NM_000527.5(LDLR):c.1586+5G>C AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 18, 2024
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:: RCV004023446.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1586+5G>C]

NM_000527.5(LDLR):c.1586+5G>C

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.1586+5G>C

HGVS:

NC_000019.10:g.11113767G>C
NG_009060.1:g.29387G>C
NM_000527.5:c.1586+5G>CMANE SELECT
NM_001195798.2:c.1586+5G>C
NM_001195799.2:c.1463+5G>C
NM_001195800.2:c.1082+5G>C
NM_001195803.2:c.1205+5G>C
LRG_274t1:c.1586+5G>C
LRG_274:g.29387G>C
NC_000019.9:g.11224443G>C
NC_000019.9:g.11224443G>C
NM_000527.4(LDLR):c.1586+5G>C
NM_000527.4:c.1586+5G>C

Links:

dbSNP: rs781362878

NCBI 1000 Genomes Browser:

rs781362878

Molecular consequence:

NM_000527.5:c.1586+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001195798.2:c.1586+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001195799.2:c.1463+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001195800.2:c.1082+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.1205+5G>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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D005222 (1)
MeSH
Mental Fatigue
Mental Fatigue
A condition of low alertness or cognitive impairment, usually associated with prolonged mental activities or stress.<br/>Year introduced: 1995

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003984201	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 18, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17964958, 23680767, 34037665 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003984201

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 18, 2024)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

LDLR and ApoB are major genetic causes of autosomal dominant hypercholesterolemia in a Taiwanese population.

Yang KC, Su YN, Shew JY, Yang KY, Tseng WK, Wu CC, Lee YT.

J Formos Med Assoc. 2007 Oct;106(10):799-807.

PubMed [citation]

PMID:: 17964958

The use of next-generation sequencing in clinical diagnosis of familial hypercholesterolemia.

Vandrovcova J, Thomas ER, Atanur SS, Norsworthy PJ, Neuwirth C, Tan Y, Kasperaviciute D, Biggs J, Game L, Mueller M, Soutar AK, Aitman TJ.

Genet Med. 2013 Dec;15(12):948-57. doi: 10.1038/gim.2013.55. Epub 2013 May 16.

PubMed [citation]

PMID:: 23680767

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV003984201.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.1586+5G>C intronic variant results from a G to C substitution 5 nucleotides after coding exon 10 in the LDLR gene. This variant has been reported in familial hypercholesterolemia (FH) cohorts (Yang KC et al. J Formos Med Assoc, 2007 Oct;106:799-807; Vandrovcova J et al. Genet Med, 2013 Dec;15:948-57; Sturm AC et al. JAMA Cardiol, 2021 Aug;6:902-909). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site. Based on the available evidence, the clinical significance of this variant remains unclear.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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