NM_000527.5(LDLR):c.251C>G (p.Pro84Arg) AND Familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 9, 2022
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:: RCV002518473.4

Allele description [Variation Report for NM_000527.5(LDLR):c.251C>G (p.Pro84Arg)]

NM_000527.5(LDLR):c.251C>G (p.Pro84Arg)

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.251C>G (p.Pro84Arg)

Other names:

NM_000527.5(LDLR):c.251C>G; p.Pro84Arg

HGVS:

NC_000019.10:g.11102724C>G
NG_009060.1:g.18344C>G
NM_000527.5:c.251C>GMANE SELECT
NM_001195798.2:c.251C>G
NM_001195799.2:c.190+2379C>G
NM_001195800.2:c.251C>G
NM_001195803.2:c.251C>G
NP_000518.1:p.Pro84Arg
NP_001182727.1:p.Pro84Arg
NP_001182729.1:p.Pro84Arg
NP_001182732.1:p.Pro84Arg
LRG_274:g.18344C>G
NC_000019.9:g.11213400C>G
c.251C>G

Protein change:

P84R

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001155; dbSNP: rs875989892

NCBI 1000 Genomes Browser:

rs875989892

Molecular consequence:

NM_001195799.2:c.190+2379C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.251C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.251C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.251C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.251C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial hypercholesterolemia
Identifiers:: MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003258651	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 9, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22883975, 16159606, 33740630, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003258651

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 9, 2022)

germline

clinical testing

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

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

Genetic analysis of familial hypercholesterolaemia in Western Australia.

Hooper AJ, Nguyen LT, Burnett JR, Bates TR, Bell DA, Redgrave TG, Watts GF, van Bockxmeer FM.

Atherosclerosis. 2012 Oct;224(2):430-4. doi: 10.1016/j.atherosclerosis.2012.07.030. Epub 2012 Jul 27.

PubMed [citation]

PMID:: 22883975

Genetic screening protocol for familial hypercholesterolemia which includes splicing defects gives an improved mutation detection rate.

Graham CA, McIlhatton BP, Kirk CW, Beattie ED, Lyttle K, Hart P, Neely RD, Young IS, Nicholls DP.

Atherosclerosis. 2005 Oct;182(2):331-40.

PubMed [citation]

PMID:: 16159606

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003258651.3

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

Description

This variant disrupts the p.Pro84 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been observed in individuals with LDLR-related conditions (PMID: 22883975, 33740630), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LDLR protein function. ClinVar contains an entry for this variant (Variation ID: 251095). This variant is also known as P63R. This missense change has been observed in individuals with familial hypercholesterolemia (PMID: 16159606, 33740630; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 84 of the LDLR protein (p.Pro84Arg).

#	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: Feb 25, 2025

ClinVar

Relating variation to medicine