Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32748 | 98467;98468;98469 | chr2:178539823;178539822;178539821 | chr2:179404550;179404549;179404548 |
| N2AB | 31107 | 93544;93545;93546 | chr2:178539823;178539822;178539821 | chr2:179404550;179404549;179404548 |
| N2A | 30180 | 90763;90764;90765 | chr2:178539823;178539822;178539821 | chr2:179404550;179404549;179404548 |
| N2B | 23683 | 71272;71273;71274 | chr2:178539823;178539822;178539821 | chr2:179404550;179404549;179404548 |
| Novex-1 | 23808 | 71647;71648;71649 | chr2:178539823;178539822;178539821 | chr2:179404550;179404549;179404548 |
| Novex-2 | 23875 | 71848;71849;71850 | chr2:178539823;178539822;178539821 | chr2:179404550;179404549;179404548 |
| 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/C | rs72648272  |
-0.058 | 1.0 | N | 0.717 | 0.354 | None | gnomAD-2.1.1 | 3.97485E-03 | None | None | None | None | N | None | 2.47995E-04 | 5.09338E-04 | None | 1.16032E-03 | 0 | None | 2.74492E-03 | None | 8.83505E-03 | 5.86876E-03 | 2.94448E-03 |
| R/C | rs72648272 |
-0.058 | 1.0 | N | 0.717 | 0.354 | None | gnomAD-3.1.2 | 3.6019E-03 | None | None | None | None | N | None | 5.06806E-04 | 1.17894E-03 | 1.09649E-03 | 1.15274E-03 | 0 | None | 1.05581E-02 | 0 | 5.55637E-03 | 2.69821E-03 | 4.78011E-04 |
| R/C | rs72648272 |
-0.058 | 1.0 | N | 0.717 | 0.354 | None | 1000 genomes | 1.39776E-03 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 2E-03 | None | None | None | 4.1E-03 | None |
| R/C | rs72648272 |
-0.058 | 1.0 | N | 0.717 | 0.354 | None | gnomAD-4.0.0 | 3.45949E-03 | None | None | None | None | N | None | 4.26496E-04 | 7.66616E-04 | None | 8.78319E-04 | 2.22856E-05 | None | 8.96791E-03 | 1.65017E-03 | 3.82105E-03 | 2.22901E-03 | 2.91284E-03 |
| R/H | rs397517775 |
-0.632 | 1.0 | N | 0.706 | 0.338 | None | gnomAD-2.1.1 | 6.42E-05 | None | None | None | None | N | None | 8.26E-05 | 0 | None | 0 | 1.53815E-04 | None | 3.27E-05 | None | 0 | 9.36E-05 | 0 |
| R/H | rs397517775 |
-0.632 | 1.0 | N | 0.706 | 0.338 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 1.92827E-04 | None | 0 | 0 | 1.02896E-04 | 2.07125E-04 | 0 |
| R/H | rs397517775 |
-0.632 | 1.0 | N | 0.706 | 0.338 | None | gnomAD-4.0.0 | 6.19649E-05 | None | None | None | None | N | None | 3.99883E-05 | 0 | None | 0 | 6.68628E-05 | None | 0 | 0 | 7.45902E-05 | 3.29374E-05 | 4.80169E-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 | 0.6269 | likely_pathogenic | 0.671 | pathogenic | -0.288 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | None | N |
| R/C | 0.3663 | ambiguous | 0.3996 | ambiguous | -0.317 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.487921968 | None | None | N |
| R/D | 0.744 | likely_pathogenic | 0.7522 | pathogenic | 0.017 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| R/E | 0.5174 | ambiguous | 0.5362 | ambiguous | 0.113 | Stabilizing | 0.999 | D | 0.619 | neutral | None | None | None | None | N |
| R/F | 0.8105 | likely_pathogenic | 0.839 | pathogenic | -0.359 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/G | 0.5091 | ambiguous | 0.5444 | ambiguous | -0.546 | Destabilizing | 1.0 | D | 0.654 | neutral | N | 0.463270347 | None | None | N |
| R/H | 0.1694 | likely_benign | 0.1764 | benign | -1.034 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | N | 0.490403979 | None | None | N |
| R/I | 0.4871 | ambiguous | 0.5397 | ambiguous | 0.375 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| R/K | 0.1357 | likely_benign | 0.1431 | benign | -0.29 | Destabilizing | 0.998 | D | 0.539 | neutral | None | None | None | None | N |
| R/L | 0.4512 | ambiguous | 0.4973 | ambiguous | 0.375 | Stabilizing | 1.0 | D | 0.654 | neutral | N | 0.475298215 | None | None | N |
| R/M | 0.482 | ambiguous | 0.5436 | ambiguous | -0.027 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| R/N | 0.6507 | likely_pathogenic | 0.6739 | pathogenic | 0.057 | Stabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| R/P | 0.8915 | likely_pathogenic | 0.9111 | pathogenic | 0.176 | Stabilizing | 1.0 | D | 0.655 | neutral | N | 0.487414989 | None | None | N |
| R/Q | 0.1622 | likely_benign | 0.175 | benign | -0.068 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | N |
| R/S | 0.7019 | likely_pathogenic | 0.7324 | pathogenic | -0.483 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | N | 0.51150997 | None | None | N |
| R/T | 0.3811 | ambiguous | 0.4174 | ambiguous | -0.223 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| R/V | 0.5812 | likely_pathogenic | 0.6258 | pathogenic | 0.176 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| R/W | 0.3708 | ambiguous | 0.4051 | ambiguous | -0.247 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| R/Y | 0.5924 | likely_pathogenic | 0.6275 | pathogenic | 0.129 | Stabilizing | 1.0 | D | 0.683 | 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.