U.S. flag

An official website of the United States government

NM_000527.5(LDLR):c.428G>A (p.Cys143Tyr) AND LDLR-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 31, 2023
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:
RCV003401202.4

Allele description [Variation Report for NM_000527.5(LDLR):c.428G>A (p.Cys143Tyr)]

NM_000527.5(LDLR):c.428G>A (p.Cys143Tyr)

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.428G>A (p.Cys143Tyr)
HGVS:
  • NC_000019.10:g.11105334G>A
  • NG_009060.1:g.20954G>A
  • NM_000527.5:c.428G>AMANE SELECT
  • NM_001195798.2:c.428G>A
  • NM_001195799.2:c.305G>A
  • NM_001195800.2:c.314-2058G>A
  • NM_001195803.2:c.314-1231G>A
  • NP_000518.1:p.Cys143Tyr
  • NP_000518.1:p.Cys143Tyr
  • NP_001182727.1:p.Cys143Tyr
  • NP_001182728.1:p.Cys102Tyr
  • LRG_274t1:c.428G>A
  • LRG_274:g.20954G>A
  • LRG_274p1:p.Cys143Tyr
  • NC_000019.9:g.11216010G>A
  • NM_000527.4:c.428G>A
  • c.428G>A
Protein change:
C102Y
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000059; dbSNP: rs879254522
NCBI 1000 Genomes Browser:
rs879254522
Molecular consequence:
  • NM_001195800.2:c.314-2058G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195803.2:c.314-1231G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.428G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.428G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.305G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
LDLR-related disorder
Synonyms:
LDLR-related condition
Identifiers:

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004103089PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Aug 31, 2023) 		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 PreventionGenetics, part of Exact Sciences, SCV004103089.1

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

Description

The LDLR c.428G>A variant is predicted to result in the amino acid substitution p.Cys143Tyr. This variant also described using legacy nomenclature as p.Cys122Tyr, has been documented in several reports as a causative variant for Hypercholesterolemia (Genschel et al. 2001. PubMed ID: 11295843; Cao et al. 2003. PubMed ID: 14570618; Dedoussis et al. 2004. PubMed ID: 14974088; Wang et al. 2008. PubMed ID: 19073363; Kim et al. 2018. PubMed ID: 29399563). Functional study showed that this variant results in defective LDLR binding ability (Wang et al. 2008. PubMed ID: 19073363). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. In ClinVar, this variant is interpreted as pathogenic or likely pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/251220/). This variant is interpreted as pathogenic.

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

Last Updated: Sep 29, 2024