NM_000527.5(LDLR):c.1934dup (p.Asn645fs) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Mar 30, 2017
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:: RCV000237207.5

Allele description [Variation Report for NM_000527.5(LDLR):c.1934dup (p.Asn645fs)]

NM_000527.5(LDLR):c.1934dup (p.Asn645fs)

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.1934dup (p.Asn645fs)

HGVS:

NC_000019.10:g.11120180dup
NG_009060.1:g.35800dup
NM_000527.5:c.1934dupMANE SELECT
NM_001195798.2:c.1934dup
NM_001195799.2:c.1811dup
NM_001195800.2:c.1430dup
NM_001195803.2:c.1553dup
NP_000518.1:p.Asn645fs
NP_000518.1:p.Asn645fs
NP_001182727.1:p.Asn645fs
NP_001182728.1:p.Asn604fs
NP_001182729.1:p.Asn477fs
NP_001182732.1:p.Asn518fs
LRG_274t1:c.1934dup
LRG_274:g.35800dup
LRG_274p1:p.Asn645fs
NC_000019.9:g.11230856dup
NM_000527.4:c.1934dup
c.1934dupA
p.Asn645Lysfs*24

Protein change:

N477fs

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001554; dbSNP: rs879255076

NCBI 1000 Genomes Browser:

rs879255076

Molecular consequence:

NM_000527.5:c.1934dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.1934dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.1811dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.1430dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.1553dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

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RecName: Full=Palmitoyltransferase ZDHHC20; AltName: Full=Acyltransferase ZDHHC2...
RecName: Full=Palmitoyltransferase ZDHHC20; AltName: Full=Acyltransferase ZDHHC20; AltName: Full=DHHC domain-containing cysteine-rich protein 20; Short=DHHC20; AltName: Full=Zinc finger DHHC domain-containing protein 20
gi|74748004|sp|Q5W0Z9.1|ZDH20_HUMAN

Protein
cpsf2 cleavage and polyadenylation specific factor 2 [Danio rerio]
cpsf2 cleavage and polyadenylation specific factor 2 [Danio rerio]
Gene ID:436657

Gene
Gene Links for GEO Profiles (Select 131544893) (1)
Gene
NINJ1 ninjurin 1 [Homo sapiens]
NINJ1 ninjurin 1 [Homo sapiens]
Gene ID:4814

Gene
Homologene neighbors for GEO Profiles (Select 131544893) (0)
GEO Profiles

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000295758	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,
SCV000322988	Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2016)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV000503434	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)	Pathogenic (Dec 16, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000583909	U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 30, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	1	not provided	2601	not provided	clinical testing, research, literature only

Citations

PubMed

Molecular spectrum of autosomal dominant hypercholesterolemia in France.

Marduel M, Carrié A, Sassolas A, Devillers M, Carreau V, Di Filippo M, Erlich D, Abifadel M, Marques-Pinheiro A, Munnich A, Junien C; French ADH Research Network., Boileau C, Varret M, Rabès JP.

Hum Mutat. 2010 Nov;31(11):E1811-24. doi: 10.1002/humu.21348.

PubMed [citation]

PMID:: 20809525
PMCID:: PMC3152176

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

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295758.2

#	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, SCV000322988.1

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

Description

0/200 non-FH alleles

#	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		not provided	not provided	not provided	not provided
2	germline	yes	not provided	not provided	not provided		not provided	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, SCV000503434.1

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

Description

subject mutated among 2600 FH index cases screened = 1, family member=1

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

From U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille, SCV000583909.1

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

Description

Dutch Lipid Clinic Scoring : Definite FH

#	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		1	not provided	1	not provided

Last Updated: Jun 23, 2024

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