NM_000384.3(APOB):c.13477CAG[1] (p.Gln4494del) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 12, 2024
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:: RCV001283874.12

Allele description [Variation Report for NM_000384.3(APOB):c.13477CAG[1] (p.Gln4494del)]

NM_000384.3(APOB):c.13477CAG[1] (p.Gln4494del)

Gene:

APOB:apolipoprotein B [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

2p24.1

Genomic location:

Preferred name:

NM_000384.3(APOB):c.13477CAG[1] (p.Gln4494del)

HGVS:

NC_000002.12:g.21001940CTG[1]
NC_000002.12:g.21001940_21001942delCTG
NG_011793.1:g.47129CAG[1]
NG_042877.1:g.1641_1642insG
NM_000384.3:c.13477CAG[1]MANE SELECT
NP_000375.3:p.Gln4494del
NC_000002.11:g.21224812CTG[1]
NC_000002.11:g.21224812_21224814del
NC_000002.11:g.21224812_21224814delCTG
NM_000384.2:c.13480_13482delCAG
NM_000384.3:c.13480_13482delMANE SELECT
NP_000375.2:p.Q4494del

Protein change:

Q4494del

Links:

dbSNP: rs562574661

NCBI 1000 Genomes Browser:

rs562574661

Molecular consequence:

NM_000384.3:c.13477CAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001469332	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jun 12, 2024)	unknown	clinical testing	PubMed (15) [See all records that cite these PMIDs] 32770674, 32719484, 33269076, 33418990, 33508743, 29386597, 31980526, 33303402, 24234650, 26643808, 36190978, 36648309, 36196022, 35913489, 26467025
SCV003921569	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Nov 30, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001469332

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jun 12, 2024)

unknown

clinical testing

PubMed (15)
[See all records that cite these PMIDs]

SCV003921569

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Nov 30, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia.

Rieck L, Bardey F, Grenkowitz T, Bertram L, Helmuth J, Mischung C, Spranger J, Steinhagen-Thiessen E, Bobbert T, Kassner U, Demuth I.

Clin Genet. 2020 Nov;98(5):457-467. doi: 10.1111/cge.13826. Epub 2020 Sep 2.

PubMed [citation]

PMID:: 32770674

Population genetic screening efficiently identifies carriers of autosomal dominant diseases.

Grzymski JJ, Elhanan G, Morales Rosado JA, Smith E, Schlauch KA, Read R, Rowan C, Slotnick N, Dabe S, Metcalf WJ, Lipp B, Reed H, Sharma L, Levin E, Kao J, Rashkin M, Bowes J, Dunaway K, Slonim A, Washington N, Ferber M, Bolze A, et al.

Nat Med. 2020 Aug;26(8):1235-1239. doi: 10.1038/s41591-020-0982-5. Epub 2020 Jul 27.

PubMed [citation]

PMID:: 32719484

See all PubMed Citations (15)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001469332.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (15)

Description

The APOB c.13480_13482del (p.Gln4494del) variant has been reported in the published literature in individuals affected with hypercholesterolemia (PMIDs: 31980526 (2020), 32770674 (2020), 33269076 (2021), 33303402 (2021), 33418990 (2021), and 35913489 (2022)), and did not fully co-segregate in one family (PMID: 24234650 (2014)). Additionally, functional studies have shown this variant caused impaired LDL binding and uptake (PMIDs: 24234650 (2014) and 26643808 (2015)). The frequency of this variant in the general population, 0.0007 (90/128394 chromosomes in European (Non-Finnish) subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. ClinVar contains an entry for this variant (URL: www.ncbi.nlm.nih.gov/clinvar, Variation ID: 265896). Based on the available information, we are unable to determine the clinical significance of this variant.

#	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		not provided	not provided	not provided	not provided

From GeneDx, SCV003921569.1

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

Description

Published functional studies demonstrate a damaging effect through a 40% decrease in internalization in lymphocytes and HepG2 cells (Alves et al., 2014); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26643808, 24234650, 32719484, 32770674, 33269076, 33418990, 33303402, 35913489, 31980526)

#	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

Last Updated: Mar 11, 2025

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