NM_000527.5(LDLR):c.1575T>G (p.Asp525Glu) AND Familial hypercholesterolemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 15, 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:: RCV001179615.4

Allele description [Variation Report for NM_000527.5(LDLR):c.1575T>G (p.Asp525Glu)]

NM_000527.5(LDLR):c.1575T>G (p.Asp525Glu)

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.1575T>G (p.Asp525Glu)

HGVS:

NC_000019.10:g.11113751T>G
NG_009060.1:g.29371T>G
NM_000527.5:c.1575T>GMANE SELECT
NM_001195798.2:c.1575T>G
NM_001195799.2:c.1452T>G
NM_001195800.2:c.1071T>G
NM_001195803.2:c.1194T>G
NP_000518.1:p.Asp525Glu
NP_001182727.1:p.Asp525Glu
NP_001182728.1:p.Asp484Glu
NP_001182729.1:p.Asp357Glu
NP_001182732.1:p.Asp398Glu
LRG_274t1:c.1575T>G
LRG_274:g.29371T>G
NC_000019.9:g.11224427T>G
NC_000019.9:g.11224427T>G
NM_000527.4:c.1575T>G

Protein change:

D357E

Links:

dbSNP: rs763884010

NCBI 1000 Genomes Browser:

rs763884010

Molecular consequence:

NM_000527.5:c.1575T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1575T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1452T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1071T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1194T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001344323	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 15, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32041611, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001344323

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 15, 2023)

germline

clinical testing

PubMed (2)
[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

Six years' experience with LipidSeq: clinical and research learnings from a hybrid, targeted sequencing panel for dyslipidemias.

Dron JS, Wang J, McIntyre AD, Iacocca MA, Robinson JF, Ban MR, Cao H, Hegele RA.

BMC Med Genomics. 2020 Feb 10;13(1):23. doi: 10.1186/s12920-020-0669-2.

PubMed [citation]

PMID:: 32041611
PMCID:: PMC7011550

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001344323.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This missense variant (also known as p.Asp504Glu in the mature protein) replaces aspartic acid with glutamic acid at codon 525 of the LDLR protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dyslipidemia (PMID: 32041611). This variant has been identified in 2/282622 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of 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 1, 2024

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