Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16695 | 50308;50309;50310 | chr2:178612442;178612441;178612440 | chr2:179477169;179477168;179477167 |
| N2AB | 15054 | 45385;45386;45387 | chr2:178612442;178612441;178612440 | chr2:179477169;179477168;179477167 |
| N2A | 14127 | 42604;42605;42606 | chr2:178612442;178612441;178612440 | chr2:179477169;179477168;179477167 |
| N2B | 7630 | 23113;23114;23115 | chr2:178612442;178612441;178612440 | chr2:179477169;179477168;179477167 |
| Novex-1 | 7755 | 23488;23489;23490 | chr2:178612442;178612441;178612440 | chr2:179477169;179477168;179477167 |
| Novex-2 | 7822 | 23689;23690;23691 | chr2:178612442;178612441;178612440 | chr2:179477169;179477168;179477167 |
| 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 | rs794729451  |
0.167 | 1.0 | N | 0.647 | 0.283 | None | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.67224E-04 |
| R/Q | rs794729451 |
0.167 | 1.0 | N | 0.647 | 0.283 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07383E-04 | 0 |
| R/Q | rs794729451 |
0.167 | 1.0 | N | 0.647 | 0.283 | None | gnomAD-4.0.0 | 1.05435E-05 | None | None | None | None | N | None | 2.6738E-05 | 0 | None | 0 | 2.24366E-05 | None | 1.56436E-05 | 0 | 8.48028E-06 | 2.19674E-05 | 1.60318E-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 | 0.9686 | likely_pathogenic | 0.9789 | pathogenic | -0.381 | Destabilizing | 0.999 | D | 0.47 | neutral | None | None | None | None | N |
| R/C | 0.8884 | likely_pathogenic | 0.8974 | pathogenic | -0.374 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/D | 0.9882 | likely_pathogenic | 0.9933 | pathogenic | 0.027 | Stabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| R/E | 0.9476 | likely_pathogenic | 0.9731 | pathogenic | 0.11 | Stabilizing | 0.999 | D | 0.519 | neutral | None | None | None | None | N |
| R/F | 0.9802 | likely_pathogenic | 0.9868 | pathogenic | -0.458 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| R/G | 0.9023 | likely_pathogenic | 0.9168 | pathogenic | -0.624 | Destabilizing | 1.0 | D | 0.545 | neutral | N | 0.464338879 | None | None | N |
| R/H | 0.6434 | likely_pathogenic | 0.688 | pathogenic | -1.002 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| R/I | 0.9521 | likely_pathogenic | 0.9726 | pathogenic | 0.242 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| R/K | 0.4486 | ambiguous | 0.4512 | ambiguous | -0.398 | Destabilizing | 0.998 | D | 0.417 | neutral | None | None | None | None | N |
| R/L | 0.8802 | likely_pathogenic | 0.9113 | pathogenic | 0.242 | Stabilizing | 1.0 | D | 0.545 | neutral | D | 0.544244607 | None | None | N |
| R/M | 0.9535 | likely_pathogenic | 0.9713 | pathogenic | -0.078 | Destabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| R/N | 0.9744 | likely_pathogenic | 0.983 | pathogenic | 0.055 | Stabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| R/P | 0.9897 | likely_pathogenic | 0.9937 | pathogenic | 0.056 | Stabilizing | 1.0 | D | 0.64 | neutral | N | 0.515017534 | None | None | N |
| R/Q | 0.594 | likely_pathogenic | 0.6705 | pathogenic | -0.132 | Destabilizing | 1.0 | D | 0.647 | neutral | N | 0.486929927 | None | None | N |
| R/S | 0.9767 | likely_pathogenic | 0.9844 | pathogenic | -0.539 | Destabilizing | 1.0 | D | 0.595 | neutral | None | None | None | None | N |
| R/T | 0.9524 | likely_pathogenic | 0.9699 | pathogenic | -0.303 | Destabilizing | 1.0 | D | 0.598 | neutral | None | None | None | None | N |
| R/V | 0.9548 | likely_pathogenic | 0.9729 | pathogenic | 0.056 | Stabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| R/W | 0.8403 | likely_pathogenic | 0.8812 | pathogenic | -0.305 | Destabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | N |
| R/Y | 0.9535 | likely_pathogenic | 0.9648 | pathogenic | 0.048 | Stabilizing | 1.0 | D | 0.679 | 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.