Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27806 | 83641;83642;83643 | chr2:178562716;178562715;178562714 | chr2:179427443;179427442;179427441 |
| N2AB | 26165 | 78718;78719;78720 | chr2:178562716;178562715;178562714 | chr2:179427443;179427442;179427441 |
| N2A | 25238 | 75937;75938;75939 | chr2:178562716;178562715;178562714 | chr2:179427443;179427442;179427441 |
| N2B | 18741 | 56446;56447;56448 | chr2:178562716;178562715;178562714 | chr2:179427443;179427442;179427441 |
| Novex-1 | 18866 | 56821;56822;56823 | chr2:178562716;178562715;178562714 | chr2:179427443;179427442;179427441 |
| Novex-2 | 18933 | 57022;57023;57024 | chr2:178562716;178562715;178562714 | chr2:179427443;179427442;179427441 |
| 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 | rs192301247  |
-1.143 | 1.0 | N | 0.675 | 0.421 | None | gnomAD-2.1.1 | 1.27E-05 | None | None | None | None | N | None | 0 | 6.25E-05 | None | 0 | 0 | None | 0 | None | 0 | 9.17E-06 | 0 |
| R/Q | rs192301247 |
-1.143 | 1.0 | N | 0.675 | 0.421 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 1.92976E-04 | None | 0 | 0 | 4.41E-05 | 2.06954E-04 | 0 |
| R/Q | rs192301247 |
-1.143 | 1.0 | N | 0.675 | 0.421 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/Q | rs192301247 |
-1.143 | 1.0 | N | 0.675 | 0.421 | None | gnomAD-4.0.0 | 1.00189E-05 | None | None | None | None | N | None | 1.35186E-05 | 3.50373E-05 | None | 0 | 2.24004E-05 | None | 0 | 0 | 8.5275E-06 | 2.28133E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9837 | likely_pathogenic | 0.9906 | pathogenic | -2.121 | Highly Destabilizing | 1.0 | D | 0.535 | neutral | None | None | None | None | N |
| R/C | 0.7116 | likely_pathogenic | 0.8275 | pathogenic | -1.958 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| R/D | 0.9985 | likely_pathogenic | 0.9992 | pathogenic | -0.879 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| R/E | 0.9795 | likely_pathogenic | 0.9877 | pathogenic | -0.668 | Destabilizing | 1.0 | D | 0.529 | neutral | None | None | None | None | N |
| R/F | 0.9903 | likely_pathogenic | 0.9952 | pathogenic | -1.378 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| R/G | 0.9722 | likely_pathogenic | 0.9867 | pathogenic | -2.466 | Highly Destabilizing | 1.0 | D | 0.774 | deleterious | N | 0.500744121 | None | None | N |
| R/H | 0.685 | likely_pathogenic | 0.8079 | pathogenic | -2.232 | Highly Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| R/I | 0.9818 | likely_pathogenic | 0.9886 | pathogenic | -1.122 | Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| R/K | 0.3647 | ambiguous | 0.4711 | ambiguous | -1.418 | Destabilizing | 0.998 | D | 0.464 | neutral | None | None | None | None | N |
| R/L | 0.9429 | likely_pathogenic | 0.9657 | pathogenic | -1.122 | Destabilizing | 1.0 | D | 0.774 | deleterious | N | 0.507389938 | None | None | N |
| R/M | 0.9478 | likely_pathogenic | 0.9738 | pathogenic | -1.542 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| R/N | 0.9942 | likely_pathogenic | 0.9969 | pathogenic | -1.301 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/P | 0.9994 | likely_pathogenic | 0.9996 | pathogenic | -1.444 | Destabilizing | 1.0 | D | 0.881 | deleterious | D | 0.544447822 | None | None | N |
| R/Q | 0.5384 | ambiguous | 0.6963 | pathogenic | -1.243 | Destabilizing | 1.0 | D | 0.675 | neutral | N | 0.485193852 | None | None | N |
| R/S | 0.9942 | likely_pathogenic | 0.9973 | pathogenic | -2.287 | Highly Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| R/T | 0.988 | likely_pathogenic | 0.9947 | pathogenic | -1.862 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| R/V | 0.9813 | likely_pathogenic | 0.9879 | pathogenic | -1.444 | Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| R/W | 0.8812 | likely_pathogenic | 0.9449 | pathogenic | -0.821 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| R/Y | 0.9531 | likely_pathogenic | 0.9778 | pathogenic | -0.703 | Destabilizing | 1.0 | D | 0.905 | 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.