NM_000527.5(LDLR):c.660del (p.Asp221fs) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: May 11, 2019
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:: RCV000211699.7

Allele description [Variation Report for NM_000527.5(LDLR):c.660del (p.Asp221fs)]

NM_000527.5(LDLR):c.660del (p.Asp221fs)

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.660del (p.Asp221fs)

HGVS:

NC_000019.10:g.11105566del
NC_000019.9:g.11216239del
NG_009060.1:g.21186del
NM_000527.5:c.660delMANE SELECT
NM_001195798.2:c.660del
NM_001195799.2:c.537del
NM_001195800.2:c.314-1826del
NM_001195803.2:c.314-999del
NP_000518.1:p.Asp221fs
NP_001182727.1:p.Asp221fs
NP_001182728.1:p.Asp180fs
LRG_274t1:c.660del
LRG_274:g.21186del
NC_000019.9:g.11216239del
NC_000019.9:g.11216242del
NC_000019.9:g.11216242delC
NM_000527.4:c.660delC
c.660delC

Protein change:

D180fs

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000679; dbSNP: rs875989905

NCBI 1000 Genomes Browser:

rs875989905

Molecular consequence:

NM_000527.5:c.660del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.660del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.537del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.314-1826del - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-999del - intron variant - [Sequence Ontology: SO:0001627]

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
SCV000268575	Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA - Fiona Stanley Hospital	no assertion criteria provided	Pathogenic (May 5, 2014)	germline	clinical testing
SCV000294857	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Pathogenic (Mar 25, 2016)	germline	literature only	PubMed (4) [See all records that cite these PMIDs] 11462246, 11139254, 15556094, 17539906 Citation Link,
SCV000606183	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	no assertion criteria provided	Pathogenic	germline	research
SCV001432618	Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 11, 2019)	germline	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 31345425

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	9	not provided	not provided	5	not provided	clinical testing, literature only, research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Identification of recurrent and novel mutations in the LDL receptor gene in German patients with familial hypercholesterolemia.

Nauck MS, Köster W, Dörfer K, Eckes J, Scharnagl H, Gierens H, Nissen H, Nauck MA, Wieland H, März W.

Hum Mutat. 2001 Aug;18(2):165-6.

PubMed [citation]

PMID:: 11462246

Eight novel LDL receptor gene mutations among patients under LDL apheresis in Dresden and Leipzig.

Bochmann H, Geisel J, Herrmann W, Purcz T, Reuter W, Julius U, Metzler W, Bergmann S, Jaross W, Gehrisch S.

Hum Mutat. 2001;17(1):76-7.

PubMed [citation]

PMID:: 11139254

See all PubMed Citations (6)

Details of each submission

From Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA - Fiona Stanley Hospital, SCV000268575.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	not provided

#	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		4	not provided	not provided	not provided

From LDLR-LOVD, British Heart Foundation, SCV000294857.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	literature only	PubMed (4)
2	not provided	1	not provided	not provided	literature only	PubMed (4)
3	not provided	1	not provided	not provided	literature only	PubMed (4)
4	not provided	1	not provided	not provided	literature only	PubMed (4)

#	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
2	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
3	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
4	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum, SCV000606183.1

#	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 Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia, SCV001432618.1

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

#	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

Last Updated: Feb 25, 2025

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