Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2654 | 8185;8186;8187 | chr2:178771367;178771366;178771365 | chr2:179636094;179636093;179636092 |
| N2AB | 2654 | 8185;8186;8187 | chr2:178771367;178771366;178771365 | chr2:179636094;179636093;179636092 |
| N2A | 2654 | 8185;8186;8187 | chr2:178771367;178771366;178771365 | chr2:179636094;179636093;179636092 |
| N2B | 2608 | 8047;8048;8049 | chr2:178771367;178771366;178771365 | chr2:179636094;179636093;179636092 |
| Novex-1 | 2608 | 8047;8048;8049 | chr2:178771367;178771366;178771365 | chr2:179636094;179636093;179636092 |
| Novex-2 | 2608 | 8047;8048;8049 | chr2:178771367;178771366;178771365 | chr2:179636094;179636093;179636092 |
| Novex-3 | 2654 | 8185;8186;8187 | chr2:178771367;178771366;178771365 | chr2:179636094;179636093;179636092 |
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/K | rs147207100  |
-1.505 | None | N | 0.137 | 0.104 | None | gnomAD-2.1.1 | 2.75942E-04 | None | None | None | None | N | None | 3.04414E-03 | 2.82E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/K | rs147207100 |
-1.505 | None | N | 0.137 | 0.104 | None | gnomAD-3.1.2 | 8.74425E-04 | None | None | None | None | N | None | 3.0666E-03 | 3.27439E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.77555E-04 |
| R/K | rs147207100 |
-1.505 | None | N | 0.137 | 0.104 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/K | rs147207100 |
-1.505 | None | N | 0.137 | 0.104 | None | gnomAD-4.0.0 | 1.88972E-04 | None | None | None | None | N | None | 3.74587E-03 | 1.66656E-04 | None | 0 | 0 | None | 0 | 1.64962E-04 | 8.47479E-07 | 0 | 1.91975E-04 |
| R/S | rs1422023102 |
None | 0.012 | N | 0.499 | 0.073 | 0.143124449307 | gnomAD-4.0.0 | 6.84097E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99316E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4279 | ambiguous | 0.4388 | ambiguous | -1.379 | Destabilizing | 0.016 | N | 0.424 | neutral | None | None | None | None | N |
| R/C | 0.19 | likely_benign | 0.2133 | benign | -1.262 | Destabilizing | 0.864 | D | 0.659 | neutral | None | None | None | None | N |
| R/D | 0.8578 | likely_pathogenic | 0.8625 | pathogenic | -0.263 | Destabilizing | 0.072 | N | 0.562 | neutral | None | None | None | None | N |
| R/E | 0.4198 | ambiguous | 0.4128 | ambiguous | -0.108 | Destabilizing | 0.007 | N | 0.345 | neutral | None | None | None | None | N |
| R/F | 0.5459 | ambiguous | 0.5411 | ambiguous | -1.158 | Destabilizing | 0.628 | D | 0.657 | neutral | None | None | None | None | N |
| R/G | 0.439 | ambiguous | 0.4481 | ambiguous | -1.713 | Destabilizing | 0.024 | N | 0.53 | neutral | N | 0.41367692 | None | None | N |
| R/H | 0.1555 | likely_benign | 0.1589 | benign | -1.955 | Destabilizing | 0.356 | N | 0.578 | neutral | None | None | None | None | N |
| R/I | 0.1923 | likely_benign | 0.196 | benign | -0.457 | Destabilizing | 0.356 | N | 0.678 | prob.neutral | None | None | None | None | N |
| R/K | 0.0605 | likely_benign | 0.0626 | benign | -1.109 | Destabilizing | None | N | 0.137 | neutral | N | 0.292127883 | None | None | N |
| R/L | 0.2193 | likely_benign | 0.2188 | benign | -0.457 | Destabilizing | 0.031 | N | 0.53 | neutral | None | None | None | None | N |
| R/M | 0.2052 | likely_benign | 0.212 | benign | -0.713 | Destabilizing | 0.56 | D | 0.623 | neutral | N | 0.413255838 | None | None | N |
| R/N | 0.6688 | likely_pathogenic | 0.694 | pathogenic | -0.677 | Destabilizing | 0.072 | N | 0.527 | neutral | None | None | None | None | N |
| R/P | 0.9438 | likely_pathogenic | 0.9277 | pathogenic | -0.746 | Destabilizing | 0.136 | N | 0.619 | neutral | None | None | None | None | N |
| R/Q | 0.1186 | likely_benign | 0.121 | benign | -0.812 | Destabilizing | 0.001 | N | 0.177 | neutral | None | None | None | None | N |
| R/S | 0.5847 | likely_pathogenic | 0.6089 | pathogenic | -1.617 | Destabilizing | 0.012 | N | 0.499 | neutral | N | 0.343402945 | None | None | N |
| R/T | 0.3475 | ambiguous | 0.3516 | ambiguous | -1.254 | Destabilizing | 0.055 | N | 0.591 | neutral | N | 0.357020796 | None | None | N |
| R/V | 0.2911 | likely_benign | 0.2982 | benign | -0.746 | Destabilizing | 0.072 | N | 0.603 | neutral | None | None | None | None | N |
| R/W | 0.2639 | likely_benign | 0.2394 | benign | -0.71 | Destabilizing | 0.828 | D | 0.675 | prob.neutral | N | 0.377713459 | None | None | N |
| R/Y | 0.4351 | ambiguous | 0.4423 | ambiguous | -0.461 | Destabilizing | 0.356 | N | 0.654 | neutral | 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.