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NM_000527.5(LDLR):c.-121T>C AND LDLR-related disorder

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 14, 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:
RCV003401126.4

Allele description [Variation Report for NM_000527.5(LDLR):c.-121T>C]

NM_000527.5(LDLR):c.-121T>C

Genes:
LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
LDLR-AS1:LDLR antisense RNA 1 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_000527.5(LDLR):c.-121T>C
HGVS:
  • NC_000019.10:g.11089428T>C
  • NG_009060.1:g.5048T>C
  • NM_000527.5:c.-121T>CMANE SELECT
  • LRG_274t1:c.-121T>C
  • LRG_274:g.5048T>C
  • NC_000019.9:g.11200104T>C
  • NM_000527.4:c.-121T>C
  • NR_163945.1:n.232A>G
  • c.-121T>C
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000002; dbSNP: rs777716188
NCBI 1000 Genomes Browser:
rs777716188
Molecular consequence:
  • NR_163945.1:n.232A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000527.5:c.-121T>C - upstream transcript variant - [Sequence Ontology: SO:0001986]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004119849PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Mar 14, 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, SCV004119849.1

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

Description

The LDLR c.-121T>C variant is located in the 5' untranslated region. This variant has been reported in multiple individuals with Hypercholesterolemia (Taylor et al. 2010. PubMed ID: 20236128; Hooper et al. 2012. PubMed ID: 22883975; Faiz et al. 2013. PubMed ID: 24075752; Trinder et al. 2019. PubMed ID: 31345425. Table S3). Functional study showed that this variant decreases LDLR gene expression (Khamis et al. 2014. PubMed ID: 25248394). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. In ClinVar, this variant has conflicting interpretations of likely pathogenic and uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/). This variant is interpreted as likely pathogenic.

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

Last Updated: Sep 29, 2024