Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25170 | 75733;75734;75735 | chr2:178570624;178570623;178570622 | chr2:179435351;179435350;179435349 |
| N2AB | 23529 | 70810;70811;70812 | chr2:178570624;178570623;178570622 | chr2:179435351;179435350;179435349 |
| N2A | 22602 | 68029;68030;68031 | chr2:178570624;178570623;178570622 | chr2:179435351;179435350;179435349 |
| N2B | 16105 | 48538;48539;48540 | chr2:178570624;178570623;178570622 | chr2:179435351;179435350;179435349 |
| Novex-1 | 16230 | 48913;48914;48915 | chr2:178570624;178570623;178570622 | chr2:179435351;179435350;179435349 |
| Novex-2 | 16297 | 49114;49115;49116 | chr2:178570624;178570623;178570622 | chr2:179435351;179435350;179435349 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/I | rs1355222139  |
0.072 | 0.003 | N | 0.447 | 0.311 | 0.375861065471 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/I | rs1355222139 |
0.072 | 0.003 | N | 0.447 | 0.311 | 0.375861065471 | gnomAD-4.0.0 | 3.18383E-06 | None | None | None | None | N | None | 0 | 4.57415E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/R | rs775835843 |
-0.205 | 0.427 | N | 0.542 | 0.329 | 0.143124449307 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| S/R | rs775835843 |
-0.205 | 0.427 | N | 0.542 | 0.329 | 0.143124449307 | gnomAD-4.0.0 | 6.84329E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99569E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0738 | likely_benign | 0.0706 | benign | -0.986 | Destabilizing | 0.025 | N | 0.357 | neutral | None | None | None | None | N |
| S/C | 0.0642 | likely_benign | 0.0767 | benign | -0.653 | Destabilizing | 0.946 | D | 0.487 | neutral | N | 0.517724732 | None | None | N |
| S/D | 0.3366 | likely_benign | 0.4345 | ambiguous | -0.742 | Destabilizing | 0.124 | N | 0.453 | neutral | None | None | None | None | N |
| S/E | 0.3775 | ambiguous | 0.4679 | ambiguous | -0.597 | Destabilizing | 0.22 | N | 0.453 | neutral | None | None | None | None | N |
| S/F | 0.1045 | likely_benign | 0.0981 | benign | -0.838 | Destabilizing | 0.497 | N | 0.539 | neutral | None | None | None | None | N |
| S/G | 0.1019 | likely_benign | 0.1296 | benign | -1.34 | Destabilizing | None | N | 0.245 | neutral | D | 0.528421729 | None | None | N |
| S/H | 0.1714 | likely_benign | 0.238 | benign | -1.55 | Destabilizing | 0.497 | N | 0.496 | neutral | None | None | None | None | N |
| S/I | 0.0737 | likely_benign | 0.077 | benign | -0.103 | Destabilizing | 0.003 | N | 0.447 | neutral | N | 0.400436202 | None | None | N |
| S/K | 0.4644 | ambiguous | 0.6167 | pathogenic | -0.232 | Destabilizing | 0.124 | N | 0.443 | neutral | None | None | None | None | N |
| S/L | 0.0665 | likely_benign | 0.061 | benign | -0.103 | Destabilizing | 0.055 | N | 0.446 | neutral | None | None | None | None | N |
| S/M | 0.1103 | likely_benign | 0.1126 | benign | -0.17 | Destabilizing | 0.025 | N | 0.384 | neutral | None | None | None | None | N |
| S/N | 0.1081 | likely_benign | 0.1337 | benign | -0.636 | Destabilizing | 0.001 | N | 0.286 | neutral | N | 0.480033136 | None | None | N |
| S/P | 0.8593 | likely_pathogenic | 0.893 | pathogenic | -0.364 | Destabilizing | 0.667 | D | 0.537 | neutral | None | None | None | None | N |
| S/Q | 0.3195 | likely_benign | 0.4196 | ambiguous | -0.547 | Destabilizing | 0.497 | N | 0.501 | neutral | None | None | None | None | N |
| S/R | 0.3745 | ambiguous | 0.5118 | ambiguous | -0.46 | Destabilizing | 0.427 | N | 0.542 | neutral | N | 0.446360492 | None | None | N |
| S/T | 0.0624 | likely_benign | 0.0609 | benign | -0.502 | Destabilizing | 0.081 | N | 0.447 | neutral | N | 0.38544532 | None | None | N |
| S/V | 0.0932 | likely_benign | 0.0953 | benign | -0.364 | Destabilizing | 0.004 | N | 0.437 | neutral | None | None | None | None | N |
| S/W | 0.1825 | likely_benign | 0.2055 | benign | -0.9 | Destabilizing | 0.958 | D | 0.57 | neutral | None | None | None | None | N |
| S/Y | 0.1022 | likely_benign | 0.1118 | benign | -0.533 | Destabilizing | 0.859 | D | 0.515 | 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.