NM_000527.5(LDLR):c.224G>A (p.Cys75Tyr) AND Hypercholesterolemia, familial, 1

Germline classification:: Likely pathogenic (4 submissions)
Last evaluated:: Aug 19, 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:: RCV000211622.9

Allele description [Variation Report for NM_000527.5(LDLR):c.224G>A (p.Cys75Tyr)]

NM_000527.5(LDLR):c.224G>A (p.Cys75Tyr)

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.224G>A (p.Cys75Tyr)

HGVS:

NC_000019.10:g.11102697G>A
NG_009060.1:g.18317G>A
NM_000527.5:c.224G>AMANE SELECT
NM_001195798.2:c.224G>A
NM_001195799.2:c.190+2352G>A
NM_001195800.2:c.224G>A
NM_001195803.2:c.224G>A
NP_000518.1:p.Cys75Tyr
NP_000518.1:p.Cys75Tyr
NP_001182727.1:p.Cys75Tyr
NP_001182729.1:p.Cys75Tyr
NP_001182732.1:p.Cys75Tyr
LRG_274t1:c.224G>A
LRG_274:g.18317G>A
LRG_274p1:p.Cys75Tyr
NC_000019.9:g.11213373G>A
NM_000527.4:c.224G>A
c.224G>A

Protein change:

C75Y

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000686; dbSNP: rs875989890

NCBI 1000 Genomes Browser:

rs875989890

Molecular consequence:

NM_001195799.2:c.190+2352G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.224G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.224G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.224G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.224G>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000268542	Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA - Fiona Stanley Hospital	no assertion criteria provided	Pathogenic (Jun 21, 2013)	germline	clinical testing
SCV000294536	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,
SCV000606043	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	no assertion criteria provided	Pathogenic	germline	research
SCV002579490	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 19, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	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

Mutation analysis of exon 3 of the LDL receptor gene in patients with severe hypercholesterolemia.

Geisel J, Gielen J, Oette K, Herrmann W, Wielckens K.

Clin Chem Lab Med. 1998 May;36(5):279-82.

PubMed [citation]

PMID:: 9676383

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 Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA - Fiona Stanley Hospital, SCV000268542.1

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

#	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	not provided	not provided

From LDLR-LOVD, British Heart Foundation, SCV000294536.2

#	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 Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum, SCV000606043.1

#	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 MGZ Medical Genetics Center, SCV002579490.1

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

Last Updated: May 7, 2024

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