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NM_000527.5(LDLR):c.1158C>G (p.Asp386Glu) AND Hypercholesterolemia, familial, 1

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
Mar 25, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV000238278.6

Allele description [Variation Report for NM_000527.5(LDLR):c.1158C>G (p.Asp386Glu)]

NM_000527.5(LDLR):c.1158C>G (p.Asp386Glu)

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.1158C>G (p.Asp386Glu)
Other names:
FH Cyprus-2; NM_000527.5(LDLR):c.1158C>G
HGVS:
  • NC_000019.10:g.11111611C>G
  • NG_009060.1:g.27231C>G
  • NM_000527.5:c.1158C>GMANE SELECT
  • NM_001195798.2:c.1158C>G
  • NM_001195799.2:c.1035C>G
  • NM_001195800.2:c.654C>G
  • NM_001195803.2:c.777C>G
  • NP_000518.1:p.Asp386Glu
  • NP_000518.1:p.Asp386Glu
  • NP_001182727.1:p.Asp386Glu
  • NP_001182728.1:p.Asp345Glu
  • NP_001182729.1:p.Asp218Glu
  • NP_001182732.1:p.Asp259Glu
  • LRG_274t1:c.1158C>G
  • LRG_274:g.27231C>G
  • LRG_274p1:p.Asp386Glu
  • NC_000019.9:g.11222287C>G
  • NM_000527.4:c.1158C>G
  • c.1158C>G
Protein change:
D218E
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000441; dbSNP: rs879254810
NCBI 1000 Genomes Browser:
rs879254810
Molecular consequence:
  • NM_000527.5:c.1158C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1158C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1035C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.654C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.777C>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
4

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000295250LDLR-LOVD, British Heart Foundation
criteria provided, single submitter

(ACGS Guidelines, 2013)		Likely benign
(Mar 25, 2016) 		germlineliterature only

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

Citation Link,

SCV000503306Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Dec 16, 2016) 		germlineclinical testing

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

SCV002506405ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel
reviewed by expert panel

(ClinGen FH ACMG Specifications v1-2)		Uncertain significance
(Mar 25, 2022) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes4not providednot provided2603not providedclinical testing, literature only
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Molecular characterization of familial hypercholesterolemia in German and Greek patients.

Dedoussis GV, Genschel J, Bochow B, Pitsavos C, Skoumas J, Prassa M, Lkhagvasuren S, Toutouzas P, Vogt A, Kassner U, Thomas HP, Schmidt H.

Hum Mutat. 2004 Mar;23(3):285-6.

PubMed [citation]
PMID:
14974088

Mutational analysis in UK patients with a clinical diagnosis of familial hypercholesterolaemia: relationship with plasma lipid traits, heart disease risk and utility in relative tracing.

Humphries SE, Cranston T, Allen M, Middleton-Price H, Fernandez MC, Senior V, Hawe E, Iversen A, Wray R, Crook MA, Wierzbicki AS.

J Mol Med (Berl). 2006 Mar;84(3):203-14. Epub 2005 Dec 31.

PubMed [citation]
PMID:
16389549
See all PubMed Citations (4)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295250.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedliterature only PubMed (3)
2not provided1not providednot providedliterature only PubMed (3)
3not provided1not providednot providedliterature only PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided
2germlineyes1not providednot provided1not providednot providednot provided
3germlineyes1not providednot provided1not providednot providednot provided

From Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix, SCV000503306.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

subject mutated among 2600 FH index cases screened = 1 compound heterozygous with LDLCmax = 300 mg/dL / Software predictions: Damaging

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes2600not providednot provided1not providednot providednot provided

From ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel, SCV002506405.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000527.5 (LDLR):c.1158C>G (p.Asp386Glu) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2, PP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM2: This variant is absent in gnomAD (gnomAD v2.1.1). PP4: This variant meets PM2 and is identified in 1 index case who met clinical criteria for FH after alternative causes for high cholesterol were excluded (Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024