NM_000384.3(APOB):c.4304del (p.Ile1435fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 22, 2023
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:: RCV002558787.6

Allele description [Variation Report for NM_000384.3(APOB):c.4304del (p.Ile1435fs)]

NM_000384.3(APOB):c.4304del (p.Ile1435fs)

Gene:

APOB:apolipoprotein B [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p24.1

Genomic location:

Preferred name:

NM_000384.3(APOB):c.4304del (p.Ile1435fs)

HGVS:

NC_000002.12:g.21012564del
NG_011793.1:g.36510del
NM_000384.3:c.4304delMANE SELECT
NP_000375.3:p.Ile1435fs
NC_000002.11:g.21235436del
NC_000002.11:g.21235436del

Protein change:

I1435fs

Links:

dbSNP: rs1663355633

NCBI 1000 Genomes Browser:

rs1663355633

Molecular consequence:

NM_000384.3:c.4304del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hypercholesterolemia, autosomal dominant, type B (FHCL2)
Synonyms:: APOLIPOPROTEIN B-100, FAMILIAL DEFECTIVE; APOLIPOPROTEIN B-100, FAMILIAL LIGAND-DEFECTIVE; HYPERCHOLESTEROLEMIA, FAMILIAL, DUE TO LIGAND-DEFECTIVE APOLIPOPROTEIN B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007751; MedGen: C1704417; OMIM: 144010

Name:: Familial hypobetalipoproteinemia 1
Synonyms:: Hypobetalipoproteinemia, normotriglyceridemic; Acanthocytosis with hypobetalipoproteinemia
Identifiers:: MONDO: MONDO:0014252; MedGen: C4551990; OMIM: 615558

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003310867	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 22, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20032471, 12124991, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003310867

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 22, 2023)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Nonsynonymous mutations within APOB in human familial hypobetalipoproteinemia: evidence for feedback inhibition of lipogenesis and postendoplasmic reticulum degradation of apolipoprotein B.

Zhong S, Magnolo AL, Sundaram M, Zhou H, Yao EF, Di Leo E, Loria P, Wang S, Bamji-Mirza M, Wang L, McKnight CJ, Figeys D, Wang Y, Tarugi P, Yao Z.

J Biol Chem. 2010 Feb 26;285(9):6453-64. doi: 10.1074/jbc.M109.060467. Epub 2009 Dec 23.

PubMed [citation]

PMID:: 20032471
PMCID:: PMC2825441

Novel mutations of APOB cause ApoB truncations undetectable in plasma and familial hypobetalipoproteinemia.

Yue P, Yuan B, Gerhard DS, Neuman RJ, Isley WL, Harris WS, Schonfeld G.

Hum Mutat. 2002 Aug;20(2):110-6. Erratum in: Hum Mutat 2002 Nov;20(5):402.

PubMed [citation]

PMID:: 12124991

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003310867.3

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

Description

This sequence change creates a premature translational stop signal (p.Ile1435Thrfs*6) in the APOB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APOB are known to be pathogenic (PMID: 20032471). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial hypobetalipoproteinemia (PMID: 12124991). This variant is also known as 4432delT. ClinVar contains an entry for this variant (Variation ID: 918183). For these reasons, this variant has been classified 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: May 25, 2025

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