Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26331 | 79216;79217;79218 | chr2:178567141;178567140;178567139 | chr2:179431868;179431867;179431866 |
| N2AB | 24690 | 74293;74294;74295 | chr2:178567141;178567140;178567139 | chr2:179431868;179431867;179431866 |
| N2A | 23763 | 71512;71513;71514 | chr2:178567141;178567140;178567139 | chr2:179431868;179431867;179431866 |
| N2B | 17266 | 52021;52022;52023 | chr2:178567141;178567140;178567139 | chr2:179431868;179431867;179431866 |
| Novex-1 | 17391 | 52396;52397;52398 | chr2:178567141;178567140;178567139 | chr2:179431868;179431867;179431866 |
| Novex-2 | 17458 | 52597;52598;52599 | chr2:178567141;178567140;178567139 | chr2:179431868;179431867;179431866 |
| 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 | rs758190406  |
-0.025 | 1.0 | N | 0.597 | 0.408 | 0.221019684889 | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | I | None | 2.06731E-04 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 7.85E-06 | 0 |
| R/Q | rs758190406 |
-0.025 | 1.0 | N | 0.597 | 0.408 | 0.221019684889 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/Q | rs758190406 |
-0.025 | 1.0 | N | 0.597 | 0.408 | 0.221019684889 | gnomAD-4.0.0 | 1.61154E-05 | None | None | None | None | I | None | 9.34879E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47745E-06 | 6.58892E-05 | 4.80461E-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 | 0.9916 | likely_pathogenic | 0.993 | pathogenic | -0.274 | Destabilizing | 0.999 | D | 0.461 | neutral | None | None | None | None | I |
| R/C | 0.8561 | likely_pathogenic | 0.9031 | pathogenic | -0.369 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| R/D | 0.9974 | likely_pathogenic | 0.998 | pathogenic | -0.029 | Destabilizing | 1.0 | D | 0.602 | neutral | None | None | None | None | I |
| R/E | 0.9861 | likely_pathogenic | 0.9899 | pathogenic | 0.039 | Stabilizing | 0.999 | D | 0.503 | neutral | None | None | None | None | I |
| R/F | 0.9872 | likely_pathogenic | 0.9913 | pathogenic | -0.455 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| R/G | 0.9823 | likely_pathogenic | 0.9849 | pathogenic | -0.484 | Destabilizing | 1.0 | D | 0.512 | neutral | N | 0.519689523 | None | None | I |
| R/H | 0.5006 | ambiguous | 0.5909 | pathogenic | -0.869 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| R/I | 0.9852 | likely_pathogenic | 0.9912 | pathogenic | 0.25 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| R/K | 0.7823 | likely_pathogenic | 0.8066 | pathogenic | -0.312 | Destabilizing | 0.998 | D | 0.408 | neutral | None | None | None | None | I |
| R/L | 0.9493 | likely_pathogenic | 0.9692 | pathogenic | 0.25 | Stabilizing | 1.0 | D | 0.512 | neutral | N | 0.493903585 | None | None | I |
| R/M | 0.9855 | likely_pathogenic | 0.9916 | pathogenic | -0.087 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| R/N | 0.9906 | likely_pathogenic | 0.9925 | pathogenic | 0.02 | Stabilizing | 1.0 | D | 0.609 | neutral | None | None | None | None | I |
| R/P | 0.9971 | likely_pathogenic | 0.9976 | pathogenic | 0.095 | Stabilizing | 1.0 | D | 0.615 | neutral | N | 0.483054258 | None | None | I |
| R/Q | 0.7854 | likely_pathogenic | 0.8051 | pathogenic | -0.141 | Destabilizing | 1.0 | D | 0.597 | neutral | N | 0.477102776 | None | None | I |
| R/S | 0.9907 | likely_pathogenic | 0.9923 | pathogenic | -0.485 | Destabilizing | 1.0 | D | 0.572 | neutral | None | None | None | None | I |
| R/T | 0.9905 | likely_pathogenic | 0.9933 | pathogenic | -0.276 | Destabilizing | 1.0 | D | 0.569 | neutral | None | None | None | None | I |
| R/V | 0.986 | likely_pathogenic | 0.9917 | pathogenic | 0.095 | Stabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | I |
| R/W | 0.8612 | likely_pathogenic | 0.9103 | pathogenic | -0.395 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | I |
| R/Y | 0.9609 | likely_pathogenic | 0.9704 | pathogenic | -0.015 | Destabilizing | 1.0 | D | 0.667 | 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.