Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31791 | 95596;95597;95598 | chr2:178545865;178545864;178545863 | chr2:179410592;179410591;179410590 |
| N2AB | 30150 | 90673;90674;90675 | chr2:178545865;178545864;178545863 | chr2:179410592;179410591;179410590 |
| N2A | 29223 | 87892;87893;87894 | chr2:178545865;178545864;178545863 | chr2:179410592;179410591;179410590 |
| N2B | 22726 | 68401;68402;68403 | chr2:178545865;178545864;178545863 | chr2:179410592;179410591;179410590 |
| Novex-1 | 22851 | 68776;68777;68778 | chr2:178545865;178545864;178545863 | chr2:179410592;179410591;179410590 |
| Novex-2 | 22918 | 68977;68978;68979 | chr2:178545865;178545864;178545863 | chr2:179410592;179410591;179410590 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/D | rs869320744  |
-1.821 | 1.0 | D | 0.875 | 0.944 | 0.495038369364 |
Toro (2013)
Uruha (2015)
| None |
MFM 
HMERF
|
het | None | None | N | WES prioritisation of single US family + 45 unrelated probands; Genetic analysis of Fn3-119 in 187 MFM patients to assess diagnostic value of sub-sarcolemmal necklace alignments of cytoplasmic bodies for HMERF | None | None | None | None | None | None | None | None | None | None | None |
| G/R | rs1696856005 |
-1.008 | 1.0 | D | 0.916 | 0.954 | 0.703283205912 |
Uruha (2015)
| None |
MFM
HMERF
|
het | None | None | N | Genetic analysis of Fn3-119 in 187 MFM patients to assess diagnostic value of sub-sarcolemmal necklace alignments of cytoplasmic bodies for HMERF | None | None | None | None | None | None | None | None | None | None | None |
| G/V | None | -0.713 | 1.0 | D | 0.903 | 0.916 | 0.684650895497 |
Uruha (2015)
| None |
MFM
HMERF
|
het | None | None | N | Genetic analysis of Fn3-119 in 187 MFM patients to assess diagnostic value of sub-sarcolemmal necklace alignments of cytoplasmic bodies for HMERF | None | None | None | None | None | None | None | None | None | None | None |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.5817 | likely_pathogenic | 0.5984 | pathogenic | -0.911 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | D | 0.550722608 | None | None | N |
| G/C | 0.9135 | likely_pathogenic | 0.9239 | pathogenic | -1.167 | Destabilizing | 1.0 | D | 0.865 | deleterious | D | 0.56385334 | None | None | N |
| G/D | 0.984 | likely_pathogenic | 0.9869 | pathogenic | -1.545 | Destabilizing | 1.0 | D | 0.875 | deleterious | D | 0.562839382 | None | None | N |
| G/E | 0.9905 | likely_pathogenic | 0.9919 | pathogenic | -1.628 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| G/F | 0.9963 | likely_pathogenic | 0.9969 | pathogenic | -1.276 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| G/H | 0.9937 | likely_pathogenic | 0.994 | pathogenic | -1.302 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| G/I | 0.9935 | likely_pathogenic | 0.9948 | pathogenic | -0.648 | Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| G/K | 0.9977 | likely_pathogenic | 0.9979 | pathogenic | -1.368 | Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | N |
| G/L | 0.9907 | likely_pathogenic | 0.9911 | pathogenic | -0.648 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| G/M | 0.9917 | likely_pathogenic | 0.9925 | pathogenic | -0.578 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| G/N | 0.9828 | likely_pathogenic | 0.9848 | pathogenic | -1.069 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| G/P | 0.9988 | likely_pathogenic | 0.9988 | pathogenic | -0.698 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| G/Q | 0.991 | likely_pathogenic | 0.9918 | pathogenic | -1.342 | Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| G/R | 0.9924 | likely_pathogenic | 0.9928 | pathogenic | -0.934 | Destabilizing | 1.0 | D | 0.916 | deleterious | D | 0.563092872 | None | None | N |
| G/S | 0.3242 | likely_benign | 0.3467 | ambiguous | -1.28 | Destabilizing | 1.0 | D | 0.819 | deleterious | N | 0.490759057 | None | None | N |
| G/T | 0.8961 | likely_pathogenic | 0.9078 | pathogenic | -1.299 | Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| G/V | 0.9787 | likely_pathogenic | 0.9832 | pathogenic | -0.698 | Destabilizing | 1.0 | D | 0.903 | deleterious | D | 0.563346361 | None | None | N |
| G/W | 0.9935 | likely_pathogenic | 0.9944 | pathogenic | -1.518 | Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| G/Y | 0.9948 | likely_pathogenic | 0.9956 | pathogenic | -1.166 | Destabilizing | 1.0 | D | 0.879 | 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.