NM_000527.5(LDLR):c.2396T>G (p.Leu799Arg) AND Hypercholesterolemia, familial, 1

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Nov 5, 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:: RCV000237210.3

Allele description [Variation Report for NM_000527.5(LDLR):c.2396T>G (p.Leu799Arg)]

NM_000527.5(LDLR):c.2396T>G (p.Leu799Arg)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.2396T>G (p.Leu799Arg)

HGVS:

NC_000019.10:g.11129519T>G
NG_009060.1:g.45139T>G
NM_000527.5:c.2396T>GMANE SELECT
NM_001195798.2:c.2396T>G
NM_001195799.2:c.2273T>G
NM_001195800.2:c.1892T>G
NM_001195803.2:c.1862T>G
NP_000518.1:p.Leu799Arg
NP_000518.1:p.Leu799Arg
NP_001182727.1:p.Leu799Arg
NP_001182728.1:p.Leu758Arg
NP_001182729.1:p.Leu631Arg
NP_001182732.1:p.Leu621Arg
LRG_274t1:c.2396T>G
LRG_274:g.45139T>G
LRG_274p1:p.Leu799Arg
NC_000019.9:g.11240195T>G
NM_000527.4:c.2396T>G
c.2396T>G

Protein change:

L621R

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000317; dbSNP: rs879255196

NCBI 1000 Genomes Browser:

rs879255196

Molecular consequence:

NM_000527.5:c.2396T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.2396T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.2273T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1892T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1862T>G - missense variant - [Sequence Ontology: SO:0001583]

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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Chain V, 26S proteasome non-ATPase regulatory subunit 3
Chain V, 26S proteasome non-ATPase regulatory subunit 3
gi|2441536661|pdb|7QXX|V

Protein
Chain r, Proteasome subunit beta type-5
Chain r, Proteasome subunit beta type-5
gi|2441536703|pdb|7QXX|r

Protein
Homo sapiens isolate CHM13 chromosome 4, alternate assembly T2T-CHM13v2.0
Homo sapiens isolate CHM13 chromosome 4, alternate assembly T2T-CHM13v2.0
gi|2194974292|gnl|ASM:GCF_009914825 f|NC_060928.1||gpp|GPC_000012743.1||gnl|NCBI_GENOMES|119564

Nucleotide
Homologene neighbors for GEO Profiles (Select 77974716) (0)
GEO Profiles

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000295990	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,
SCV000540869	Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation See additional submitters Centre of Molecular Biology and Gene Therapy, University Hospital Brno	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 5, 2016)	inherited	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 22698793
SCV000599415	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, 26220972

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000295990

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,

SCV000540869

Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 5, 2016)

inherited

clinical testing

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

SCV000599415

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	germline	yes	1	not provided	not provided	1	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation
not provided	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	literature only
Caucasian	inherited	yes	6	3	not provided	3964	yes	clinical testing

Citations

PubMed

An APEX-based genotyping microarray for the screening of 168 mutations associated with familial hypercholesterolemia.

Dušková L, Kopečková L, Jansová E, Tichý L, Freiberger T, Zapletalová P, Soška V, Ravčuková B, Fajkusová L.

Atherosclerosis. 2011 May;216(1):139-45. doi: 10.1016/j.atherosclerosis.2011.01.023. Epub 2011 Jan 21.

PubMed [citation]

PMID:: 21310417

The molecular basis of familial hypercholesterolemia in the Czech Republic: spectrum of LDLR mutations and genotype-phenotype correlations.

Tichý L, Freiberger T, Zapletalová P, Soška V, Ravčuková B, Fajkusová L.

Atherosclerosis. 2012 Aug;223(2):401-8. doi: 10.1016/j.atherosclerosis.2012.05.014. Epub 2012 May 23.

PubMed [citation]

PMID:: 22698793

See all PubMed Citations (4)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295990.2

#	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 Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation, SCV000540869.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasian	6	not provided	yes	clinical testing	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	3964	Whole blood	not provided		6	not provided	3	not provided

From Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge, SCV000599415.1

#	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:Heterologous cells (HepG2), WB and immunoprecipitation assays"

PubMed [ID: 26220972]

#	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: May 1, 2024

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