NM_000527.5(LDLR):c.2054C>G (p.Pro685Arg) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 16, 2023
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:: RCV004369053.1

Allele description [Variation Report for NM_000527.5(LDLR):c.2054C>G (p.Pro685Arg)]

NM_000527.5(LDLR):c.2054C>G (p.Pro685Arg)

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.2054C>G (p.Pro685Arg)

HGVS:

NC_000019.10:g.11120436C>G
NG_009060.1:g.36056C>G
NM_000527.5:c.2054C>GMANE SELECT
NM_001195798.2:c.2054C>G
NM_001195799.2:c.1931C>G
NM_001195800.2:c.1550C>G
NM_001195803.2:c.1606+203C>G
NP_000518.1:p.Pro685Arg
NP_000518.1:p.Pro685Arg
NP_001182727.1:p.Pro685Arg
NP_001182728.1:p.Pro644Arg
NP_001182729.1:p.Pro517Arg
LRG_274t1:c.2054C>G
LRG_274:g.36056C>G
LRG_274p1:p.Pro685Arg
NC_000019.9:g.11231112C>G
NM_000527.4:c.2054C>G

Protein change:

P517R

Molecular consequence:

NM_001195803.2:c.1606+203C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.2054C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.2054C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1931C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1550C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

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Homo sapiens APOBEC1 complementation factor (A1CF), transcript variant 2, mRNA
Homo sapiens APOBEC1 complementation factor (A1CF), transcript variant 2, mRNA
gi|20357574|ref|NM_138932.1|

Nucleotide
hypothetical protein L916_18460 [Phytophthora nicotianae]
hypothetical protein L916_18460 [Phytophthora nicotianae]
gi|567977614|gb|ETL28112.1||gnl|WGS |L916_18460T0

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005035885	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Nov 16, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005035885

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Nov 16, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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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

Identification of a point mutation in growth factor repeat C of the low density lipoprotein-receptor gene in a patient with homozygous familial hypercholesterolemia that affects ligand binding and intracellular movement of receptors.

Soutar AK, Knight BL, Patel DD.

Proc Natl Acad Sci U S A. 1989 Jun;86(11):4166-70.

PubMed [citation]

PMID:: 2726768
PMCID:: PMC287410

Details of each submission

From Ambry Genetics, SCV005035885.1

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

Description

The p.P685R variant (also known as c.2054C>G), located in coding exon 14 of the LDLR gene, results from a C to G substitution at nucleotide position 2054. The proline at codon 685 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with LDLR-related disease (Ambry internal data). This variant is also considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Another alteration at the same codon, p.P685L (c.2054C>T), has been described in association with familial hypercholesterolemia (FH) (Soutar AK et al. Proc Natl Acad Sci U S A, 1989 Jun;86:4166-70). This amino acid position is highly 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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