NM_000527.5(LDLR):c.214del (p.Asp72fs) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Mar 1, 2018
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:: RCV000238154.2

Allele description [Variation Report for NM_000527.5(LDLR):c.214del (p.Asp72fs)]

NM_000527.5(LDLR):c.214del (p.Asp72fs)

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.214del (p.Asp72fs)

HGVS:

NC_000019.10:g.11102687del
NC_000019.9:g.11213360del
NG_009060.1:g.18307del
NM_000527.5:c.214delMANE SELECT
NM_001195798.2:c.214del
NM_001195799.2:c.190+2342del
NM_001195800.2:c.214del
NM_001195803.2:c.214del
NP_000518.1:p.Asp72fs
NP_001182727.1:p.Asp72fs
NP_001182729.1:p.Asp72fs
NP_001182732.1:p.Asp72fs
LRG_274:g.18307del
NC_000019.10:g.11102687delG
NC_000019.9:g.11213360del
NC_000019.9:g.11213363del
NC_000019.9:g.11213363delG
NM_000527.4:c.214delG
c.214delG

Protein change:

D72fs

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001604; dbSNP: rs879254438

NCBI 1000 Genomes Browser:

rs879254438

Molecular consequence:

NM_000527.5:c.214del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.214del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.214del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.214del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.190+2342del - intron variant - [Sequence Ontology: SO:0001627]

Observations:

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

Recent activity

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ST8SIA6 [Pelecanus crispus]
ST8SIA6 [Pelecanus crispus]
Gene ID:104035235

Gene
Dilated cardiomyopathy 1G
Dilated cardiomyopathy 1G

MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000294534	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Pathogenic (Mar 25, 2016)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 10790219, 8645375 Citation Link,
SCV000607431	Fundacion Hipercolesterolemia Familiar - SAFEHEART	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2016)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV000987021	Department of Human Genetics, Laborarztpraxis Dres. Walther, Weindel und Kollegen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000294534

LDLR-LOVD, British Heart Foundation

criteria provided, single submitter

(ACGS Guidelines, 2013)

Pathogenic
(Mar 25, 2016)

germline

literature only

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

Citation Link,

SCV000607431

Fundacion Hipercolesterolemia Familiar - SAFEHEART

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 1, 2016)

germline

research

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

SCV000987021

Department of Human Genetics, Laborarztpraxis Dres. Walther, Weindel und Kollegen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 1, 2018)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	2	not provided	clinical testing, literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Mutation analysis in 36 unrelated Spanish subjects with familial hypercholesterolemia: identification of 3 novel mutations in the LDL receptor gene.

Mozas P, Cenarro A, Civeira F, Castillo S, Ros E, Pocovi M.

Hum Mutat. 2000 May;15(5):483-4.

PubMed [citation]

PMID:: 10790219

A novel single base deletion in the LDLR gene (211delG): Effect on serum lipid profiles and the influence of other genetic polymorphisms in the ACE, APOE and APOB genes.

Ward AJ, O'Kane M, Nicholls DP, Young IS, Nevin NC, Graham CA.

Atherosclerosis. 1996 Feb;120(1-2):83-91.

PubMed [citation]

PMID:: 8645375

See all PubMed Citations (3)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000294534.2

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

#	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
2	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Fundacion Hipercolesterolemia Familiar - SAFEHEART, SCV000607431.1

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

Description

%MAF(ExAC):0.0008236

#	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

From Department of Human Genetics, Laborarztpraxis Dres. Walther, Weindel und Kollegen, SCV000987021.1

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

Description

The mutation leads to the amino acid exchange asparagine to threonine at position 72 at protein level, as well as a premature termination of protein synthesis. This variant was previously observed in patients with FH under the legacy name c.211delG. We observed this variant in a patient with TC up to 320 mg/dl and LDL-C approx 290 mg/dl at the age of 35. PMID: 8645375 10790219

#	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: Sep 29, 2024

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