NM_000527.5(LDLR):c.668_681dup (p.Glu228fs) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 25, 2016
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:: RCV000238275.2

Allele description [Variation Report for NM_000527.5(LDLR):c.668_681dup (p.Glu228fs)]

NM_000527.5(LDLR):c.668_681dup (p.Glu228fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.668_681dup (p.Glu228fs)

HGVS:

NC_000019.10:g.11105574_11105587dup
NG_009060.1:g.21194_21207dup
NM_000527.5:c.668_681dupMANE SELECT
NM_001195798.2:c.668_681dup
NM_001195799.2:c.545_558dup
NM_001195800.2:c.314-1818_314-1805dup
NM_001195803.2:c.314-991_314-978dup
NP_000518.1:p.Glu228fs
NP_000518.1:p.Glu228fs
NP_001182727.1:p.Glu228fs
NP_001182728.1:p.Glu187fs
LRG_274t1:c.668_681dup
LRG_274:g.21194_21207dup
LRG_274p1:p.Glu228fs
NC_000019.9:g.11216250_11216263dup
NM_000527.4:c.668_681dup
c.668_681dup

Protein change:

E187fs

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000994; dbSNP: rs1555803424

NCBI 1000 Genomes Browser:

rs1555803424

Molecular consequence:

NM_000527.5:c.668_681dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.668_681dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.545_558dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.314-1818_314-1805dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-991_314-978dup - intron variant - [Sequence Ontology: SO:0001627]

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
SCV000294876	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,
SCV000599340	Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2016)	germline, not applicable	curation, literature only	PubMed (2) [See all records that cite these PMIDs] 25741868, 11916007

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000294876

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,

SCV000599340

Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 1, 2016)

germline, not applicable

curation, literature only

PubMed (2)
[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	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	yes	1	not provided	not provided	1	not provided	literature only

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Eight novel mutations and functional impairments of the LDL receptor in familial hypercholesterolemia in the north of Japan.

Hattori H, Hirayama T, Nobe Y, Nagano M, Kujiraoka T, Egashira T, Ishii J, Tsuji M, Emi M.

J Hum Genet. 2002;47(2):80-7.

PubMed [citation]

PMID:: 11916007

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000294876.2

#	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 Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge, SCV000599340.1

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

Description

"Assay Description:Htz patients' lymphocytes, FACS assays"

PubMed [ID: 11916007]

#	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	not applicable	not applicable	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 5, 2023

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