UniProtKB/Swiss-Prot P18206: Variant p.Arg975Trp

Vinculin
Gene: VCL
Chromosomal location: 10q11.2-qter
Variant information

Variant position:  975
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 Arginine (R) to Tryptophan (W) at position 975 (R975W, p.Arg975Trp).
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 CMD1W; significantly alters metavinculin-mediated cross-linking of actin filaments.
Any additional useful information about the variant.



Sequence information

Variant position:  975
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1134
The length of the canonical sequence.

Location on the sequence:   LMPSNQPVNQPILAAAQSLH  R EATKWSSKGNDIIAAAKRMA
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                         LMPSNQPVNQPILAAAQSLHREATKWSSKGNDIIAAAKRMA

Mouse                         -------------------------WSSKGNDIIAAAKRMA

Rat                           -------------------------WSSKGNDIIAAAKRMA

Pig                           LMPSSQPVNQPILAAAQSLHREATKWSSKGNDIIAAAKRMA

Chicken                       LMPTNQPVNQPILAAAQSLHREATKWSSKGNDIIAAAKRMA

Caenorhabditis elegans        -------------------------WSSQENDIVAAAKRMA

Drosophila                    -------------------------WSSKDNEIIAAAKRMA

Slime mold                    --------------------------GTPLGILVQLSDEIA

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 – 1134 Vinculin
Region 879 – 1134 C-terminal tail
Alternative sequence 296 – 1134 Missing. In isoform 3.
Alternative sequence 916 – 983 Missing. In isoform 1.
Helix 964 – 977


Literature citations

Metavinculin mutations alter actin interaction in dilated cardiomyopathy.
Olson T.M.; Illenberger S.; Kishimoto N.Y.; Huttelmaier S.; Keating M.T.; Jockusch B.M.;
Circulation 105:431-437(2002)
Cited for: VARIANTS CMD1W LEU-954 DEL AND TRP-975; CHARACTERIZATION OF VARIANT CMD1W TRP-975;

Identification of a metavinculin missense mutation, R975W, associated with both hypertrophic and dilated cardiomyopathy.
Vasile V.C.; Will M.L.; Ommen S.R.; Edwards W.D.; Olson T.M.; Ackerman M.J.;
Mol. Genet. Metab. 87:169-174(2006)
Cited for: VARIANT CMD1W TRP-975; VARIANTS VAL-934 AND ALA-943;

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.