U.S. flag

An official website of the United States government

NM_000527.5(LDLR):c.1800G>T (p.Glu600Asp) AND Hypercholesterolemia, familial, 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 11, 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:
RCV004008163.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1800G>T (p.Glu600Asp)]

NM_000527.5(LDLR):c.1800G>T (p.Glu600Asp)

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.1800G>T (p.Glu600Asp)
HGVS:
  • NC_000019.10:g.11116953G>T
  • NG_009060.1:g.32573G>T
  • NM_000527.5:c.1800G>TMANE SELECT
  • NM_001195798.2:c.1800G>T
  • NM_001195799.2:c.1677G>T
  • NM_001195800.2:c.1296G>T
  • NM_001195803.2:c.1419G>T
  • NP_000518.1:p.Glu600Asp
  • NP_000518.1:p.Glu600Asp
  • NP_001182727.1:p.Glu600Asp
  • NP_001182728.1:p.Glu559Asp
  • NP_001182729.1:p.Glu432Asp
  • NP_001182732.1:p.Glu473Asp
  • LRG_274t1:c.1800G>T
  • LRG_274:g.32573G>T
  • LRG_274p1:p.Glu600Asp
  • NC_000019.9:g.11227629G>T
  • NM_000527.4:c.1800G>T
Protein change:
E432D
Molecular consequence:
  • NM_000527.5:c.1800G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1800G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1677G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1296G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1419G>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Name:
Hypercholesterolemia, familial, 1
Synonyms:
LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007750; MedGen: C0745103; Orphanet: 391665; OMIM: 143890

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004815834All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Jan 11, 2024) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown2not providednot provided108544not providedclinical testing

Citations

PubMed

Femoral atherosclerosis in heterozygous familial hypercholesterolemia: influence of the genetic defect.

Junyent M, Gilabert R, Zambón D, Pocoví M, Mallén M, Cofán M, Núñez I, Civeira F, Tejedor D, Ros E.

Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):580-6. Epub 2007 Dec 20.

PubMed [citation]
PMID:
18096825

Efficacy of alirocumab in 1191 patients with a wide spectrum of mutations in genes causative for familial hypercholesterolemia.

Defesche JC, Stefanutti C, Langslet G, Hopkins PN, Seiz W, Baccara-Dinet MT, Hamon SC, Banerjee P, Kastelein JJP.

J Clin Lipidol. 2017 Nov - Dec;11(6):1338-1346.e7. doi: 10.1016/j.jacl.2017.08.016. Epub 2017 Sep 4. Erratum in: J Clin Lipidol. 2020 Sep - Oct;14(5):742. doi: 10.1016/j.jacl.2020.09.010.

PubMed [citation]
PMID:
28964736
See all PubMed Citations (3)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004815834.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (3)

Description

This missense variant (also known as p.Glu579Asp in the mature protein) replaces glutamic acid with aspartic acid at codon 600 of the LDLR protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with LDLR-related conditions in the literature. A different variant causing the same amino acid change, c.1800G>C, has been identified in 2 individuals affected with familial hypercholesterolemia (PMID: 18096825, 28964736). This variant has been identified in 1/251488 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided2not providednot providednot provided

Last Updated: May 7, 2024