UniProtKB/Swiss-Prot P17661: Variant p.Leu338Arg

Desmin
Gene: DES
Chromosomal location: 2q35
Variant information

Variant position:  338
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Leucine (L) to Arginine (R) at position 338 (L338R, p.Leu338Arg).
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 medium size and hydrophobic (L) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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

Involvement in disease:  Myopathy, myofibrillar, 1 (MFM1) [MIM:601419]: A neuromuscular disorder characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias, restrictive heart failure, and by myofibrillar destruction with intracytoplasmic accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells. Note=The disease is caused by mutations affecting the gene represented in this entry. Mutations in the DES gene are associated with a variable clinical phenotype which encompasses isolated myopathies, pure cardiac phenotypes (including dilated cardiomyopathy, restrictive cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy), cardiac conduction disease, and combinations of these disorders. If both cardiologic and neurologic features occur, they can manifest in any order, as cardiologic features can precede, occur simultaneously with, or follow manifestation of generalized neuromuscular disease (PubMed:19879535).
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In MFM1; results in the formation of a filamentous network disrupted by multiple breaks and clumps or large aggregates.
Any additional useful information about the variant.



Sequence information

Variant position:  338
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:   KQEMMEYRHQIQSYTCEIDA  L KGTNDSLMRQMRELEDRFAS
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                         KQEMMEYRHQIQSYTCEIDALKGTNDSLMRQMRELEDRFAS

Mouse                         KQEMMEYRHQIQSYTCEIDALKGTNDSLMRQMRELEDRFAS

Rat                           KQEMMEYRHQIQSYTCEIDALKGTNDSLMRQMRELEDRFAS

Pig                           KQEMMEYRHQIQSYTCEIDALKGTNDSLMRQMRELEDRFAS

Bovine                        KQEMMEYRHQIQSYTCEIDALKGTNDSLMRQMRELEDRFAS

Dog                           KQEMMEYRHQIQSYTCEIDALKGTNDSLMRQMREMEDRFAS

Chicken                       KQEMLEYRHQIQSYTCEIDALKGTNDSLMRQMREMEERFAG

Xenopus laevis                KQEMMEYRHQIQSYTCEIDALKGTNDSLMRQMRDLEEKFSG

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.

TypePositionsDescription
Chain 1 – 470 Desmin
Region 109 – 412 Rod
Region 296 – 412 Coil 2B


Literature citations

Variable pathogenic potentials of mutations located in the desmin alpha-helical domain.
Goudeau B.; Rodrigues-Lima F.; Fischer D.; Casteras-Simon M.; Sambuughin N.; de Visser M.; Laforet P.; Ferrer X.; Chapon F.; Sjoberg G.; Kostareva A.; Sejersen T.; Dalakas M.C.; Goldfarb L.G.; Vicart P.;
Hum. Mutat. 27:906-913(2006)
Cited for: VARIANTS MFM1 ARG-338; TYR-399 AND LYS-401; VARIANT VAL-213; CHARACTERIZATION OF VARIANTS MFM1 ARG-338; PRO-360; ILE-393; TYR-399 AND LYS-401; CHARACTERIZATION OF VARIANT VAL-213;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.