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NM_000527.5(LDLR):c.482T>A (p.Ile161Asn) AND Hypercholesterolemia, familial, 1

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 11, 2020
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:
RCV001537876.1

Allele description [Variation Report for NM_000527.5(LDLR):c.482T>A (p.Ile161Asn)]

NM_000527.5(LDLR):c.482T>A (p.Ile161Asn)

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.482T>A (p.Ile161Asn)
HGVS:
  • NC_000019.10:g.11105388T>A
  • NG_009060.1:g.21008T>A
  • NM_000527.5:c.482T>AMANE SELECT
  • NM_001195798.2:c.482T>A
  • NM_001195799.2:c.359T>A
  • NM_001195800.2:c.314-2004T>A
  • NM_001195803.2:c.314-1177T>A
  • NP_000518.1:p.Ile161Asn
  • NP_001182727.1:p.Ile161Asn
  • NP_001182728.1:p.Ile120Asn
  • LRG_274t1:c.482T>A
  • LRG_274:g.21008T>A
  • NC_000019.9:g.11216064T>A
  • NM_000527.4:c.482T>A
Protein change:
I120N
Links:
dbSNP: rs754933794
NCBI 1000 Genomes Browser:
rs754933794
Molecular consequence:
  • NM_001195800.2:c.314-2004T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195803.2:c.314-1177T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.482T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.482T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.359T>A - 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

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001754779Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jun 11, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV001754779.1

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

Description

The c.482T>A (p.Ile161Asn) variant is located in exon 4 that encodes a well-established ligand (LDL) binding domain critical for function (PMID: 2600087). This variant is observed at very low frequency in the gnomAD population database (1/251256 alleles) and is predicted to be deleterious by multiple bioinformatics algorithms. It was identified in an individual with a clinical diagnosis of FH. Another missense variant at the same residue, p.Ile161Thr, has been previously reported in an individual with FH (PMID: 26298359). Therefore, the c.482T>A (p.Ile161Asn) variant in the LDLR gene is classified as likely pathogenic.

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

Last Updated: Feb 20, 2024