NM_000527.5(LDLR):c.325T>C (p.Cys109Arg) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 12, 2021
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:: RCV002321915.2

Allele description [Variation Report for NM_000527.5(LDLR):c.325T>C (p.Cys109Arg)]

NM_000527.5(LDLR):c.325T>C (p.Cys109Arg)

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.325T>C (p.Cys109Arg)

HGVS:

NC_000019.10:g.11105231T>C
NG_009060.1:g.20851T>C
NM_000527.5:c.325T>CMANE SELECT
NM_001195798.2:c.325T>C
NM_001195799.2:c.202T>C
NM_001195800.2:c.314-2161T>C
NM_001195803.2:c.314-1334T>C
NP_000518.1:p.Cys109Arg
NP_000518.1:p.Cys109Arg
NP_001182727.1:p.Cys109Arg
NP_001182728.1:p.Cys68Arg
LRG_274t1:c.325T>C
LRG_274:g.20851T>C
NC_000019.9:g.11215907T>C
NM_000527.4(LDLR):c.325T>C
NM_000527.4:c.325T>C
P01130:p.Cys109Arg
c.325T>C

Protein change:

C109R

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001701; UniProtKB: P01130#VAR_005316; dbSNP: rs140807148

NCBI 1000 Genomes Browser:

rs140807148

Molecular consequence:

NM_001195800.2:c.314-2161T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1334T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.325T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.325T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.202T>C - 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
SCV002611132	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 12, 2021)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 11139254, 11313767, 12009418, 1301956, 14974088, 16250003, 16314194, 20145306, 22698793, 23375686, 24627126, 32104752 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002611132

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 12, 2021)

germline

clinical testing

PubMed (12)
[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

Eight novel LDL receptor gene mutations among patients under LDL apheresis in Dresden and Leipzig.

Bochmann H, Geisel J, Herrmann W, Purcz T, Reuter W, Julius U, Metzler W, Bergmann S, Jaross W, Gehrisch S.

Hum Mutat. 2001;17(1):76-7.

PubMed [citation]

PMID:: 11139254

A molecular genetic service for diagnosing individuals with familial hypercholesterolaemia (FH) in the United Kingdom.

Heath KE, Humphries SE, Middleton-Price H, Boxer M.

Eur J Hum Genet. 2001 Apr;9(4):244-52.

PubMed [citation]

PMID:: 11313767

See all PubMed Citations (12)

Details of each submission

From Ambry Genetics, SCV002611132.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

The p.C109R pathogenic mutation (also known as c.325T>C), located in coding exon 4 of the LDLR gene, results from a T to C substitution at nucleotide position 325. The cysteine at codon 109 is replaced by arginine, an amino acid with highly dissimilar properties. Pathogenic LDLR mutations that result in the substitution or generation of cysteine residues within the cysteine-rich LDLR class A repeats and EGF-like domains are common in familial hypercholesterolemia (FH) (Villéger L. Hum Mutat. 2002;20(2):81-7). This alteration, also known as FH Munster-1 or p.C88R, has been reported in individuals with familial hypercholesterolimia (FH) from a number of ethnic groups (Hobbs HH et al. Hum Mutat. 1992;1:445-66; Fouchier SW et al. Hum Mutat. 2005;26:550-6; Robles-Osorio L et al. Arch Med Res. 2006;37:102-8; Tichý L et al. Atherosclerosis. 2012;223:401-8). A different nucleotide change resulting in the same amino acid alteration (c.324_325delGTinsTC) has also been detected in patients with FH (Heath KE et al. Eur J Hum Genet. 2001;9:244-52; Chmara M et al. J Appl Genet. 2010;51:95-106). In addition, alterations at the same amino acid position, p.C109S and p.C109Y (also known as p.C88S and p.C88Y, respectively), have also been reported in association with FH (Pisciotta L et al. Biochim Biophys Acta. 2002;1587:7-11; Bertolini S et al. Atherosclerosis. 2013;227:342-8; Heath KE et al. Eur J Hum Genet. 2001;9:244-52; Chmara M et al. J Appl Genet. 2010;51:95-106). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	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: Oct 20, 2024

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