Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2622 | 8089;8090;8091 | chr2:178771463;178771462;178771461 | chr2:179636190;179636189;179636188 |
| N2AB | 2622 | 8089;8090;8091 | chr2:178771463;178771462;178771461 | chr2:179636190;179636189;179636188 |
| N2A | 2622 | 8089;8090;8091 | chr2:178771463;178771462;178771461 | chr2:179636190;179636189;179636188 |
| N2B | 2576 | 7951;7952;7953 | chr2:178771463;178771462;178771461 | chr2:179636190;179636189;179636188 |
| Novex-1 | 2576 | 7951;7952;7953 | chr2:178771463;178771462;178771461 | chr2:179636190;179636189;179636188 |
| Novex-2 | 2576 | 7951;7952;7953 | chr2:178771463;178771462;178771461 | chr2:179636190;179636189;179636188 |
| Novex-3 | 2622 | 8089;8090;8091 | chr2:178771463;178771462;178771461 | chr2:179636190;179636189;179636188 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs148394362  |
-1.257 | 0.993 | D | 0.456 | 0.46 | None | gnomAD-2.1.1 | 1.06E-05 | None | None | None | None | N | None | 4E-05 | 0 | None | 0 | 5.02E-05 | None | 0 | None | 0 | 7.76E-06 | 0 |
| I/V | rs148394362 |
-1.257 | 0.993 | D | 0.456 | 0.46 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 1.9253E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs148394362 |
-1.257 | 0.993 | D | 0.456 | 0.46 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| I/V | rs148394362 |
-1.257 | 0.993 | D | 0.456 | 0.46 | None | gnomAD-4.0.0 | 7.68443E-06 | None | None | None | None | N | None | 5.06141E-05 | 0 | None | 0 | 4.85084E-05 | None | 0 | 0 | 2.39283E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9497 | likely_pathogenic | 0.9565 | pathogenic | -1.748 | Destabilizing | 0.999 | D | 0.652 | neutral | None | None | None | None | N |
| I/C | 0.9855 | likely_pathogenic | 0.987 | pathogenic | -1.15 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| I/D | 0.9964 | likely_pathogenic | 0.9965 | pathogenic | -1.359 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| I/E | 0.9907 | likely_pathogenic | 0.9911 | pathogenic | -1.361 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| I/F | 0.5416 | ambiguous | 0.5515 | ambiguous | -1.325 | Destabilizing | 1.0 | D | 0.793 | deleterious | N | 0.477502939 | None | None | N |
| I/G | 0.9937 | likely_pathogenic | 0.9949 | pathogenic | -2.071 | Highly Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| I/H | 0.9887 | likely_pathogenic | 0.9886 | pathogenic | -1.332 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| I/K | 0.9776 | likely_pathogenic | 0.9763 | pathogenic | -1.173 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| I/L | 0.3662 | ambiguous | 0.3929 | ambiguous | -0.931 | Destabilizing | 0.993 | D | 0.511 | neutral | D | 0.550223337 | None | None | N |
| I/M | 0.4598 | ambiguous | 0.4813 | ambiguous | -0.734 | Destabilizing | 1.0 | D | 0.765 | deleterious | D | 0.668132939 | None | None | N |
| I/N | 0.9602 | likely_pathogenic | 0.9639 | pathogenic | -1.0 | Destabilizing | 1.0 | D | 0.836 | deleterious | D | 0.709514006 | None | None | N |
| I/P | 0.9859 | likely_pathogenic | 0.9857 | pathogenic | -1.173 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| I/Q | 0.9843 | likely_pathogenic | 0.9839 | pathogenic | -1.211 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| I/R | 0.9669 | likely_pathogenic | 0.9655 | pathogenic | -0.577 | Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| I/S | 0.962 | likely_pathogenic | 0.9669 | pathogenic | -1.605 | Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.708705487 | None | None | N |
| I/T | 0.9383 | likely_pathogenic | 0.9495 | pathogenic | -1.492 | Destabilizing | 1.0 | D | 0.802 | deleterious | D | 0.708249937 | None | None | N |
| I/V | 0.1357 | likely_benign | 0.147 | benign | -1.173 | Destabilizing | 0.993 | D | 0.456 | neutral | D | 0.562300172 | None | None | N |
| I/W | 0.9884 | likely_pathogenic | 0.9878 | pathogenic | -1.392 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| I/Y | 0.9499 | likely_pathogenic | 0.9524 | pathogenic | -1.159 | Destabilizing | 1.0 | D | 0.786 | deleterious | 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.