NM_000527.5(LDLR):c.1217G>A (p.Arg406Gln) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 5, 2016
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002354607.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1217G>A (p.Arg406Gln)]

NM_000527.5(LDLR):c.1217G>A (p.Arg406Gln)

Gene:

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.1217G>A (p.Arg406Gln)

Other names:

NM_000527.5(LDLR):c.1217G>A

HGVS:

NC_000019.10:g.11113308G>A
NG_009060.1:g.28928G>A
NM_000527.5:c.1217G>AMANE SELECT
NM_001195798.2:c.1217G>A
NM_001195799.2:c.1094G>A
NM_001195800.2:c.713G>A
NM_001195803.2:c.836G>A
NP_000518.1:p.Arg406Gln
NP_000518.1:p.Arg406Gln
NP_001182727.1:p.Arg406Gln
NP_001182728.1:p.Arg365Gln
NP_001182729.1:p.Arg238Gln
NP_001182732.1:p.Arg279Gln
LRG_274t1:c.1217G>A
LRG_274:g.28928G>A
NC_000019.9:g.11223984G>A
NM_000527.4(LDLR):c.1217G>A
NM_000527.4:c.1217G>A
P01130:p.Arg406Gln
c.1217G>A

Protein change:

R238Q

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000650; UniProtKB: P01130#VAR_013954; dbSNP: rs552422789

NCBI 1000 Genomes Browser:

rs552422789

Molecular consequence:

NM_000527.5:c.1217G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1217G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1094G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.713G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.836G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002656838	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (May 5, 2016)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10882754, 16466730, 17094996, 25741862 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002656838

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(May 5, 2016)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia.

Thiart R, Scholtz CL, Vergotine J, Hoogendijk CF, de Villiers JN, Nissen H, Brusgaard K, Gaffney D, Hoffs MS, Vermaak WJ, Kotze MJ.

J Med Genet. 2000 Jul;37(7):514-9.

PubMed [citation]

PMID:: 10882754
PMCID:: PMC1734636

The discrete and combined effect of SREBP-2 and SCAP isoforms in the control of plasma lipids among familial hypercholesterolaemia patients.

Durst R, Jansen A, Erez G, Bravdo R, Butbul E, Ben Avi L, Shpitzen S, Lotan C, Leitersdorf E, Defesche J, Friedlander Y, Meiner V, Miserez AR.

Atherosclerosis. 2006 Dec;189(2):443-50. Epub 2006 Feb 8.

PubMed [citation]

PMID:: 16466730

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002656838.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The p.R406Q variant (also known as c.1217G>A), located in coding exon 9 of the LDLR gene, results from a G to A substitution at nucleotide position 1217. The arginine at codon 406 is replaced by glutamine, an amino acid with highly similar properties. This variant has been described in unrelated individuals reported to have familial hypercholesterolemia (Thiart R et al. J Med Genet. 2000;37(7):514-9; Durst R et al. Atherosclerosis. 2006;189(2):443-50; Tosi I et al. Atherosclerosis. 2007;194(1):102-11 (reported as p.R385Q in these publications); Pek et al. Atherosclerosis. 2017; [Epub ahead of print]). Other alterations affecting the the same amino acid (p.R406P, c.1217G>C and p.R406W, c.1216C>T) have also been reported in association with hypercholesterolemia (Tosi I et al. Atherosclerosis. 2007;194(1):102-11 (reported as p.R385P); Benito-Vicente A et al. Genet Med. 2015;17(12):980-8). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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