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NM_000527.5(LDLR):c.314-1G>A AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 24, 2021
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:
RCV002321914.2

Allele description [Variation Report for NM_000527.5(LDLR):c.314-1G>A]

NM_000527.5(LDLR):c.314-1G>A

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.314-1G>A
HGVS:
  • NC_000019.10:g.11105219G>A
  • NG_009060.1:g.20839G>A
  • NG_140410.1:g.436G>A
  • NM_000527.5:c.314-1G>AMANE SELECT
  • NM_001195798.2:c.314-1G>A
  • NM_001195799.2:c.191-1G>A
  • NM_001195800.2:c.314-2173G>A
  • NM_001195803.2:c.314-1346G>A
  • LRG_274t1:c.314-1G>A
  • LRG_274:g.20839G>A
  • NC_000019.9:g.11215895G>A
  • NM_000527.4:c.314-1G>A
  • c.314-1G>A
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001697; dbSNP: rs879254471
NCBI 1000 Genomes Browser:
rs879254471
Molecular consequence:
  • NM_001195800.2:c.314-2173G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195803.2:c.314-1346G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.314-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001195798.2:c.314-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001195799.2:c.191-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV002610619Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(May 24, 2021) 		germlineclinical testing

PubMed (6)
[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

The molecular basis of familial hypercholesterolemia in The Netherlands.

Fouchier SW, Defesche JC, Umans-Eckenhausen MW, Kastelein JP.

Hum Genet. 2001 Dec;109(6):602-15. Epub 2001 Nov 9.

PubMed [citation]
PMID:
11810272

Effects of intronic mutations in the LDLR gene on pre-mRNA splicing: Comparison of wet-lab and bioinformatics analyses.

Holla ØL, Nakken S, Mattingsdal M, Ranheim T, Berge KE, Defesche JC, Leren TP.

Mol Genet Metab. 2009 Apr;96(4):245-52. doi: 10.1016/j.ymgme.2008.12.014. Epub 2009 Feb 10.

PubMed [citation]
PMID:
19208450
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002610619.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

The c.314-1G>A pathogenic mutation, results from a G to A one nucleotide upstream from coding exon 4 of the LDLR gene. This alteration has been reported in familial hypercholestremia (FH) patients (Huijgen et al 2010; Hum Mut 31(6):752-60; Lombardi P et al. Hum Mutat, 1998;Suppl 1:S172-4; Luirink IK et al. Atherosclerosis, 2019 06;285:87-92). This alteration has also been shown to have an impact on protein function (Holla ØL et al. Mol Genet Metab, 2009 Apr;96:245-52). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. Based on the supporting evidence, 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