NM_000384.3(APOB):c.10579C>T (p.Arg3527Trp) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Aug 22, 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:: RCV000408839.16

Allele description [Variation Report for NM_000384.3(APOB):c.10579C>T (p.Arg3527Trp)]

NM_000384.3(APOB):c.10579C>T (p.Arg3527Trp)

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.10579C>T (p.Arg3527Trp)

Other names:

9774C>T

HGVS:

NC_000002.12:g.21006289G>A
NG_011793.1:g.42785C>T
NM_000384.3:c.10579C>TMANE SELECT
NP_000375.2:p.Arg3527Trp
NP_000375.3:p.Arg3527Trp
NC_000002.11:g.21229161G>A
NM_000384.2:c.10579C>T
NM_000384.3(APOB):c.10579C>TMANE SELECT
NP_000375.2:p.R3527W

Protein change:

R3527W; Arg3500Trp

Links:

dbSNP: rs144467873

NCBI 1000 Genomes Browser:

rs144467873

Molecular consequence:

NM_000384.3:c.10579C>T - 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
SCV000484822	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]
SCV000605967	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	no assertion criteria provided	Pathogenic	germline	research
SCV001432580	Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 18, 2019)	germline	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 31345425

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000484822

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]

SCV000605967

Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum

no assertion criteria provided

Pathogenic

germline

research

SCV001432580

Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 18, 2019)

germline

research

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	germline	yes	3	not provided	not provided	2	not provided	clinical testing, research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

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

Independent mutations at codon 3500 of the apolipoprotein B gene are associated with hyperlipidemia.

Gaffney D, Reid JM, Cameron IM, Vass K, Caslake MJ, Shepherd J, Packard CJ.

Arterioscler Thromb Vasc Biol. 1995 Aug;15(8):1025-9.

PubMed [citation]

PMID:: 7627691

See all PubMed Citations (4)

Details of each submission

From Robarts Research Institute, Western University, SCV000484822.2

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

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum, SCV000605967.1

#	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, SCV000607383.1

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

Description

%MAF(ExAC):0.01651

"Htz patient LDL, U937 cells proliferation assays"

PubMed [ID: 7627691]

#	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, SCV001432580.1

#	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)

#	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

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000607383	Fundacion Hipercolesterolemia Familiar - SAFEHEART	flagged submission Reason: Claim with insufficient supporting evidence Notes: None (ACMG Guidelines, 2015)	Uncertain significance (Mar 1, 2016)	germline	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 7627691

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000607383

Fundacion Hipercolesterolemia Familiar - SAFEHEART

flagged submission

Reason: Claim with insufficient supporting evidence

Notes: None

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 1, 2016)

germline

research

PubMed (2)
[See all records that cite these PMIDs]

Last Updated: Nov 10, 2024

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