NM_000527.5(LDLR):c.313_313+1del AND Homozygous familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 11, 2019
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:: RCV004017501.1

Allele description [Variation Report for NM_000527.5(LDLR):c.313_313+1del]

NM_000527.5(LDLR):c.313_313+1del

Gene:

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.313_313+1del

Other names:

FH Lille

HGVS:

NC_000019.10:g.11102786_11102787del
NG_009060.1:g.18406_18407del
NM_000527.4(LDLR):c.313_313+1delCG
NM_000527.5:c.313_313+1delMANE SELECT
NM_001195798.2:c.313_313+1del
NM_001195799.2:c.191-2434_191-2433del
NM_001195800.2:c.313_313+1del
NM_001195803.2:c.313_313+1del
LRG_274t1:c.313_313+1del
LRG_274:g.18406_18407del
NC_000019.10:g.11102786_11102787delCG
NC_000019.9:g.11213462_11213463del
NM_000527.4(LDLR):c.313_313+1delCG
NM_000527.4:c.313_313+1del
NM_000527.4:c.313_313+1delCG
NM_000527.5:c.313_313+1del
c.313_313+1del
p.Lys107Argfs*99

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001692; dbSNP: rs875989896

NCBI 1000 Genomes Browser:

rs875989896

Molecular consequence:

NM_001195799.2:c.191-2434_191-2433del - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.313_313+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001195798.2:c.313_313+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001195800.2:c.313_313+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001195803.2:c.313_313+1del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Homozygous familial hypercholesterolemia
Synonyms:: Familial hypercholesterolemia - homozygous
Identifiers:: MONDO: MONDO:0018328; MedGen: C0342881

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004847785	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 11, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22883975, 1301956, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004847785

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 11, 2019)

germline

clinical testing

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

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

Genetic analysis of familial hypercholesterolaemia in Western Australia.

Hooper AJ, Nguyen LT, Burnett JR, Bates TR, Bell DA, Redgrave TG, Watts GF, van Bockxmeer FM.

Atherosclerosis. 2012 Oct;224(2):430-4. doi: 10.1016/j.atherosclerosis.2012.07.030. Epub 2012 Jul 27.

PubMed [citation]

PMID:: 22883975

Molecular genetics of the LDL receptor gene in familial hypercholesterolemia.

Hobbs HH, Brown MS, Goldstein JL.

Hum Mutat. 1992;1(6):445-66. Review.

PubMed [citation]

PMID:: 1301956

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847785.1

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

Description

The c.313_313+1delCG variant in LDLR has been reported in 2 individuals with hypercholesterolemia (Hobbs 1992, Hooper 2012). It was absent from large population studies. This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. An in vitro study supports an impact on splicing (Hobbs 1992). Loss of function of the LDLR gene is an established disease mechanism in autosomal dominant familial hypercholesterolemia. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant familial hypercholesterolemia. ACMG/AMP Criteria applied: PVS1, PM2, PS4_Supporting.

#	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: May 16, 2025

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