Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7321 | 22186;22187;22188 | chr2:178723046;178722937;178722936 | chr2:179587773;179587664;179587663 |
| N2AB | 7004 | 21235;21236;21237 | chr2:178723046;178722937;178722936 | chr2:179587773;179587664;179587663 |
| N2A | 6077 | 18454;18455;18456 | chr2:178723046;178722937;178722936 | chr2:179587773;179587664;179587663 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
- RefSeq wild type amino acid: E
- RefSeq wild type transcript codon: GAA
- RefSeq wild type template codon: CTT
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/K | rs2078691261  |
None | None | N | None | 0.245 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 | |
| E/K | rs2078691261 |
None | None | N | None | 0.245 | None |
Ceyhan-Birsoy (2013)
| None |
CNM 
|
comp het with K16972fs | None | None | WES/WGS prioritisation; increased titin degradation/truncation in patient muscles; comp het with K16972fs (N2A) | None | None | None | None | None | None | None | None | None | None | None | |
| E/K | rs2078691261 |
None | None | N | None | 0.245 | None | gnomAD-4.0.0 | 6.19962E-06 | None | None | None | None | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47844E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.3588 | ambiguous | 0.4439 | ambiguous | None | None | None | None | None | None | N | 0.454401894 | None | None | |
| E/C | 0.9409 | likely_pathogenic | 0.9622 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| E/D | 0.4142 | ambiguous | 0.5275 | ambiguous | None | None | None | None | None | None | N | 0.46026079 | None | None | |
| E/F | 0.8921 | likely_pathogenic | 0.9287 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| E/G | 0.4866 | ambiguous | 0.5963 | pathogenic | None | None | None | None | None | None | N | 0.465567162 | None | None | |
| E/H | 0.7618 | likely_pathogenic | 0.8169 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| E/I | 0.5238 | ambiguous | 0.6129 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| E/K | 0.4389 | ambiguous | 0.4174 | ambiguous | None | None | None | None | None | None | N | 0.482091709 | None | None | |
| E/L | 0.5734 | likely_pathogenic | 0.6774 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| E/M | 0.6508 | likely_pathogenic | 0.7382 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| E/N | 0.6379 | likely_pathogenic | 0.7318 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| E/P | 0.9425 | likely_pathogenic | 0.9604 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| E/Q | 0.2205 | likely_benign | 0.2632 | benign | None | None | None | None | None | None | N | 0.486473029 | None | None | |
| E/R | 0.5765 | likely_pathogenic | 0.6498 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| E/S | 0.4503 | ambiguous | 0.5472 | ambiguous | None | None | None | None | None | None | None | None | None | None | |
| E/T | 0.493 | ambiguous | 0.5756 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| E/V | 0.3224 | likely_benign | 0.3925 | ambiguous | None | None | None | None | None | None | N | 0.509042881 | None | None | |
| E/W | 0.9712 | likely_pathogenic | 0.9831 | pathogenic | None | None | None | None | None | None | None | None | None | None | |
| E/Y | 0.8296 | likely_pathogenic | 0.8815 | 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.