizing | 0.999 | D | 0.504 | neutral | N | 0.455270359 | None | None | I |
| Y/G | 0.8349 | likely_pathogenic | 0.7988 | pathogenic | -1.062 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| Y/H | 0.6158 | likely_pathogenic | 0.5578 | ambiguous | 0.112 | Stabilizing | 1.0 | D | 0.661 | neutral | N | 0.451004398 | None | None | I |
| Y/I | 0.9105 | likely_pathogenic | 0.9041 | pathogenic | -0.369 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | I |
| Y/K | 0.9394 | likely_pathogenic | 0.9259 | pathogenic | 0.089 | Stabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| Y/L | 0.8256 | likely_pathogenic | 0.8053 | pathogenic | -0.369 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | I |
| Y/M | 0.9126 | likely_pathogenic | 0.9031 | pathogenic | -0.158 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| Y/N | 0.6772 | likely_pathogenic | 0.5279 | ambiguous | -0.098 | Destabilizing | 1.0 | D | 0.667 | neutral | N | 0.484123007 | None | None | I |
| Y/P | 0.9866 | likely_pathogenic | 0.9832 | pathogenic | -0.515 | Destabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | I |
| Y/Q | 0.9216 | likely_pathogenic | 0.9049 | pathogenic | -0.066 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| Y/R | 0.8323 | likely_pathogenic | 0.805 | pathogenic | 0.397 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| Y/S | 0.6243 | likely_pathogenic | 0.5486 | ambiguous | -0.576 | Destabilizing | 1.0 | D | 0.659 | neutral | N | 0.441678952 | None | None | I |
| Y/T | 0.8723 | likely_pathogenic | 0.8366 | pathogenic | -0.5 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| Y/V | 0.8435 | likely_pathogenic | 0.8299 | pathogenic | -0.515 | Destabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | I |
| Y/W | 0.6505 | likely_pathogenic | 0.6421 | pathogenic | -0.492 | Destabilizing | 1.0 | D | 0.644 | 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.