NM_000527.5(LDLR):c.1586+1G>A AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: May 24, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000238067.6

Allele description [Variation Report for NM_000527.5(LDLR):c.1586+1G>A]

NM_000527.5(LDLR):c.1586+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.1586+1G>A

Other names:

FH Agrigento

HGVS:

NC_000019.10:g.11113763G>A
NG_009060.1:g.29383G>A
NM_000527.5:c.1586+1G>AMANE SELECT
NM_001195798.2:c.1586+1G>A
NM_001195799.2:c.1463+1G>A
NM_001195800.2:c.1082+1G>A
NM_001195803.2:c.1205+1G>A
LRG_274t1:c.1586+1G>A
LRG_274:g.29383G>A
NC_000019.9:g.11224439G>A
NM_000527.4:c.1586+1G>A
c.1586+1G>A
p.(Thr454_Gly529del)andp.(Gly529_Phe530ins22)

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001460;

Molecular consequence:

NM_000527.5:c.1586+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001195798.2:c.1586+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001195799.2:c.1463+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001195800.2:c.1082+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001195803.2:c.1205+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Observations:

Condition(s)

Name:: Hypercholesterolemia, familial, 1
Synonyms:: LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007750; MedGen: C0745103; Orphanet: 391665; OMIM: 143890

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000295508	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Pathogenic (Mar 25, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000503369	Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 16, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000588593	Laboratory of Genetics and Molecular Cardiology, University of São Paulo - HipercolBrasil	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2016)	germline	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 9974426
SCV000606458	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	no assertion criteria provided	Pathogenic	germline	research
SCV001653642	Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 24, 2021)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 9974426, 25487149, 25525159, 30710474, 31491741, 32977124, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	4	not provided	not provided	2601	not provided	clinical testing, literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	research
Caucasian	germline	yes	29	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Analysis of LDL receptor gene mutations in Italian patients with homozygous familial hypercholesterolemia.

Bertolini S, Cassanelli S, Garuti R, Ghisellini M, Simone ML, Rolleri M, Masturzo P, Calandra S.

Arterioscler Thromb Vasc Biol. 1999 Feb;19(2):408-18.

PubMed [citation]

PMID:: 9974426

Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction.

Do R, Stitziel NO, Won HH, Jørgensen AB, Duga S, Angelica Merlini P, Kiezun A, Farrall M, Goel A, Zuk O, Guella I, Asselta R, Lange LA, Peloso GM, Auer PL; NHLBI Exome Sequencing Project., Girelli D, Martinelli N, Farlow DN, DePristo MA, Roberts R, Stewart AF, et al.

Nature. 2015 Feb 5;518(7537):102-6. doi: 10.1038/nature13917. Epub 2014 Dec 10.

PubMed [citation]

PMID:: 25487149
PMCID:: PMC4319990

See all PubMed Citations (7)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295508.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	literature only	PubMed (1)

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

From Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix, SCV000503369.1

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

Description

subjects mutated among 2600 FH index cases screened = 3

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	2600	not provided	not provided		3	not provided	not provided	not provided

From Laboratory of Genetics and Molecular Cardiology, University of São Paulo - HipercolBrasil, SCV000588593.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (2)
2	not provided	not provided	not provided	not provided	research	PubMed (2)

Description

%MAF(ExAC):0.0008425

"Assay description:Hmz patient fibroblast, 125I-LDL and RNA assays"

PubMed [ID: 9974426]

#	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
2	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum, SCV000606458.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	not provided

#	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

From Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II, SCV001653642.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasian	29	not provided	not provided	clinical testing	PubMed (7)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		29	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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