NM_000527.5(LDLR):c.428G>A (p.Cys143Tyr) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Mar 30, 2017
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:: RCV000238346.6

Allele description [Variation Report for NM_000527.5(LDLR):c.428G>A (p.Cys143Tyr)]

NM_000527.5(LDLR):c.428G>A (p.Cys143Tyr)

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.428G>A (p.Cys143Tyr)

HGVS:

NC_000019.10:g.11105334G>A
NG_009060.1:g.20954G>A
NM_000527.5:c.428G>AMANE SELECT
NM_001195798.2:c.428G>A
NM_001195799.2:c.305G>A
NM_001195800.2:c.314-2058G>A
NM_001195803.2:c.314-1231G>A
NP_000518.1:p.Cys143Tyr
NP_000518.1:p.Cys143Tyr
NP_001182727.1:p.Cys143Tyr
NP_001182728.1:p.Cys102Tyr
LRG_274t1:c.428G>A
LRG_274:g.20954G>A
LRG_274p1:p.Cys143Tyr
NC_000019.9:g.11216010G>A
NM_000527.4:c.428G>A
c.428G>A

Protein change:

C102Y

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000059; dbSNP: rs879254522

NCBI 1000 Genomes Browser:

rs879254522

Molecular consequence:

NM_001195800.2:c.314-2058G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1231G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.428G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.428G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.305G>A - 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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receptor activity-modifying protein 1 precursor [Danio rerio]
receptor activity-modifying protein 1 precursor [Danio rerio]
gi|50540458|ref|NP_001002693.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000294706	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Likely pathogenic (Mar 25, 2016)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 11295843, 14570618, 19073363 Citation Link,
SCV000503156	Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 16, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000583675	U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 30, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000599331	Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2016)	germline, not applicable	curation, literature only	PubMed (2) [See all records that cite these PMIDs] 25741868, 19073363

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	8	1	not provided	2603	not provided	clinical testing, 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

Citations

PubMed

Two novel LDL receptor mutations in familial hypercholesterolemia: C122Y and E296X.

Genschel J, Thomas HP, Kassner U, Lochs H, Steinhagen-Thiessen E, Schmidt HH.

Hum Mutat. 2001 Apr;17(4):354. No abstract available.

PubMed [citation]

PMID:: 11295843

Analysis of low-density lipoprotein receptor gene mutations in a Chinese patient with clinically homozygous familial hypercholesterolemia.

Cao S, Wang L, Qin Y, Lin J, Wu B, Liu S, Pan X, Du L, Chen B.

Chin Med J (Engl). 2003 Oct;116(10):1535-8.

PubMed [citation]

PMID:: 14570618

See all PubMed Citations (4)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000294706.2

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

#	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
3	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix, SCV000503156.1

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

Description

subject mutated among 2600 FH index cases screened = 1 / Software predictions: Damaging

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	2600	not provided	not provided		1	not provided	not provided	not provided

From U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille, SCV000583675.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	PubMed (1)

Description

Dutch Lipid Clinic Scoring : Definite FH

#	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		4	not provided	1	not provided

From Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge, SCV000599331.1

#	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 (HEK 293), WB, FACS assays"

PubMed [ID: 19073363]

#	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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