UniProtKB/SwissProt variant VAR

Variant information

Variant position:

568

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 Leucine (L) to Valine (V) at position 568 (L568V, p.Leu568Val).

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

Involvement in disease:

Familial hypercholesterolemia (FH) [MIM:143890]: A common autosomal dominant disorder characterized by elevated serum low-density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. The disorder occurs in 2 clinical forms: a mild form that becomes evident in the fourth or fifth decade in individuals carrying heterozygous LDLR mutations; a more severe form that usually manifests in the first two decades of life in individuals with homozygous LDLR mutations. {ECO:0000269|PubMed:10090484, ECO:0000269|PubMed:10206683, ECO:0000269|PubMed:10422803, ECO:0000269|PubMed:10447263, ECO:0000269|PubMed:10532689, ECO:0000269|PubMed:10660340, ECO:0000269|PubMed:10882754, ECO:0000269|PubMed:10978268, ECO:0000269|PubMed:10980548, ECO:0000269|PubMed:11298688, ECO:0000269|PubMed:11462246, ECO:0000269|PubMed:1446662, ECO:0000269|PubMed:1464748, ECO:0000269|PubMed:17142622, ECO:0000269|PubMed:17347910, ECO:0000269|PubMed:1867200, ECO:0000269|PubMed:19318025, ECO:0000269|PubMed:19319977, ECO:0000269|PubMed:22160468, ECO:0000269|PubMed:22509010, ECO:0000269|PubMed:2318961, ECO:0000269|PubMed:24529145, ECO:0000269|PubMed:25378237, ECO:0000269|PubMed:25545329, ECO:0000269|PubMed:2569482, ECO:0000269|PubMed:2726768, ECO:0000269|PubMed:3263645, ECO:0000269|PubMed:3955657, ECO:0000269|PubMed:7550239, ECO:0000269|PubMed:7573037, ECO:0000269|PubMed:7583548, ECO:0000269|PubMed:7635461, ECO:0000269|PubMed:7635482, ECO:0000269|PubMed:7649546, ECO:0000269|PubMed:7649549, ECO:0000269|PubMed:8168830, ECO:0000269|PubMed:8347689, ECO:0000269|PubMed:8462973, ECO:0000269|PubMed:8664907, ECO:0000269|PubMed:8740918, ECO:0000269|PubMed:9026534, ECO:0000269|PubMed:9104431, ECO:0000269|PubMed:9143924, ECO:0000269|PubMed:9254862, ECO:0000269|PubMed:9259195, ECO:0000269|PubMed:9452094, ECO:0000269|PubMed:9452095, ECO:0000269|PubMed:9452118, ECO:0000269|PubMed:9654205, ECO:0000269|PubMed:9678702, ECO:0000269|PubMed:9852677, ECO:0000269|Ref.71}. 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 FH; Japanese patient.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs746959386 [ dbSNP | Ensembl ]

Sequence information

Variant position:

568

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

Protein sequence length:

860

The length of the canonical sequence.

Location on the sequence:

NGVDIYSLVTENIQWPNGIT L DLLSGRLYWVDSKLHSISSI

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                         NGVDIYSLVTENIQWPNGITLDLLSGRLYWVDSKLHSISSI

Mouse                         NGVDIHSLVTENIQWPNGITLDLSSGRLYWVDSKLHSISSI

Rat                           NGVDIYSLVTEDIQWPNGITLDLPSGRLYWVDSKLHSISSI

Bovine                        NGVDVYSLVTEDIQWPNGITLDLSGGRLYWVDSKLHSISSI

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	22 – 860	Low-density lipoprotein receptor
Topological domain	22 – 788	Extracellular
Repeat	529 – 572	LDL-receptor class B 4
Beta strand	563 – 569

Literature citations

Identification of recurrent and novel mutations in the LDL receptor gene in Japanese familial hypercholesterolemia.
Hattori H.; Nagano M.; Iwata F.; Homma Y.; Egashira T.; Okada T.;
Hum. Mutat. 14:87-87(1999)
Cited for: VARIANTS FH SER-338; LEU-403; THR-431; VAL-568 AND LYS-714;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P01130: Variant p.Leu568Val