NM_000527.5(LDLR):c.1435C>G (p.Leu479Val) AND Hypercholesterolemia, familial, 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 23, 2024
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:: RCV000508973.11

Allele description [Variation Report for NM_000527.5(LDLR):c.1435C>G (p.Leu479Val)]

NM_000527.5(LDLR):c.1435C>G (p.Leu479Val)

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.1435C>G (p.Leu479Val)

Other names:

NM_000527.5(LDLR):c.1435C>G; p.Leu479Val

HGVS:

NC_000019.10:g.11113611C>G
NG_009060.1:g.29231C>G
NM_000527.5:c.1435C>GMANE SELECT
NM_001195798.2:c.1435C>G
NM_001195799.2:c.1312C>G
NM_001195800.2:c.931C>G
NM_001195803.2:c.1054C>G
NP_000518.1:p.Leu479Val
NP_000518.1:p.Leu479Val
NP_001182727.1:p.Leu479Val
NP_001182728.1:p.Leu438Val
NP_001182729.1:p.Leu311Val
NP_001182732.1:p.Leu352Val
LRG_274t1:c.1435C>G
LRG_274:g.29231C>G
LRG_274p1:p.Leu479Val
NC_000019.9:g.11224287C>G
NM_000527.4:c.1435C>G

Protein change:

L311V

Links:

dbSNP: rs1254928151

NCBI 1000 Genomes Browser:

rs1254928151

Molecular consequence:

NM_000527.5:c.1435C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1435C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1312C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.931C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1054C>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
SCV000606426	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	no assertion criteria provided	Pathogenic	germline	research
SCV005903144	ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel	reviewed by expert panel (ClinGen FH ACMG Specifications v1-2)	Uncertain Significance (Feb 23, 2024)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000606426

Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum

no assertion criteria provided

Pathogenic

germline

research

SCV005903144

ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel

reviewed by expert panel

(ClinGen FH ACMG Specifications v1-2)

Uncertain Significance
(Feb 23, 2024)

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, SCV000606426.1

#	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, SCV005903144.1

#	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.1435C>G (p.Leu479Val) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence code PM2 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 23 February 2024. The supporting evidence is as follows: PM2: PopMax MAF = 0.00008 (0.008%) in African exomes (gnomAD v4.0.0).

#	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: Apr 7, 2025

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