NM_000384.3(APOB):c.10580G>A (p.Arg3527Gln) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic/Likely pathogenic (9 submissions)
Last evaluated:: Jun 9, 2022
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:: RCV000019479.55

Allele description [Variation Report for NM_000384.3(APOB):c.10580G>A (p.Arg3527Gln)]

NM_000384.3(APOB):c.10580G>A (p.Arg3527Gln)

Gene:

APOB:apolipoprotein B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p24.1

Genomic location:

Preferred name:

NM_000384.3(APOB):c.10580G>A (p.Arg3527Gln)

Other names:

R3500Q; 9775G>A

HGVS:

NC_000002.12:g.21006288C>T
NG_011793.1:g.42786G>A
NM_000384.3:c.10580G>AMANE SELECT
NP_000375.2:p.Arg3527Gln
NP_000375.3:p.Arg3527Gln
NC_000002.11:g.21229160C>T
NM_000384.2:c.10580G>A
NM_000384.3(APOB):c.10580G>AMANE SELECT
NP_000375.2:p.R3527Q
p.ARG3527GLN

Protein change:

R3527Q; Arg3500Gln

Links:

OMIM: 107730.0009

Molecular consequence:

NM_000384.3:c.10580G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000212143	Institute for Integrative and Experimental Genomics, University of Luebeck	criteria provided, single submitter (Submitter's publication)	Likely pathogenic	germline	research	PubMed (1) [See all records that cite this PMID]
SCV000322853	Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2016)	germline	research	PubMed (3) [See all records that cite these PMIDs] 25741868, 2280177, 26643808
SCV000484820	Robarts Research Institute, Western University	criteria provided, single submitter (Wang et al. (Arterioscler Thromb Vasc Biol. 2016))	Pathogenic (Aug 22, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000588451	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 (3) [See all records that cite these PMIDs] 25741868, 2280177, 26643808
SCV000605966	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	no assertion criteria provided	Pathogenic	germline	research
SCV000607384	Fundacion Hipercolesterolemia Familiar - SAFEHEART	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2016)	germline	research	PubMed (3) [See all records that cite these PMIDs] 25741868, 2280177, 26643808
SCV000748075	Iberoamerican FH Network	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2016)	germline	research	PubMed (3) [See all records that cite these PMIDs] 25741868, 2280177, 26643808
SCV001432581	Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 23, 2019)	germline	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 31345425
SCV002580122	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 9, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	39	3	not provided	13	not provided	clinical testing, research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Systematic analysis of variants related to familial hypercholesterolemia in families with premature myocardial infarction.

Brænne I, Kleinecke M, Reiz B, Graf E, Strom T, Wieland T, Fischer M, Kessler T, Hengstenberg C, Meitinger T, Erdmann J, Schunkert H.

Eur J Hum Genet. 2016 Feb;24(2):191-7. doi: 10.1038/ejhg.2015.100. Epub 2015 Jun 3.

PubMed [citation]

PMID:: 26036859
PMCID:: PMC4717192

Polygenic Versus Monogenic Causes of Hypercholesterolemia Ascertained Clinically.

Wang J, Dron JS, Ban MR, Robinson JF, McIntyre AD, Alazzam M, Zhao PJ, Dilliott AA, Cao H, Huff MW, Rhainds D, Low-Kam C, Dubé MP, Lettre G, Tardif JC, Hegele RA.

Arterioscler Thromb Vasc Biol. 2016 Dec;36(12):2439-2445. Epub 2016 Oct 20.

PubMed [citation]

PMID:: 27765764

See all PubMed Citations (6)

Details of each submission

From Institute for Integrative and Experimental Genomics, University of Luebeck, SCV000212143.1

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

#	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	3	not provided

From Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge, SCV000322853.1

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

Description

%MAF (ExAC):0.02311

"Heterozygous patient LDL, U937 cells proliferation / Heterologous cells (HepG2), FACS assays"

PubMed [ID: 2280177]

Description

0/190 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 Robarts Research Institute, Western University, SCV000484820.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	20	not provided	not provided	clinical testing	PubMed (1)

#	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		20	not provided	not provided	not provided

From Laboratory of Genetics and Molecular Cardiology, University of São Paulo - HipercolBrasil, SCV000588451.1

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

Description

%MAF(ExAC):0.02311

"Assay description:Htz patient LDL, U937 cells proliferation / Heterologous cells (HepG2), FACS assays"

PubMed [ID: 2280177]

#	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, SCV000605966.1

#	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 Fundacion Hipercolesterolemia Familiar - SAFEHEART, SCV000607384.1

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

Description

%MAF(ExAC):0.02311

"Htz patient LDL, U937 cells proliferation / Heterologous cells (HepG2), FACS assays"

PubMed [ID: 2280177]

#	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 Iberoamerican FH Network, SCV000748075.1

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

Description

%MAF(ExAC):0.02311

"Assay Description:Htz patient LDL, U937 cells proliferation / Heterologous cells (HepG2), FACS assays"

PubMed [ID: 2280177]

#	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 Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia, SCV001432581.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (2)
2	not provided	1	not provided	not provided	research	PubMed (2)
3	not provided	1	not provided	not provided	research	PubMed (2)
4	not provided	1	not provided	not provided	research	PubMed (2)
5	not provided	1	not provided	not provided	research	PubMed (2)
6	not provided	1	not provided	not provided	research	PubMed (2)
7	not provided	1	not provided	not provided	research	PubMed (2)
8	not provided	1	not provided	not provided	research	PubMed (2)
9	not provided	1	not provided	not provided	research	PubMed (2)
10	not provided	1	not provided	not provided	research	PubMed (2)
11	not provided	1	not provided	not provided	research	PubMed (2)
12	not provided	1	not provided	not provided	research	PubMed (2)
13	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
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
5	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
6	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
7	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
8	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
9	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
10	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
11	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
12	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
13	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From MGZ Medical Genetics Center, SCV002580122.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	6	not provided	not provided	clinical testing	PubMed (1)

#	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		6	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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