LDLRAP1 R238W - GET-Evidence

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LDLRAP1 R238W

(LDLRAP1 Arg238Trp)


You are viewing an old version of this page that was saved on March 13, 2010 at 9:55pm by Madeleine Ball.

Short summary

This variant was seen in a homozygous fashion (together with a homozygous frameshift yielding a termination codon at codon 219) in two male English siblings who were diagnosed with recessive familial Hypercholesterolemia at ages 7 and 9.

Variant evidence
Computational 2

NBLOSUM = 4, gene is associated with this disease.

Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

recessive

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr1:25890247: 3.5% (374/10758) in EVS
  • T @ chr1:25762833: 1.6% (2/122) in GET-Evidence
  • Frequency shown in summary reports: 3.5% (374/10758)

Publications
 

Eden ER, Patel DD, Sun XM, Burden JJ, Themis M, Edwards M, Lee P, Neuwirth C, Naoumova RP, Soutar AK. Restoration of LDL receptor function in cells from patients with autosomal recessive hypercholesterolemia by retroviral expression of ARH1. J Clin Invest. 2002 Dec;110(11):1695-702. PubMed PMID: 12464675; PubMed Central PMCID: PMC151635.

This variant was seen in a homozygous fashion together with a homozygous frameshift yielding a termination codon at codon 219. Both male English siblings were diagnosed with recessive familial Hypercholesterolemia at ages 7 and 9. Their normal sister had neither variant and their (presumed?) normal mother was heterozygous for both alleles.

Hubacek JA, Hyatt T. ARH missense polymorphisms and plasma cholesterol levels. Clin Chem Lab Med. 2004;42(9):989-90. PubMed PMID: 15497461.

In a comparison of high and low plasma cholesterol groups (100 males in each), the authors did not see a higher concentration of this variant in the high cholesterol group. They conclude that this polymorphism is unlikely to be an important genetic determinant of plasma cholesterol levels in Caucasians. Counting chromosomes, high+: 5, high-: 195, low+: 9, low-: 191.

Genomes
 

snp-6

 

Other external references
 

    PolyPhen-2
  • Score: 0.961 (probably damaging)
    Web search results (0 hits -- see all)

Other in silico analyses
 

  • NBLOSUM100 score = 7
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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