NM_000527.5(LDLR):c.139_144del (p.Asp47_Gly48del) AND Hypercholesterolemia, familial, 1

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Mar 25, 2016
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:: RCV000237855.14

Allele description [Variation Report for NM_000527.5(LDLR):c.139_144del (p.Asp47_Gly48del)]

NM_000527.5(LDLR):c.139_144del (p.Asp47_Gly48del)

Gene:

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.139_144del (p.Asp47_Gly48del)

Other names:

FH Cape Town-1; FH Pedi Tswana

HGVS:

NC_000019.10:g.11100294_11100299del
NG_009060.1:g.15914_15919del
NG_009060.1:g.15914_15919delGATGGC
NM_000527.5:c.139_144delMANE SELECT
NM_001195798.2:c.139_144del
NM_001195799.2:c.139_144del
NM_001195800.2:c.139_144del
NM_001195803.2:c.139_144del
NP_000518.1:p.Asp47_Gly48del
NP_000518.1:p.Asp47_Gly48del
NP_001182727.1:p.Asp47_Gly48del
NP_001182728.1:p.Asp47_Gly48del
NP_001182729.1:p.Asp47_Gly48del
NP_001182732.1:p.Asp47_Gly48del
LRG_274t1:c.139_144del
LRG_274:g.15914_15919del
LRG_274p1:p.Asp47_Gly48del
NC_000019.9:g.11210970_11210975del
NG_009060.1:g.15914_15919delGATGGC
NM_000527.4:c.139_144del
c.139_144del

Nucleotide change:

ASP26/GLY27DEL

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001414; OMIM: 606945.0002; dbSNP: rs387906301

NCBI 1000 Genomes Browser:

rs387906301

Molecular consequence:

NM_000527.5:c.139_144del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195798.2:c.139_144del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195799.2:c.139_144del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195800.2:c.139_144del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195803.2:c.139_144del - inframe_deletion - [Sequence Ontology: SO:0001822]

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
SCV000024034	OMIM	no assertion criteria provided	Pathogenic (Jul 1, 2000)	germline	literature only	PubMed (1) [See all records that cite this PMID] Leitersdorf, E., Hobbs, H. H. Personal Communication. 1990. Dallas, Tex.,
SCV000294482	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Likely pathogenic (Mar 25, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000599313	Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 1, 2016)	germline, not applicable	curation, literature only	PubMed (2) [See all records that cite these PMIDs] 25741868, 1301956

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000024034

OMIM

no assertion criteria provided

Pathogenic
(Jul 1, 2000)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Leitersdorf, E., Hobbs, H. H. Personal Communication. 1990. Dallas, Tex.,

SCV000294482

LDLR-LOVD, British Heart Foundation

criteria provided, single submitter

(ACGS Guidelines, 2013)

Likely pathogenic
(Mar 25, 2016)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV000599313

Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 1, 2016)

germline, not applicable

curation, literature only

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	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	yes	1	not provided	not provided	1	not provided	literature only
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia.

Thiart R, Scholtz CL, Vergotine J, Hoogendijk CF, de Villiers JN, Nissen H, Brusgaard K, Gaffney D, Hoffs MS, Vermaak WJ, Kotze MJ.

J Med Genet. 2000 Jul;37(7):514-9.

PubMed [citation]

PMID:: 10882754
PMCID:: PMC1734636

Deletion in the first cysteine-rich repeat of low density lipoprotein receptor impairs its transport but not lipoprotein binding in fibroblasts from a subject with familial hypercholesterolemia.

Leitersdorf E, Hobbs HH, Fourie AM, Jacobs M, van der Westhuyzen DR, Coetzee GA.

Proc Natl Acad Sci U S A. 1988 Nov;85(21):7912-6.

PubMed [citation]

PMID:: 3263645
PMCID:: PMC282319

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000024034.3

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

Description

In a South African black with FH (FHCL1; 143890), Leitersdorf et al. (1988) demonstrated deletion of aspartic acid-26 and glycine-27 due to deletion of the 6 nucleotides of codons 26 and 27: GCGATG.

Thiart et al. (2000) found this mutation in 28% of mutant alleles in 56 South African black patients.

#	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

From LDLR-LOVD, British Heart Foundation, SCV000294482.2

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

#	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

From Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge, SCV000599313.1

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

Description

"Assay Description:Hmz patients' fibroblasts, 125I-LDL assays"

PubMed [ID: 1301956]

#	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	not applicable	not applicable	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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