UniProtKB/SwissProt variant VAR

Variant information

Variant position:

165

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 Valine (V) to Methionine (M) at position 165 (V165M, p.Val165Met).

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:

Similar physico-chemical property. Both residues are medium size and hydrophobic.

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

BLOSUM score:

1

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 NEM3; results in sequestration of sarcomeric and Z line proteins into intranuclear aggregates; there is some evidence of muscle regeneration suggesting a compensatory effect.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121909522 [ dbSNP | Ensembl ]

Sequence information

Variant position:

165

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:

YASGRTTGIVLDSGDGVTHN V PIYEGYALPHAIMRLDLAGR

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.

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

Literature citations

Evidence for a dominant-negative effect in ACTA1 nemaline myopathy caused by abnormal folding, aggregation and altered polymerization of mutant actin isoforms.
Ilkovski B.; Nowak K.J.; Domazetovska A.; Maxwell A.L.; Clement S.; Davies K.E.; Laing N.G.; North K.N.; Cooper S.T.;
Hum. Mol. Genet. 13:1727-1743(2004)
Cited for: VARIANTS NEM3 ILE-68; LYS-74; SER-117; MET-138; LEU-165; MET-165; GLY-185; CYS-270 AND LEU-359;

Autosomal dominant nemaline myopathy with intranuclear rods due to mutation of the skeletal muscle ACTA1 gene: clinical and pathological variability within a kindred.
Hutchinson D.O.; Charlton A.; Laing N.G.; Ilkovski B.; North K.N.;
Neuromuscul. Disord. 16:113-121(2006)
Cited for: VARIANT NEM3 MET-165;

Intranuclear rod myopathy: molecular pathogenesis and mechanisms of weakness.
Domazetovska A.; Ilkovski B.; Kumar V.; Valova V.A.; Vandebrouck A.; Hutchinson D.O.; Robinson P.J.; Cooper S.T.; Sparrow J.C.; Peckham M.; North K.N.;
Ann. Neurol. 62:597-608(2007)
Cited for: CHARACTERIZATION OF VARIANT NEM3 MET-165;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P68133: Variant p.Val165Met