Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19240 | 57943;57944;57945 | chr2:178595636;178595635;178595634 | chr2:179460363;179460362;179460361 |
| N2AB | 17599 | 53020;53021;53022 | chr2:178595636;178595635;178595634 | chr2:179460363;179460362;179460361 |
| N2A | 16672 | 50239;50240;50241 | chr2:178595636;178595635;178595634 | chr2:179460363;179460362;179460361 |
| N2B | 10175 | 30748;30749;30750 | chr2:178595636;178595635;178595634 | chr2:179460363;179460362;179460361 |
| Novex-1 | 10300 | 31123;31124;31125 | chr2:178595636;178595635;178595634 | chr2:179460363;179460362;179460361 |
| Novex-2 | 10367 | 31324;31325;31326 | chr2:178595636;178595635;178595634 | chr2:179460363;179460362;179460361 |
| 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 | rs535940583  |
0.108 | 1.0 | N | 0.699 | 0.35 | 0.21279746466 | gnomAD-2.1.1 | 4.25E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.51247E-04 | None | 0 | 0 | 0 |
| R/Q | rs535940583 |
0.108 | 1.0 | N | 0.699 | 0.35 | 0.21279746466 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 4.15282E-04 | 0 |
| R/Q | rs535940583 |
0.108 | 1.0 | N | 0.699 | 0.35 | 0.21279746466 | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 2E-03 | None |
| R/Q | rs535940583 |
0.108 | 1.0 | N | 0.699 | 0.35 | 0.21279746466 | gnomAD-4.0.0 | 2.49257E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.02092E-05 | 2.91565E-04 | 3.21585E-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 | 0.7771 | likely_pathogenic | 0.7829 | pathogenic | 0.068 | Stabilizing | 0.999 | D | 0.626 | neutral | None | None | None | None | I |
| R/C | 0.43 | ambiguous | 0.4594 | ambiguous | -0.132 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | I |
| R/D | 0.9015 | likely_pathogenic | 0.9141 | pathogenic | -0.125 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | I |
| R/E | 0.7112 | likely_pathogenic | 0.7285 | pathogenic | -0.055 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | I |
| R/F | 0.8645 | likely_pathogenic | 0.8832 | pathogenic | -0.119 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | I |
| R/G | 0.589 | likely_pathogenic | 0.6218 | pathogenic | -0.133 | Destabilizing | 1.0 | D | 0.623 | neutral | N | 0.484118299 | None | None | I |
| R/H | 0.2531 | likely_benign | 0.2743 | benign | -0.643 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | I |
| R/I | 0.7418 | likely_pathogenic | 0.749 | pathogenic | 0.561 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | I |
| R/K | 0.2424 | likely_benign | 0.2595 | benign | -0.05 | Destabilizing | 0.998 | D | 0.482 | neutral | None | None | None | None | I |
| R/L | 0.6157 | likely_pathogenic | 0.6148 | pathogenic | 0.561 | Stabilizing | 1.0 | D | 0.623 | neutral | D | 0.523116617 | None | None | I |
| R/M | 0.6971 | likely_pathogenic | 0.7188 | pathogenic | 0.053 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| R/N | 0.8531 | likely_pathogenic | 0.8717 | pathogenic | 0.119 | Stabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | I |
| R/P | 0.9302 | likely_pathogenic | 0.9359 | pathogenic | 0.417 | Stabilizing | 1.0 | D | 0.673 | neutral | N | 0.514497134 | None | None | I |
| R/Q | 0.2467 | likely_benign | 0.2458 | benign | 0.06 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.474554666 | None | None | I |
| R/S | 0.8054 | likely_pathogenic | 0.8215 | pathogenic | -0.17 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| R/T | 0.6973 | likely_pathogenic | 0.7076 | pathogenic | 0.035 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| R/V | 0.7686 | likely_pathogenic | 0.7738 | pathogenic | 0.417 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| R/W | 0.4172 | ambiguous | 0.4583 | ambiguous | -0.2 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| R/Y | 0.7022 | likely_pathogenic | 0.7478 | pathogenic | 0.209 | Stabilizing | 1.0 | D | 0.694 | prob.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.