Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32233 | 96922;96923;96924 | chr2:178543276;178543275;178543274 | chr2:179408003;179408002;179408001 |
| N2AB | 30592 | 91999;92000;92001 | chr2:178543276;178543275;178543274 | chr2:179408003;179408002;179408001 |
| N2A | 29665 | 89218;89219;89220 | chr2:178543276;178543275;178543274 | chr2:179408003;179408002;179408001 |
| N2B | 23168 | 69727;69728;69729 | chr2:178543276;178543275;178543274 | chr2:179408003;179408002;179408001 |
| Novex-1 | 23293 | 70102;70103;70104 | chr2:178543276;178543275;178543274 | chr2:179408003;179408002;179408001 |
| Novex-2 | 23360 | 70303;70304;70305 | chr2:178543276;178543275;178543274 | chr2:179408003;179408002;179408001 |
| 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 | rs755082341  |
0.157 | 1.0 | N | 0.718 | 0.326 | 0.256283259241 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 9.94E-05 | 5.57E-05 | None | 0 | None | 0 | 2.67E-05 | 0 |
| R/Q | rs755082341 |
0.157 | 1.0 | N | 0.718 | 0.326 | 0.256283259241 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs755082341 |
0.157 | 1.0 | N | 0.718 | 0.326 | 0.256283259241 | gnomAD-4.0.0 | 1.42524E-05 | None | None | None | None | I | None | 0 | 1.66667E-05 | None | 3.37792E-05 | 2.22926E-05 | None | 0 | 0 | 1.44095E-05 | 2.19631E-05 | 1.60056E-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 | 0.6743 | likely_pathogenic | 0.5492 | ambiguous | -0.016 | Destabilizing | 0.998 | D | 0.595 | neutral | None | None | None | None | I |
| R/C | 0.3016 | likely_benign | 0.2359 | benign | -0.29 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | I |
| R/D | 0.9013 | likely_pathogenic | 0.843 | pathogenic | -0.317 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | I |
| R/E | 0.6874 | likely_pathogenic | 0.5992 | pathogenic | -0.287 | Destabilizing | 0.994 | D | 0.63 | neutral | None | None | None | None | I |
| R/F | 0.7482 | likely_pathogenic | 0.6529 | pathogenic | -0.357 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | I |
| R/G | 0.5693 | likely_pathogenic | 0.4417 | ambiguous | -0.135 | Destabilizing | 1.0 | D | 0.605 | neutral | N | 0.468167412 | None | None | I |
| R/H | 0.1603 | likely_benign | 0.1299 | benign | -0.582 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | I |
| R/I | 0.4808 | ambiguous | 0.3867 | ambiguous | 0.25 | Stabilizing | 0.999 | D | 0.662 | neutral | None | None | None | None | I |
| R/K | 0.1595 | likely_benign | 0.1254 | benign | -0.211 | Destabilizing | 0.964 | D | 0.486 | neutral | None | None | None | None | I |
| R/L | 0.4228 | ambiguous | 0.334 | benign | 0.25 | Stabilizing | 0.999 | D | 0.605 | neutral | N | 0.470368053 | None | None | I |
| R/M | 0.5443 | ambiguous | 0.4427 | ambiguous | -0.127 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| R/N | 0.8465 | likely_pathogenic | 0.7692 | pathogenic | -0.115 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | I |
| R/P | 0.5649 | likely_pathogenic | 0.4441 | ambiguous | 0.178 | Stabilizing | 1.0 | D | 0.668 | neutral | N | 0.396013738 | None | None | I |
| R/Q | 0.1925 | likely_benign | 0.1542 | benign | -0.159 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | N | 0.490542839 | None | None | I |
| R/S | 0.7875 | likely_pathogenic | 0.6884 | pathogenic | -0.293 | Destabilizing | 0.999 | D | 0.638 | neutral | None | None | None | None | I |
| R/T | 0.602 | likely_pathogenic | 0.4876 | ambiguous | -0.168 | Destabilizing | 0.999 | D | 0.631 | neutral | None | None | None | None | I |
| R/V | 0.5616 | ambiguous | 0.4579 | ambiguous | 0.178 | Stabilizing | 0.998 | D | 0.659 | neutral | None | None | None | None | I |
| R/W | 0.2888 | likely_benign | 0.2356 | benign | -0.547 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| R/Y | 0.5681 | likely_pathogenic | 0.4764 | ambiguous | -0.153 | Destabilizing | 0.999 | D | 0.673 | 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.