NM_000527.5(LDLR):c.136T>G (p.Cys46Gly) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Jul 7, 2021
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:: RCV000238380.8

Allele description [Variation Report for NM_000527.5(LDLR):c.136T>G (p.Cys46Gly)]

NM_000527.5(LDLR):c.136T>G (p.Cys46Gly)

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.136T>G (p.Cys46Gly)

HGVS:

NC_000019.10:g.11100291T>G
NG_009060.1:g.15911T>G
NM_000527.5:c.136T>GMANE SELECT
NM_001195798.2:c.136T>G
NM_001195799.2:c.136T>G
NM_001195800.2:c.136T>G
NM_001195803.2:c.136T>G
NP_000518.1:p.Cys46Gly
NP_000518.1:p.Cys46Gly
NP_001182727.1:p.Cys46Gly
NP_001182728.1:p.Cys46Gly
NP_001182729.1:p.Cys46Gly
NP_001182732.1:p.Cys46Gly
LRG_274t1:c.136T>G
LRG_274:g.15911T>G
LRG_274p1:p.Cys46Gly
NC_000019.9:g.11210967T>G
NM_000527.4:c.136T>G
NM_001195798.1:c.136T>G
c.136T>G

Protein change:

C46G

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001206; dbSNP: rs879254415

NCBI 1000 Genomes Browser:

rs879254415

Molecular consequence:

NM_000527.5:c.136T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.136T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.136T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.136T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.136T>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000294477	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,
SCV000583634	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]
SCV000606023	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	no assertion criteria provided	Pathogenic	germline	research
SCV002556602	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 7, 2021)	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	1	not provided	1	not provided	clinical testing, literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Genetic defects causing familial hypercholesterolaemia: identification of deletions and duplications in the LDL-receptor gene and summary of all mutations found in patients attending the Hammersmith Hospital Lipid Clinic.

Tosi I, Toledo-Leiva P, Neuwirth C, Naoumova RP, Soutar AK.

Atherosclerosis. 2007 Sep;194(1):102-11. Epub 2006 Nov 13.

PubMed [citation]

PMID:: 17094996

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, SCV000294477.2

#	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 U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille, SCV000583634.1

#	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 : Probable FH

Description

ACMG Guidelines: Likely Pathogenic (ii)

#	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

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum, SCV000606023.1

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

#	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 Genetics and Molecular Pathology, SA Pathology, SCV002556602.2

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

#	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: Jun 23, 2024

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