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NM_000527.5(LDLR):c.564C>A (p.Tyr188Ter) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 13, 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:
RCV002347938.2

Allele description [Variation Report for NM_000527.5(LDLR):c.564C>A (p.Tyr188Ter)]

NM_000527.5(LDLR):c.564C>A (p.Tyr188Ter)

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.564C>A (p.Tyr188Ter)
HGVS:
  • NC_000019.10:g.11105470C>A
  • NG_009060.1:g.21090C>A
  • NM_000527.5:c.564C>AMANE SELECT
  • NM_001195798.2:c.564C>A
  • NM_001195799.2:c.441C>A
  • NM_001195800.2:c.314-1922C>A
  • NM_001195803.2:c.314-1095C>A
  • NP_000518.1:p.Tyr188Ter
  • NP_000518.1:p.Tyr188Ter
  • NP_001182727.1:p.Tyr188Ter
  • NP_001182728.1:p.Tyr147Ter
  • LRG_274t1:c.564C>A
  • LRG_274:g.21090C>A
  • LRG_274p1:p.Tyr188Ter
  • NC_000019.9:g.11216146C>A
  • NM_000527.4:c.564C>A
  • c.564C>A
Protein change:
Y147*
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000704; dbSNP: rs121908034
NCBI 1000 Genomes Browser:
rs121908034
Molecular consequence:
  • NM_001195800.2:c.314-1922C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195803.2:c.314-1095C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.564C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001195798.2:c.564C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001195799.2:c.441C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002652949Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Feb 13, 2020) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F).

Ekström U, Abrahamson M, Florén CH, Tollig H, Wettrell G, Nilsson G, Sun XM, Soutar AK, Nilsson-Ehle P.

Clin Genet. 1999 May;55(5):332-9.

PubMed [citation]
PMID:
10422803

A nonsense mutation in the LDL receptor gene leads to familial hypercholesterolemia in the Druze sect.

Landsberger D, Meiner V, Reshef A, Levy Y, van der Westhuyzen DR, Coetzee GA, Leitersdorf E.

Am J Hum Genet. 1992 Feb;50(2):427-33.

PubMed [citation]
PMID:
1734722
PMCID:
PMC1682466
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002652949.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The p.Y188* variant (also known as c.564C>A and p.Y167X), located in coding exon 4 of the LDLR gene, results from a C to A substitution at nucleotide position 564. This changes the amino acid from a tyrosine to a stop codon within coding exon 4. This variant has been reported in multiple individuals with a personal and family history of hypercholesterolemia, both as a heterozygous and homozygous variant (Taylor A et al. Clin. Genet., 2007 Jun;71:561-8, Landsberger D et al. Am. J. Hum. Genet., 1992 Feb;50:427-33, Ekström U et al. Clin. Genet., 1999 May;55:332-9). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024