Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:

Currentness:

LDLRAP1 R238W

(LDLRAP1 Arg238Trp)

This variant was seen in a homozygous fashion in siblings with familial hypercholesterolemia who also had a frameshift mutation in the same gene. Hubacek et al. studied the frequency of this variant in high and low cholesterol groups and conclude that this variant has little effect, if any, on cholesterol levels.

Variant evidence
Computational	2	NBLOSUM = 4, gene is associated with this disease.
		NBLOSUM = 4, gene is associated with this disease.
Functional	-

Case/Control	-1	Data from Hubacek et al. suggests this variant does not have a strong effect, if any. See Hubacek JA et al. 2004 (15497461).

Familial	-


Clinical importance
Severity	1	If this variant has an effect, it is not very significant.
		If this variant has an effect, it is not very significant.
Treatability	3	Treatment with statins.
		Treatment with statins.
Penetrance	-

Insufficiently evaluated pathogenic

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

recessive

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

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.

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

Other external references

dbSNP

rs41291058
www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi

GeneTests

GeneTests records for the LDLRAP1 gene
Familial Hypercholesterolemia, Autosomal Recessive
www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/LDLRAP1

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

Nov 29 2012 Genome Importing Robot added CGI sample GS01669-DNA_B03 from PGP sample 14427241 view
Nov 29 2012 Genome Importing Robot added CGI sample GS01173-DNA_B07 from PGP sample 61499538 view
Sep 1 2012 Natalia Trikoz edited variant summary view
Sep 1 2012 Natalia Trikoz edited article 15497461 summary view
Sep 1 2012 Natalia Trikoz edited article 12464675 summary view
Jun 22 2011 Genome Importing Robot removed Stephen Quake view
Dec 5 2010 Genome Importing Robot added CGI sample GS00253-DNA_A02_200_37 view
Mar 13 2010 Madeleine Ball edited variant summary view
Mar 13 2010 Madeleine Ball edited variant summary view
Mar 13 2010 Madeleine Ball edited OR figures for Familial Hypercholesterolemia, Autosomal Recessive from article 15497461 view
Mar 13 2010 Madeleine Ball added OR figures for Familial Hypercholesterolemia, Autosomal Recessive from article 15497461 view
Mar 13 2010 Madeleine Ball edited article 15497461 summary view
Mar 13 2010 Madeleine Ball edited variant summary view
Mar 13 2010 Madeleine Ball edited article 15497461 summary view
Mar 13 2010 Madeleine Ball edited variant summary view
Mar 13 2010 Madeleine Ball added article 15497461 view
Jan 14 2010 Abraham Rosenbaum edited article 12464675 summary view
Jan 14 2010 Abraham Rosenbaum edited variant summary view
Jan 14 2010 Abraham Rosenbaum added article 12464675 view
Dec 27 2009 Genome Importing Robot added Stephen Quake view
Dec 27 2009 Genome Importing Robot added variant view

LDLRAP1 R238W - GET-Evidence