UniProtKB/SwissProt variant VAR

Variant information

Variant position:

454

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

LP/P [Disclaimer]

The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Arginine (R) to Tryptophan (W) at position 454 (R454W, p.Arg454Trp).

Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:

Change from large size and basic (R) to large size and aromatic (W)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-3

The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page

Variant description:

In MFM1; reveals a severe disturbance of filament-formation competence and filament-filament interactions; increased interaction with CRYAB.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs267607490 [ dbSNP | Ensembl ]

Sequence information

Variant position:

454

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

470

The length of the canonical sequence.

Location on the sequence:

EQRGSEVHTKKTVMIKTIET R DGEVVSEATQQQHEVL

The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         EQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Mouse                         EQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Rat                           EQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Pig                           EQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Bovine                        EQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Chicken                       DQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Xenopus laevis                EQRASEVHTKKTVMIKTIETRDGEVLSEASQQHQEIL

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	2 – 470	Desmin
Region	413 – 470	Tail

Literature citations

Conspicuous involvement of desmin tail mutations in diverse cardiac and skeletal myopathies.
Baer H.; Goudeau B.; Waelde S.; Casteras-Simon M.; Muecke N.; Shatunov A.; Goldberg Y.P.; Clarke C.; Holton J.L.; Eymard B.; Katus H.A.; Fardeau M.; Goldfarb L.; Vicart P.; Herrmann H.;
Hum. Mutat. 28:374-386(2007)
Cited for: VARIANTS MFM1 ILE-442; TRP-454 AND ILE-460; CHARACTERIZATION OF VARIANTS MFM1 ILE-442; MET-451; TRP-454 AND ILE-460;

Clinical, morphological and genetic studies in a cohort of 21 patients with myofibrillar myopathy.
Vattemi G.; Neri M.; Piffer S.; Vicart P.; Gualandi F.; Marini M.; Guglielmi V.; Filosto M.; Tonin P.; Ferlini A.; Tomelleri G.;
Acta Myol. 30:121-126(2011)
Cited for: VARIANTS MFM1 PHE-7 AND TRP-454;

alphaB-crystallin is a sensor for assembly intermediates and for the subunit topology of desmin intermediate filaments.
Sharma S.; Conover G.M.; Elliott J.L.; Der Perng M.; Herrmann H.; Quinlan R.A.;
Cell Stress Chaperones 22:613-626(2017)
Cited for: CHARACTERIZATION OF VARIANTS MFM1 MET-451 AND TRP-454; INTERACTION WITH CRYAB;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P17661: Variant p.Arg454Trp