NM_000384.3(APOB):c.10579C>T (p.Arg3527Trp) AND APOB-related disorder

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 1, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002243681.12

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:: APOB-related disorder
Synonyms:: APOB-Related Disorders; APOB-related condition
Identifiers:

Recent activity

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MULTISPECIES: SulP family inorganic anion transporter [Gammaproteobacteria]
MULTISPECIES: SulP family inorganic anion transporter [Gammaproteobacteria]
gi|566138632|ref|WP_024008860.1|

Protein
MULTISPECIES: DUF3037 domain-containing protein [Providencia]
MULTISPECIES: DUF3037 domain-containing protein [Providencia]
gi|2624042948|ref|WP_319867985.1|

Protein
Uncultured Methanothermobacter sp. isolate DGGE gel band 3Pw-A2009-6arc 16S ribo...
Uncultured Methanothermobacter sp. isolate DGGE gel band 3Pw-A2009-6arc 16S ribosomal RNA gene, partial sequence
gi|992324430|gb|KT897650.1|

Nucleotide
Uncultured Kosmotogaceae bacterium clone 37-300B-CB98 16S ribosomal RNA gene, pa...
Uncultured Kosmotogaceae bacterium clone 37-300B-CB98 16S ribosomal RNA gene, partial sequence
gi|1215529901|gb|MF470889.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002515289	Daryl Scott Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2022)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 36474027
SCV004725717	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Pathogenic (Jun 7, 2024)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002515289

Daryl Scott Lab, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 1, 2022)

unknown

clinical testing

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

SCV004725717

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Pathogenic
(Jun 7, 2024)

germline

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

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

High molecular diagnostic yields and novel phenotypic expansions involving syndromic anorectal malformations.

Belanger Deloge R, Zhao X, Luna PN, Shaw CA, Rosenfeld JA, Scott DA.

Eur J Hum Genet. 2023 Mar;31(3):296-303. doi: 10.1038/s41431-022-01255-y. Epub 2022 Dec 6.

PubMed [citation]

PMID:: 36474027
PMCID:: PMC9995493

Details of each submission

From Daryl Scott Lab, Baylor College of Medicine, SCV002515289.1

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

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

From PreventionGenetics, part of Exact Sciences, SCV004725717.2

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

Description

The APOB c.10579C>T variant is predicted to result in the amino acid substitution p.Arg3527Trp. This variant (also known as p.Arg3500Trp) has been reported in many patients with autosomal dominant hypercholesterolemia (see for example Gaffney et al. 1995. PubMed ID: 7627691; Bertolini et al. 2013. PubMed ID: 23375686; Pirillo et al. 2017. PubMed ID: 28965616). Additionally, different substitutions of the same amino acid (p.Arg3527Gln and p.Arg3527Leu) have been reported in many patients with hypercholesterolemia (see for example Soria et al. 1989. PubMed ID: 2563166; Bertolini et al. 2013. PubMed ID: 23375686; Pirillo et al. 2017. PubMed ID: 28965616; Fouchier et al. 2005. PubMed ID: 16250003), suggesting that the amino acid residue p.Arg3527 is important for proper APOB protein function. This variant is reported in 0.13% of alleles in individuals of East Asian descent in gnomAD. This variant is interpreted as pathogenic.

#	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

Last Updated: Nov 3, 2024

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