NM_000527.5(LDLR):c.1880C>T (p.Ala627Val) AND Hypercholesterolemia, familial, 1

Germline classification:: Likely pathogenic (3 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:: RCV000237121.4

Allele description [Variation Report for NM_000527.5(LDLR):c.1880C>T (p.Ala627Val)]

NM_000527.5(LDLR):c.1880C>T (p.Ala627Val)

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.1880C>T (p.Ala627Val)

HGVS:

NC_000019.10:g.11120126C>T
NG_009060.1:g.35746C>T
NM_000527.5:c.1880C>TMANE SELECT
NM_001195798.2:c.1880C>T
NM_001195799.2:c.1757C>T
NM_001195800.2:c.1376C>T
NM_001195803.2:c.1499C>T
NP_000518.1:p.Ala627Val
NP_000518.1:p.Ala627Val
NP_001182727.1:p.Ala627Val
NP_001182728.1:p.Ala586Val
NP_001182729.1:p.Ala459Val
NP_001182732.1:p.Ala500Val
LRG_274t1:c.1880C>T
LRG_274:g.35746C>T
LRG_274p1:p.Ala627Val
NC_000019.9:g.11230802C>T
NM_000527.4:c.1880C>T
c.1880C>T

Protein change:

A459V

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000658; dbSNP: rs875989934

NCBI 1000 Genomes Browser:

rs875989934

Molecular consequence:

NM_000527.5:c.1880C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1880C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1757C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1376C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1499C>T - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000295738	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,
SCV000503430	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]
SCV000583905	U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 30, 2017)	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

SCV000295738

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,

SCV000503430

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]

SCV000583905

U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 30, 2017)

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	5	1	not provided	2601	not provided	clinical testing, literature only

Citations

PubMed

Mutations in the low-density lipoprotein receptor gene in Chinese familial hypercholesterolemia patients.

Mak YT, Pang CP, Tomlinson B, Zhang J, Chan YS, Mak TW, Masarei JR.

Arterioscler Thromb Vasc Biol. 1998 Oct;18(10):1600-5.

PubMed [citation]

PMID:: 9763532

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295738.2

#	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 Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix, SCV000503430.1

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

Description

subjects mutated among 2600 FH index cases screened = 3, 1 homozygote with co-segregation / Other mutation at same codon/software prediction 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		3	not provided	not provided	not provided

From U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille, SCV000583905.1

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

Description

Dutch Lipid Clinic Scoring : Possible 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		1	not provided	1	not provided

Last Updated: Sep 29, 2024

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