NM_015627.3(LDLRAP1):c.432_433insA (p.Ala145fs) AND Hypercholesterolemia, familial, 4

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 18, 2001
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000005040.4

Allele description [Variation Report for NM_015627.3(LDLRAP1):c.432_433insA (p.Ala145fs)]

NM_015627.3(LDLRAP1):c.432_433insA (p.Ala145fs)

Gene:

LDLRAP1:low density lipoprotein receptor adaptor protein 1 [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

1p36.11

Genomic location:

Preferred name:

NM_015627.3(LDLRAP1):c.432_433insA (p.Ala145fs)

HGVS:

NC_000001.11:g.25557240_25557241insA
NG_008932.1:g.18656_18657insA
NM_015627.3:c.432_433insAMANE SELECT
NP_056442.2:p.Ala145fs
NP_056442.2:p.Ala145fs
LRG_276t1:c.432_433insA
LRG_276:g.18656_18657insA
LRG_276p1:p.Ala145fs
NC_000001.10:g.25883731_25883732insA
NM_015627.2:c.432_433insA

Protein change:

A145fs

Links:

OMIM: 605747.0002; dbSNP: rs1557703339

NCBI 1000 Genomes Browser:

rs1557703339

Molecular consequence:

NM_015627.3:c.432_433insA - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hypercholesterolemia, familial, 4 (FHCL4)
Synonyms:: HYPERCHOLESTEROLEMIA, AUTOSOMAL RECESSIVE, 1; HYPERCHOLESTEROLEMIA, AUTOSOMAL RECESSIVE, 2; Hypercholesterolemia, autosomal recessive
Identifiers:: MONDO: MONDO:0011374; MedGen: C1863512; Orphanet: 391665; OMIM: 603813

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000025216	OMIM	no assertion criteria provided	Pathogenic (May 18, 2001)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 7628519, 11326085, 11897284

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000025216

OMIM

no assertion criteria provided

Pathogenic
(May 18, 2001)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Severe hypercholesterolaemia: unusual inheritance in an Italian pedigree.

Zuliani G, Vigna GB, Corsini A, Maioli M, Romagnoni F, Fellin R.

Eur J Clin Invest. 1995 May;25(5):322-31.

PubMed [citation]

PMID:: 7628519

Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein.

Garcia CK, Wilund K, Arca M, Zuliani G, Fellin R, Maioli M, Calandra S, Bertolini S, Cossu F, Grishin N, Barnes R, Cohen JC, Hobbs HH.

Science. 2001 May 18;292(5520):1394-8. Epub 2001 Apr 26.

PubMed [citation]

PMID:: 11326085

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000025216.3

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

Description

In 2 affected sibs from a consanguineous Sardinian family (ARH1) with autosomal recessive hypercholesterolemia (FHCL4; 603813), originally reported by Zuliani et al. (1995), Garcia et al. (2001) identified homozygosity for a 1-bp insertion (c.432insA) in exon 4 of the LDLRAP1 gene, causing a frameshift predicted to result in a premature termination codon at residue 170, within the terminal portion of the PTB domain. The plasma LDL level was about 460 mg/dl in a proband from this family. Coronary artery disease was prevalent in this family, with 8 relatives dying at less than 33 years of age.

In 4 Italian probands who had hypercholesterolemia and at least 1 normocholesterolemic parent, Arca et al. (2002) identified homozygosity for the c.432insA mutation in the LDLRAP1 gene.

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

Last Updated: Aug 5, 2023

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