Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34091 | 102496;102497;102498 | chr2:178534344;178534343;178534342 | chr2:179399071;179399070;179399069 |
| N2AB | 32450 | 97573;97574;97575 | chr2:178534344;178534343;178534342 | chr2:179399071;179399070;179399069 |
| N2A | 31523 | 94792;94793;94794 | chr2:178534344;178534343;178534342 | chr2:179399071;179399070;179399069 |
| N2B | 25026 | 75301;75302;75303 | chr2:178534344;178534343;178534342 | chr2:179399071;179399070;179399069 |
| Novex-1 | 25151 | 75676;75677;75678 | chr2:178534344;178534343;178534342 | chr2:179399071;179399070;179399069 |
| Novex-2 | 25218 | 75877;75878;75879 | chr2:178534344;178534343;178534342 | chr2:179399071;179399070;179399069 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
- RefSeq wild type amino acid: R
- RefSeq wild type transcript codon: CGG
- RefSeq wild type template codon: GCC
- Domain: Kinase-1
- Domain position: 279
- Q(SASA): 0.3625
- Predicted PPI site: N
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 | rs763708375  |
-0.193 | None | N | None | 0.195 | 0.146414634003 | gnomAD-2.1.1 | 3.23E-05 | None | None | None | None | N | None | 8.27E-05 | 8.49E-05 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 1.57E-05 | 0 |
| R/Q | rs763708375 |
-0.193 | None | N | None | 0.195 | 0.146414634003 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 2.07039E-04 | 0 |
| R/Q | rs763708375 |
-0.193 | None | N | None | 0.195 | 0.146414634003 | gnomAD-4.0.0 | 7.07026E-05 | None | None | None | None | N | None | 6.67735E-05 | 8.335E-05 | None | 0 | 2.22787E-05 | None | 0 | 0 | 8.56058E-05 | 1.09784E-05 | 1.60113E-05 |
| R/W | rs140319117 |
-0.302 | None | N | None | 0.328 | None | gnomAD-2.1.1 | 1.01552E-03 | None | None | None | None | N | None | 3.30852E-04 | 1.35793E-03 | None | 3.00097E-03 | 0 | None | 6.54E-05 | None | 4.19E-05 | 1.43289E-03 | 1.40687E-03 |
| R/W | rs140319117 |
-0.302 | None | N | None | 0.328 | None | gnomAD-3.1.2 | 9.7976E-04 | None | None | None | None | N | None | 2.41476E-04 | 1.2459E-03 | 0 | 2.59665E-03 | 0 | None | 9.44E-05 | 0 | 1.52896E-03 | 4.1425E-04 | 1.91205E-03 |
| R/W | rs140319117 |
-0.302 | None | N | None | 0.328 | None | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 3E-03 | None | None | None | 0 | None |
| R/W | rs140319117 |
-0.302 | None | N | None | 0.328 | None |
Lange (2005)
Lange (2014)
| None |
HMERF
|
comp het with P31732L | None | None | N | WGS prioritisation in 2 Swedish families; greatly reduces interaction of kinase with nbr1; nbr1 and MuRF1 show diffuse localisation; comp het with Fn3-119 variants, re-classified as benign; subsequent argument it may be modulatory to incompletely penetrant P31732L variant | None | None | None | None | None | None | None | None | None | None | None |
| R/W | rs140319117 |
-0.302 | None | N | None | 0.328 | None | gnomAD-4.0.0 | 1.37625E-03 | None | None | None | None | N | None | 2.66667E-04 | 1.35018E-03 | None | 2.83784E-03 | 2.22856E-05 | None | 4.7957E-05 | 1.48466E-03 | 1.62993E-03 | 1.31749E-04 | 1.37657E-03 |
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 | 0.8825 | likely_pathogenic | 0.907 | pathogenic | -1.081 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/C | 0.6514 | likely_pathogenic | 0.7263 | pathogenic | -0.863 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/D | 0.9656 | likely_pathogenic | 0.9657 | pathogenic | -0.251 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/E | 0.8031 | likely_pathogenic | 0.8233 | pathogenic | -0.056 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/F | 0.9486 | likely_pathogenic | 0.9631 | pathogenic | -0.524 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/G | 0.7636 | likely_pathogenic | 0.763 | pathogenic | -1.472 | Destabilizing | None | None | None | None | N | 0.428445869 | None | None | N |
| R/H | 0.4073 | ambiguous | 0.4526 | ambiguous | -1.72 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/I | 0.7973 | likely_pathogenic | 0.8696 | pathogenic | 0.009 | Stabilizing | None | None | None | None | None | None | None | None | N |
| R/K | 0.2361 | likely_benign | 0.2486 | benign | -0.819 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/L | 0.7399 | likely_pathogenic | 0.7989 | pathogenic | 0.009 | Stabilizing | None | None | None | None | N | 0.426712286 | None | None | N |
| R/M | 0.826 | likely_pathogenic | 0.8772 | pathogenic | -0.381 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/N | 0.9356 | likely_pathogenic | 0.9415 | pathogenic | -0.576 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/P | 0.9467 | likely_pathogenic | 0.9377 | pathogenic | -0.335 | Destabilizing | None | None | None | None | N | 0.427752436 | None | None | N |
| R/Q | 0.2702 | likely_benign | 0.3257 | benign | -0.535 | Destabilizing | None | None | None | None | N | 0.428272511 | None | None | N |
| R/S | 0.9052 | likely_pathogenic | 0.9221 | pathogenic | -1.363 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/T | 0.8067 | likely_pathogenic | 0.858 | pathogenic | -0.943 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/V | 0.8598 | likely_pathogenic | 0.908 | pathogenic | -0.335 | Destabilizing | None | None | None | None | None | None | None | None | N |
| R/W | 0.6435 | likely_pathogenic | 0.6908 | pathogenic | -0.116 | Destabilizing | None | None | None | None | N | 0.428792586 | None | None | N |
| R/Y | 0.867 | likely_pathogenic | 0.8931 | pathogenic | 0.107 | Stabilizing | None | None | None | None | 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.