NM_000527.5(LDLR):c.1525A>G (p.Lys509Glu) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 8, 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:: RCV004020967.1

Allele description [Variation Report for NM_000527.5(LDLR):c.1525A>G (p.Lys509Glu)]

NM_000527.5(LDLR):c.1525A>G (p.Lys509Glu)

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.1525A>G (p.Lys509Glu)

HGVS:

NC_000019.10:g.11113701A>G
NG_009060.1:g.29321A>G
NM_000527.5:c.1525A>GMANE SELECT
NM_001195798.2:c.1525A>G
NM_001195799.2:c.1402A>G
NM_001195800.2:c.1021A>G
NM_001195803.2:c.1144A>G
NP_000518.1:p.Lys509Glu
NP_000518.1:p.Lys509Glu
NP_001182727.1:p.Lys509Glu
NP_001182728.1:p.Lys468Glu
NP_001182729.1:p.Lys341Glu
NP_001182732.1:p.Lys382Glu
LRG_274t1:c.1525A>G
LRG_274:g.29321A>G
LRG_274p1:p.Lys509Glu
NC_000019.9:g.11224377A>G
NM_000527.4:c.1525A>G
c.1525A>G

Protein change:

K341E

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000476; dbSNP: rs879254931

NCBI 1000 Genomes Browser:

rs879254931

Molecular consequence:

NM_000527.5:c.1525A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1525A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1402A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1021A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1144A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Synechocystis sp. MW42 16S ribosomal RNA gene, partial sequence
Synechocystis sp. MW42 16S ribosomal RNA gene, partial sequence
gi|1244552991|gb|KX962095.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003976995	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jun 8, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 11810272, 29353225, 30637778, 30827231, 30971288, 35913489 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003976995

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jun 8, 2023)

germline

clinical testing

PubMed (6)
[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

The molecular basis of familial hypercholesterolemia in The Netherlands.

Fouchier SW, Defesche JC, Umans-Eckenhausen MW, Kastelein JP.

Hum Genet. 2001 Dec;109(6):602-15. Epub 2001 Nov 9.

PubMed [citation]

PMID:: 11810272

Spectrum of mutations in index patients with familial hypercholesterolemia in Singapore: Single center study.

Pek SLT, Dissanayake S, Fong JCW, Lin MX, Chan EZL, Tang JI, Lee CW, Ong HY, Sum CF, Lim SC, Tavintharan S.

Atherosclerosis. 2018 Feb;269:106-116. doi: 10.1016/j.atherosclerosis.2017.12.028. Epub 2017 Dec 27.

PubMed [citation]

PMID:: 29353225

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV003976995.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The c.1525A>G (p.K509E) alteration is located in exon 10 (coding exon 10) of the LDLR gene. This alteration results from a A to G substitution at nucleotide position 1525, causing the lysine (K) at amino acid position 509 to be replaced by a glutamic acid (E). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been reported in several individuals with a clinical diagnosis or suspicious of familial hypercholesterolemia (Fouchier, 2001; Pek, 2018; Cui, 2019; Yang, 2019; Lee, 2019; Sustar, 2022). This amino acid position is not well conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely 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: Oct 8, 2024

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