U.S. flag

An official website of the United States government

NM_000527.5(LDLR):c.1186+1G>T AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 27, 2022
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:
RCV002336345.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1186+1G>T]

NM_000527.5(LDLR):c.1186+1G>T

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.1186+1G>T
HGVS:
  • NC_000019.10:g.11111640G>T
  • NG_009060.1:g.27260G>T
  • NM_000527.5:c.1186+1G>TMANE SELECT
  • NM_001195798.2:c.1186+1G>T
  • NM_001195799.2:c.1063+1G>T
  • NM_001195800.2:c.682+1G>T
  • NM_001195803.2:c.805+1G>T
  • LRG_274t1:c.1186+1G>T
  • LRG_274:g.27260G>T
  • NC_000019.9:g.11222316G>T
  • NM_000527.4:c.1186+1G>T
Links:
dbSNP: rs730880131
NCBI 1000 Genomes Browser:
rs730880131
Molecular consequence:
  • NM_000527.5:c.1186+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195798.2:c.1186+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195799.2:c.1063+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195800.2:c.682+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001195803.2:c.805+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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
SCV002638012Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jul 27, 2022) 		germlineclinical testing

PubMed (4)
[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

A novel splice site mutation of the LDL receptor gene in a Tunisian hypercholesterolemic family.

Jelassi A, Najah M, Jguirim I, Maatouk F, Lestavel S, Laroussi OS, Rouis M, Boileau C, Rabès JP, Varret M, Slimane MN.

Clin Chim Acta. 2008 Jun;392(1-2):25-9. doi: 10.1016/j.cca.2008.02.019. Epub 2008 Mar 4.

PubMed [citation]
PMID:
18355452

Moderate phenotypic expression of familial hypercholesterolemia in Tunisia.

Jelassi A, Slimani A, Jguirim I, Najah M, Abid A, Boughamoura L, Mzid J, Fkih M, Maatouk F, Rouis M, Varret M, Slimane MN.

Clin Chim Acta. 2010 May 2;411(9-10):735-8. doi: 10.1016/j.cca.2010.02.008. Epub 2010 Feb 6.

PubMed [citation]
PMID:
20144596
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002638012.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The c.1186+1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide after coding exon 8 of the LDLR gene. This variant has been detected in individuals with hypercholesterolemia and individuals from familial hypercholesterolemia cohorts (Miroshnikova VV et al. Biomed Rep. 2021 Jan;14(1):15; Meshkov A et al. Genes (Basel). 2021 01;12(1); Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. In addition to the clinical data presented in the literature, 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. As such, this alteration is classified as a disease-causing mutation.

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

Last Updated: May 7, 2024