UniProtKB/Swiss-Prot P08519: Variant p.Trp1685Arg

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 1685 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B The variants are classified into three categories: LP/P, LB/B and US.

• LP/P: likely pathogenic or pathogenic.
• LB/B: likely benign or benign.
• US: uncertain significance

Residue change: From Tryptophan (W) to Arginine (R) at position 1685 (W1685R, p.Trp1685Arg). 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 aromatic (W) to large size and basic (R) 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
Polymorphism: LPA genetic variants, including variations in the number of Kringle domains, define the lipoprotein(a) quantitative trait locus (LPAQTL) and influence lipoprotein(a) levels in plasma [MIM:618807]. Depending on the individual, the encoded protein contains 2-43 copies of kringle IV-2 repeats. Often the assignement of amino acids in lipoprotein(a) is based on a long allele that contains 37 copies of the kringle-type repeats (PubMed:3670400). The reference allele represented here contains 15 copies of the kringle-type repeats. Additional information on the polymorphism described.
Variant description: Loss of lysine-sepharose binding. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs1211014575 [ dbSNP | Ensembl ]

Sequence information

Variant position: 1685 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 2040 The length of the canonical sequence.
Location on the sequence: CRNPDADTGPWCFTMDPSIR W EYCNLTRCSDTEGTVVAPPT 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	20 – 2040	Apolipoprotein(a)
Domain	1615 – 1693	Kringle 15
Glycosylation	1689 – 1689	N-linked (GlcNAc...) asparagine
Disulfide bond	1616 – 1693
Disulfide bond	1665 – 1688
Beta strand	1685 – 1689

Literature citations

A single point mutation (Trp72-->Arg) in human apo(a) kringle 4-37 associated with a lysine binding defect in Lp(a).
Scanu A.M.; Pfaffinger D.; Lee J.C.; Hinman J.;
Biochim. Biophys. Acta 1227:41-45(1994)
Cited for: VARIANT ARG-1685;