Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2122 | 6589;6590;6591 | chr2:178775500;178775499;178775498 | chr2:179640227;179640226;179640225 |
| N2AB | 2122 | 6589;6590;6591 | chr2:178775500;178775499;178775498 | chr2:179640227;179640226;179640225 |
| N2A | 2122 | 6589;6590;6591 | chr2:178775500;178775499;178775498 | chr2:179640227;179640226;179640225 |
| N2B | 2076 | 6451;6452;6453 | chr2:178775500;178775499;178775498 | chr2:179640227;179640226;179640225 |
| Novex-1 | 2076 | 6451;6452;6453 | chr2:178775500;178775499;178775498 | chr2:179640227;179640226;179640225 |
| Novex-2 | 2076 | 6451;6452;6453 | chr2:178775500;178775499;178775498 | chr2:179640227;179640226;179640225 |
| Novex-3 | 2122 | 6589;6590;6591 | chr2:178775500;178775499;178775498 | chr2:179640227;179640226;179640225 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs2092123649  |
None | 0.767 | N | 0.31 | 0.441 | 0.480801007081 | 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 |
| D/E | rs2092123649 |
None | 0.767 | N | 0.31 | 0.441 | 0.480801007081 | gnomAD-4.0.0 | 6.57341E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46998E-05 | 0 | 0 |
| D/H | rs748790571 |
0.639 | 1.0 | D | 0.689 | 0.74 | 0.527455595252 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 9.93E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs748790571 |
0.639 | 1.0 | D | 0.689 | 0.74 | 0.527455595252 | gnomAD-4.0.0 | 1.59079E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.7669E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3421 | ambiguous | 0.3377 | benign | 0.002 | Stabilizing | 0.996 | D | 0.527 | neutral | D | 0.532870174 | None | None | N |
| D/C | 0.8801 | likely_pathogenic | 0.8797 | pathogenic | -0.11 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| D/E | 0.1623 | likely_benign | 0.1709 | benign | -0.236 | Destabilizing | 0.767 | D | 0.31 | neutral | N | 0.499184072 | None | None | N |
| D/F | 0.8697 | likely_pathogenic | 0.8658 | pathogenic | 0.061 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| D/G | 0.3183 | likely_benign | 0.3065 | benign | -0.144 | Destabilizing | 0.998 | D | 0.592 | neutral | D | 0.524865151 | None | None | N |
| D/H | 0.5507 | ambiguous | 0.5436 | ambiguous | 0.593 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | D | 0.603685791 | None | None | N |
| D/I | 0.7324 | likely_pathogenic | 0.724 | pathogenic | 0.326 | Stabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| D/K | 0.6044 | likely_pathogenic | 0.5891 | pathogenic | 0.528 | Stabilizing | 0.999 | D | 0.612 | neutral | None | None | None | None | N |
| D/L | 0.6727 | likely_pathogenic | 0.6625 | pathogenic | 0.326 | Stabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| D/M | 0.8298 | likely_pathogenic | 0.8241 | pathogenic | 0.144 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/N | 0.1582 | likely_benign | 0.1515 | benign | 0.109 | Stabilizing | 0.999 | D | 0.659 | neutral | D | 0.525789264 | None | None | N |
| D/P | 0.6165 | likely_pathogenic | 0.6261 | pathogenic | 0.238 | Stabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| D/Q | 0.5016 | ambiguous | 0.4918 | ambiguous | 0.155 | Stabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| D/R | 0.6684 | likely_pathogenic | 0.6615 | pathogenic | 0.759 | Stabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| D/S | 0.1838 | likely_benign | 0.1797 | benign | 0.054 | Stabilizing | 0.997 | D | 0.583 | neutral | None | None | None | None | N |
| D/T | 0.4584 | ambiguous | 0.4486 | ambiguous | 0.184 | Stabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | N |
| D/V | 0.54 | ambiguous | 0.5332 | ambiguous | 0.238 | Stabilizing | 0.999 | D | 0.671 | neutral | D | 0.650411948 | None | None | N |
| D/W | 0.9613 | likely_pathogenic | 0.961 | pathogenic | 0.149 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/Y | 0.5921 | likely_pathogenic | 0.58 | pathogenic | 0.3 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | D | 0.650655203 | 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.