NM_000527.5(LDLR):c.1510A>G (p.Lys504Glu) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 13, 2024
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:: RCV004526622.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1510A>G (p.Lys504Glu)]

NM_000527.5(LDLR):c.1510A>G (p.Lys504Glu)

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.1510A>G (p.Lys504Glu)

HGVS:

NC_000019.10:g.11113686A>G
NG_009060.1:g.29306A>G
NM_000527.5:c.1510A>GMANE SELECT
NM_001195798.2:c.1510A>G
NM_001195799.2:c.1387A>G
NM_001195800.2:c.1006A>G
NM_001195803.2:c.1129A>G
NP_000518.1:p.Lys504Glu
NP_000518.1:p.Lys504Glu
NP_001182727.1:p.Lys504Glu
NP_001182728.1:p.Lys463Glu
NP_001182729.1:p.Lys336Glu
NP_001182732.1:p.Lys377Glu
LRG_274t1:c.1510A>G
LRG_274:g.29306A>G
NC_000019.9:g.11224362A>G
NM_000527.4(LDLR):c.1510A>G
NM_000527.4:c.1510A>G
c.1510A>G

Protein change:

K336E

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001446; dbSNP: rs730882103

NCBI 1000 Genomes Browser:

rs730882103

Molecular consequence:

NM_000527.5:c.1510A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1510A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1387A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1006A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1129A>G - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

no known functional consequence - Comment(s)

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005040352	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Mar 13, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19318025, 27784735, 25647241, 33508743, 34297352 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005040352

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Mar 13, 2024)

germline

clinical testing

PubMed (5)
[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

Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform.

Alonso R, Defesche JC, Tejedor D, Castillo S, Stef M, Mata N, Gomez-Enterria P, Martinez-Faedo C, Forga L, Mata P.

Clin Biochem. 2009 Jun;42(9):899-903. doi: 10.1016/j.clinbiochem.2009.01.017. Epub 2009 Feb 6.

PubMed [citation]

PMID:: 19318025

Homozygous Familial Hypercholesterolemia in Spain: Prevalence and Phenotype-Genotype Relationship.

Sánchez-Hernández RM, Civeira F, Stef M, Perez-Calahorra S, Almagro F, Plana N, Novoa FJ, Sáenz-Aranzubía P, Mosquera D, Soler C, Fuentes FJ, Brito-Casillas Y, Real JT, Blanco-Vaca F, Ascaso JF, Pocovi M.

Circ Cardiovasc Genet. 2016 Dec;9(6):504-510. doi: 10.1161/CIRCGENETICS.116.001545. Epub 2016 Oct 26.

PubMed [citation]

PMID:: 27784735

See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005040352.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Variant summary: LDLR c.1510A>G (p.Lys504Glu) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251454 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1510A>G has been reported in the literature in individuals affected with Familial Hypercholesterolemia without strong evidence of causality (e.g. Alonso_2009, Sanchez-Hernandez_2016, Di Taranto_2021, Futema_2021). These reports do not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. At least one publication reports experimental evidence evaluating an impact on protein function (Thormaehlen_2015). These results showed no damaging effect of this variant. The following publications have been ascertained in the context of this evaluation (PMID: 19318025, 25647241, 27784735, 34297352, 33508743). ClinVar contains an entry for this variant (Variation ID: 183117). Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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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