UniProtKB/Swiss-Prot P68133: Variant p.Asp294Val

Actin, alpha skeletal muscle
Gene: ACTA1
Chromosomal location: 1q42.13-q42.2
Variant information

Variant position:  294
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Aspartate (D) to Valine (V) at position 294 (D294V, p.Asp294Val).
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 acidic (D) to medium size and hydrophobic (V)
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

Involvement in disease:  Myopathy, congenital, with fiber-type disproportion (CFTD) [MIM:255310]: A genetically heterogeneous disorder in which there is relative hypotrophy of type 1 muscle fibers compared to type 2 fibers on skeletal muscle biopsy. However, these findings are not specific and can be found in many different myopathic and neuropathic conditions. {ECO:0000269|PubMed:15468086, ECO:0000269|PubMed:17387733}. Note=The disease is caused by mutations affecting the gene represented in this entry.
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 CFTD; results in decreased motility due to abnormal interactions between actin and tropomyosin with tropomyosin stabilized in the 'off' position; the mutant protein incorporates into actin filaments and does not result in increased actin aggregation or disruption of the sarcomere.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  294
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  377
The length of the canonical sequence.

Location on the sequence:   AGIHETTYNSIMKCDIDIRK  D LYANNVMSGGTTMYPGIADR
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.

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 2 – 377 Actin, alpha skeletal muscle, intermediate form
Chain 3 – 377 Actin, alpha skeletal muscle


Literature citations

Actin mutations are one cause of congenital fibre type disproportion.
Laing N.G.; Clarke N.F.; Dye D.E.; Liyanage K.; Walker K.R.; Kobayashi Y.; Shimakawa S.; Hagiwara T.; Ouvrier R.; Sparrow J.C.; Nishino I.; North K.N.; Nonaka I.;
Ann. Neurol. 56:689-694(2004)
Cited for: VARIANTS CFTD PRO-223; VAL-294 AND SER-334;

The pathogenesis of ACTA1-related congenital fiber type disproportion.
Clarke N.F.; Ilkovski B.; Cooper S.; Valova V.A.; Robinson P.J.; Nonaka I.; Feng J.-J.; Marston S.; North K.;
Ann. Neurol. 61:552-561(2007)
Cited for: CHARACTERIZATION OF VARIANT CFTD VAL-294;

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.