UniProtKB/SwissProt variant VAR

Variant information

Variant position:

248

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

Type of variant:

LP/P [Disclaimer]

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 Cysteine (C) to Tyrosine (Y) at position 248 (C248Y, p.Cys248Tyr).

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 (C) 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 FHCL1; British patient.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs879254663 [ dbSNP | Ensembl ]

Sequence information

Variant position:

248

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:

EENCAVATCRPDEFQCSDGN C IHGSRQCDREYDCKDMSDEV

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                         EENCAVATCRPDEFQCSDGNCIHGSRQCDREYDCKDMSDEV

Mouse                         EEHCAVATCRPDEFQCADGSCIHGSRQCDREHDCKDMSDEL

Rat                           EENCAVTTCRPDEFQCADGSCIHGSRQCDREHDCKDMSDEL

Bovine                        EENCAVATCRPDEFQCSDGTCIHGSRQCDREPDCKDLSDEL

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
Domain	234 – 272	LDL-receptor class A 6
Disulfide bond	236 – 248
Disulfide bond	243 – 261
Alternative sequence	105 – 272	Missing. In isoform 3.
Beta strand	247 – 249

Literature citations

Characterization of mutations in the low density lipoprotein (LDL)-receptor gene in patients with homozygous familial hypercholesterolemia, and frequency of these mutations in FH patients in the United Kingdom.
Webb J.C.; Sun X.-M.; McCarthy S.N.; Neuwirth C.; Thompson G.R.; Knigh B.; Soutar A.K.;
J. Lipid Res. 37:368-381(1996)
Cited for: VARIANTS FHCL1 ARG-197; TYR-248; ALA-301; TRP-302 AND PRO-350;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P01130: Variant p.Cys248Tyr