Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2014 | 6265;6266;6267 | chr2:178775824;178775823;178775822 | chr2:179640551;179640550;179640549 |
| N2AB | 2014 | 6265;6266;6267 | chr2:178775824;178775823;178775822 | chr2:179640551;179640550;179640549 |
| N2A | 2014 | 6265;6266;6267 | chr2:178775824;178775823;178775822 | chr2:179640551;179640550;179640549 |
| N2B | 1968 | 6127;6128;6129 | chr2:178775824;178775823;178775822 | chr2:179640551;179640550;179640549 |
| Novex-1 | 1968 | 6127;6128;6129 | chr2:178775824;178775823;178775822 | chr2:179640551;179640550;179640549 |
| Novex-2 | 1968 | 6127;6128;6129 | chr2:178775824;178775823;178775822 | chr2:179640551;179640550;179640549 |
| Novex-3 | 2014 | 6265;6266;6267 | chr2:178775824;178775823;178775822 | chr2:179640551;179640550;179640549 |
Information
- RefSeq wild type amino acid: T
- RefSeq wild type transcript codon: ACC
- RefSeq wild type template codon: TGG
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs180672509  |
None | None | N | None | 0.153 | None | gnomAD-2.1.1 | 1.45209E-04 | None | None | None | None | None | 0 | 0 | None | 0 | 2.05493E-03 | None | 0 | None | 0 | 0 | 0 | |
| T/A | rs180672509 |
None | None | N | None | 0.153 | None | gnomAD-3.1.2 | 5.91E-05 | None | None | None | None | None | 0 | 0 | 0 | 0 | 1.7321E-03 | None | 0 | 0 | 0 | 0 | 0 | |
| T/A | rs180672509 |
None | None | N | None | 0.153 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | None | 0 | 0 | None | None | 3E-03 | 0 | None | None | None | 0 | None | |
| T/A | rs180672509 |
None | None | N | None | 0.153 | None |
Huang (2021)
| None |
Other 
|
comp het with R33903H (in cis), c.1800+1G>A (in trans) | None | None | Genetic analysis of NMD patients; variant prioritisation; no validation | None | None | None | None | None | None | None | None | None | None | None | |
| T/A | rs180672509 |
None | None | N | None | 0.153 | None | gnomAD-4.0.0 | 3.03591E-05 | None | None | None | None | None | 0 | 0 | None | 0 | 1.06947E-03 | None | 0 | 0 | 0 | 0 | 1.60005E-05 | |
| T/I | rs189149543 |
None | None | N | None | 0.549 | None | gnomAD-2.1.1 | 1.01306E-03 | None | None | None | None | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 9.44449E-03 | 2.64041E-04 | 2.08333E-03 | |
| T/I | rs189149543 |
None | None | N | None | 0.549 | None | gnomAD-3.1.2 | 6.3752E-04 | None | None | None | None | None | 0 | 0 | 0 | 0 | 0 | None | 7.63575E-03 | 0 | 2.20491E-04 | 0 | 4.78011E-04 | |
| T/I | rs189149543 |
None | None | N | None | 0.549 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | None | 0 | 0 | None | None | 0 | 2E-03 | None | None | None | 0 | None | |
| T/I | rs189149543 |
None | None | N | None | 0.549 | None | gnomAD-4.0.0 | 4.29386E-04 | None | None | None | None | None | 0 | 0 | None | 0 | 0 | None | 9.42305E-03 | 0 | 4.83068E-05 | 0 | 5.28034E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.3229 | likely_benign | 0.3752 | ambiguous | None | None | None | None | None | None | N | 0.471325082 | None | None | |
| T/C | 0.9196 | likely_pathogenic | 0.8415 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| T/D | 0.8441 | likely_pathogenic | 0.8418 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| T/E | 0.7775 | likely_pathogenic | 0.7107 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| T/F | 0.8717 | likely_pathogenic | 0.8229 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| T/G | 0.6383 | likely_pathogenic | 0.6237 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| T/H | 0.7501 | likely_pathogenic | 0.6814 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| T/I | 0.847 | likely_pathogenic | 0.8964 | pathogenic | None | None | None | None | None | None | N | 0.488061923 | None | None | |
| T/K | 0.6907 | likely_pathogenic | 0.5979 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| T/L | 0.4993 | ambiguous | 0.4028 | ambiguous | None | None | None | None | None | None | None | None | None | None | |
| T/M | 0.38 | ambiguous | 0.2759 | benign | None | None | None | None | None | None | None | None | None | None | |
| T/N | 0.5174 | ambiguous | 0.4946 | ambiguous | None | None | None | None | None | None | N | 0.4879179 | None | None | |
| T/P | 0.5407 | ambiguous | 0.6565 | pathogenic | None | None | None | None | None | None | N | 0.488594638 | None | None | |
| T/Q | 0.6667 | likely_pathogenic | 0.5762 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| T/R | 0.6302 | likely_pathogenic | 0.5054 | ambiguous | None | None | None | None | None | None | None | None | None | None | |
| T/S | 0.2938 | likely_benign | 0.2808 | benign | None | None | None | None | None | None | N | 0.45920018 | None | None | |
| T/V | 0.6754 | likely_pathogenic | 0.5663 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| T/W | 0.9513 | likely_pathogenic | 0.9272 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| T/Y | 0.8726 | likely_pathogenic | 0.8255 | pathogenic | None | None | None | None | None | None | None | None | None | None |
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.