NM_000527.5(LDLR):c.300C>G (p.Asp100Glu) AND Hypercholesterolemia, familial, 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 28, 2023
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:: RCV000508944.2

Allele description [Variation Report for NM_000527.5(LDLR):c.300C>G (p.Asp100Glu)]

NM_000527.5(LDLR):c.300C>G (p.Asp100Glu)

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.300C>G (p.Asp100Glu)

Other names:

NM_000527.5(LDLR):c.300C>G; p.Asp100Glu

HGVS:

NC_000019.10:g.11102773C>G
NG_009060.1:g.18393C>G
NM_000527.5:c.300C>GMANE SELECT
NM_001195798.2:c.300C>G
NM_001195799.2:c.190+2428C>G
NM_001195800.2:c.300C>G
NM_001195803.2:c.300C>G
NP_000518.1:p.Asp100Glu
NP_000518.1:p.Asp100Glu
NP_001182727.1:p.Asp100Glu
NP_001182729.1:p.Asp100Glu
NP_001182732.1:p.Asp100Glu
LRG_274t1:c.300C>G
LRG_274:g.18393C>G
LRG_274p1:p.Asp100Glu
NC_000019.9:g.11213449C>G
NM_000527.4:c.300C>G

Protein change:

D100E

Links:

dbSNP: rs766709484

NCBI 1000 Genomes Browser:

rs766709484

Molecular consequence:

NM_001195799.2:c.190+2428C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.300C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.300C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.300C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.300C>G - missense variant - [Sequence Ontology: SO:0001583]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000606068	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	no assertion criteria provided	Pathogenic	germline	research
SCV004022468	ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel	reviewed by expert panel (ClinGen FH ACMG Specifications v1-2)	Uncertain significance (Apr 28, 2023)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000606068

Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum

no assertion criteria provided

Pathogenic

germline

research

SCV004022468

ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel

reviewed by expert panel

(ClinGen FH ACMG Specifications v1-2)

Uncertain significance
(Apr 28, 2023)

germline

curation

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	research, curation

Details of each submission

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum, SCV000606068.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	not provided

#	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

From ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel, SCV004022468.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

The NM_000527.5(LDLR):c.300C>G (p.Asp100Glu) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2, PP4, PS4_supporting 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 from gnomAD (gnomAD v2.1.1). PS4_supporting - Variant meets PM2 and is identified in 2 unrelated index cases who fulfill SB possible for FH from PMID 26361156. PP4 - Variant meets PM2 and is identified in 2 unrelated index cases who fulfill clinical criteria for FH from PMID 26361156, after alternative causes for high cholesterol were excluded

#	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: Aug 13, 2023

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