UniProtKB/SwissProt variant VAR

Variant information

Variant position:

42

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 Histidine (H) to Tyrosine (Y) at position 42 (H42Y, p.His42Tyr).

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 polar (H) to large size and aromatic (Y)

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

Variant description:

In NEM3; severe.

Any additional useful information about the variant.

Sequence information

Variant position:

42

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:

GFAGDDAPRAVFPSIVGRPR H QGVMVGMGQKDSYVGDEAQS

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
Modified residue	46 – 46	Methionine (R)-sulfoxide
Modified residue	49 – 49	Methionine (R)-sulfoxide
Cross	52 – 52	Isoglutamyl lysine isopeptide (Lys-Glu) (interchain with E-272); by Vibrio toxins RtxA and VgrG1

Literature citations

Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy.
Nowak K.J.; Wattanasirichaigoon D.; Goebel H.H.; Wilce M.; Pelin K.; Donner K.; Jacob R.L.; Hubner C.; Oexle K.; Anderson J.R.; Verity C.M.; North K.N.;
Nat. Genet. 23:208-212(1999)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS NEM3 TYR-42; PRO-96; SER-117; VAL-134; ASP-184; CYS-185; HIS-258; VAL-261; LEU-265; LYS-282; GLY-288 AND PHE-372; VARIANTS MPCETM ARG-17 AND LEU-165;

Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-actin gene mutations.
Agrawal P.B.; Strickland C.D.; Midgett C.; Morales A.; Newburger D.E.; Poulos M.A.; Tomczak K.K.; Ryan M.M.; Iannaccone S.T.; Crawford T.O.; Laing N.G.; Beggs A.H.;
Ann. Neurol. 56:86-96(2004)
Cited for: VARIANTS NEM3 LEU-37; LEU-40; TYR-42; ARG-43; ASN-66; LEU-75; ARG-75; LEU-77; ALA-79; LYS-85; ALA-136; ASP-148; GLY-181; ASP-184; GLY-185; SER-199; GLY-226; VAL-229; ILE-229; ARG-248; ASP-253; CYS-270; HIS-281; LYS-282; GLY-288 AND GLN-375;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P68133: Variant p.His42Tyr