NM_000527.5(LDLR):c.2072C>A (p.Ser691Ter) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 5, 2016
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:: RCV000238487.2

Allele description [Variation Report for NM_000527.5(LDLR):c.2072C>A (p.Ser691Ter)]

NM_000527.5(LDLR):c.2072C>A (p.Ser691Ter)

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.2072C>A (p.Ser691Ter)

HGVS:

NC_000019.10:g.11120454C>A
NG_009060.1:g.36074C>A
NM_000527.5:c.2072C>AMANE SELECT
NM_001195798.2:c.2072C>A
NM_001195799.2:c.1949C>A
NM_001195800.2:c.1568C>A
NM_001195803.2:c.1606+221C>A
NP_000518.1:p.Ser691Ter
NP_000518.1:p.Ser691Ter
NP_001182727.1:p.Ser691Ter
NP_001182728.1:p.Ser650Ter
NP_001182729.1:p.Ser523Ter
LRG_274t1:c.2072C>A
LRG_274:g.36074C>A
LRG_274p1:p.Ser691Ter
NC_000019.9:g.11231130C>A
NM_000527.4:c.2072C>A
c.2072C>A

Protein change:

S523*

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001597; dbSNP: rs369943481

NCBI 1000 Genomes Browser:

rs369943481

Molecular consequence:

NM_001195803.2:c.1606+221C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.2072C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195798.2:c.2072C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195799.2:c.1949C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195800.2:c.1568C>A - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000295858	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,
SCV000540855	Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation See additional submitters Centre of Molecular Biology and Gene Therapy, University Hospital Brno	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 5, 2016)	inherited	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

SCV000295858

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,

SCV000540855

Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 5, 2016)

inherited

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	1	not provided	not provided	1	not provided	literature only
Caucasian	inherited	yes	2	1	not provided	3964	yes	clinical testing

Citations

PubMed

Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy.

Bertolini S, Pisciotta L, Rabacchi C, Cefalù AB, Noto D, Fasano T, Signori A, Fresa R, Averna M, Calandra S.

Atherosclerosis. 2013 Apr;227(2):342-8. doi: 10.1016/j.atherosclerosis.2013.01.007. Epub 2013 Jan 19.

PubMed [citation]

PMID:: 23375686

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, SCV000295858.2

#	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 Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation, SCV000540855.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasian	2	not provided	yes	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	3964	Whole blood	not provided		2	not provided	1	not provided

Last Updated: May 1, 2024

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