NM_000527.5(LDLR):c.82G>T (p.Glu28Ter) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Nov 1, 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:: RCV000211620.7

Allele description [Variation Report for NM_000527.5(LDLR):c.82G>T (p.Glu28Ter)]

NM_000527.5(LDLR):c.82G>T (p.Glu28Ter)

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.82G>T (p.Glu28Ter)

HGVS:

NC_000019.10:g.11100237G>T
NG_009060.1:g.15857G>T
NM_000527.5:c.82G>TMANE SELECT
NM_001195798.2:c.82G>T
NM_001195799.2:c.82G>T
NM_001195800.2:c.82G>T
NM_001195803.2:c.82G>T
NP_000518.1:p.Glu28Ter
NP_000518.1:p.Glu28Ter
NP_001182727.1:p.Glu28Ter
NP_001182728.1:p.Glu28Ter
NP_001182729.1:p.Glu28Ter
NP_001182732.1:p.Glu28Ter
LRG_274t1:c.82G>T
LRG_274:g.15857G>T
LRG_274p1:p.Glu28Ter
NC_000019.9:g.11210913G>T
NM_000527.4:c.82G>T
c.82G>T

Protein change:

E28*

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000023; dbSNP: rs551747280

NCBI 1000 Genomes Browser:

rs551747280

Molecular consequence:

NM_000527.5:c.82G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001195798.2:c.82G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001195799.2:c.82G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001195800.2:c.82G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001195803.2:c.82G>T - nonsense - [Sequence Ontology: SO:0001587]

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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000268539	Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA - Fiona Stanley Hospital	no assertion criteria provided	Pathogenic (Jul 10, 2013)	germline	clinical testing
SCV000294456	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Pathogenic (Mar 25, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000606009	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	no assertion criteria provided	Pathogenic	germline	research
SCV004175362	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 1, 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	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

Low-density lipoprotein receptor gene familial hypercholesterolemia variant database: update and pathological assessment.

Usifo E, Leigh SE, Whittall RA, Lench N, Taylor A, Yeats C, Orengo CA, Martin AC, Celli J, Humphries SE.

Ann Hum Genet. 2012 Sep;76(5):387-401. doi: 10.1111/j.1469-1809.2012.00724.x.

PubMed [citation]

PMID:: 22881376

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, SCV000268539.1

#	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, SCV000294456.2

#	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, SCV000606009.1

#	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, SCV004175362.1

#	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: Dec 17, 2023

ClinVar

Relating variation to medicine