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NM_000527.5(LDLR):c.1439C>T (p.Ala480Val) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 21, 2017
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:
RCV000485078.1

Allele description [Variation Report for NM_000527.5(LDLR):c.1439C>T (p.Ala480Val)]

NM_000527.5(LDLR):c.1439C>T (p.Ala480Val)

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.1439C>T (p.Ala480Val)
HGVS:
  • NC_000019.10:g.11113615C>T
  • NG_009060.1:g.29235C>T
  • NM_000527.5:c.1439C>TMANE SELECT
  • NM_001195798.2:c.1439C>T
  • NM_001195799.2:c.1316C>T
  • NM_001195800.2:c.935C>T
  • NM_001195803.2:c.1058C>T
  • NP_000518.1:p.Ala480Val
  • NP_000518.1:p.Ala480Val
  • NP_001182727.1:p.Ala480Val
  • NP_001182728.1:p.Ala439Val
  • NP_001182729.1:p.Ala312Val
  • NP_001182732.1:p.Ala353Val
  • LRG_274t1:c.1439C>T
  • LRG_274:g.29235C>T
  • LRG_274p1:p.Ala480Val
  • NC_000019.9:g.11224291C>T
  • NM_000527.4:c.1439C>T
Protein change:
A312V
Links:
dbSNP: rs1064794259
NCBI 1000 Genomes Browser:
rs1064794259
Molecular consequence:
  • NM_000527.5:c.1439C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1439C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1316C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.935C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1058C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000568523GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Pathogenic
(Feb 21, 2017) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000568523.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The A480V pathogenic variant in the LDLR gene has been reported in the homozygous state in a Chinese male with disease manifestation at less than 10 years of age. The A480V variant segregated with disease in at least three heterozygous family members, all of whom demonstrated a milder phenotype (Lin et. al., 2008). The A480V variant has also been reported in two other patients with clinical signs of FH, including one proband with severe hypercholesterolemia at young age who was compound heterozygous for a W577G variant (Brusgaard et al., 2006; Jiang et al., 2016). The A480V variant resides within the LDL-receptor class B 2 repeat and results in a conservative amino acid substitution at a position that is highly conserved across species. In addition, functional analysis of homozygous LDLR expression demonstrated that, compared to normal controls, A480V LDLR expression, binding ability, and up-taking ability was 39%, 63%, and 76% respectively; heterozygous function was also shown to be impaired to a lesser degree (Lin et al., 2008). Finally, the A480V variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).

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

Last Updated: Sep 29, 2024