NM_000527.5(LDLR):c.97C>T (p.Gln33Ter) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 21, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002381238.2

Allele description [Variation Report for NM_000527.5(LDLR):c.97C>T (p.Gln33Ter)]

NM_000527.5(LDLR):c.97C>T (p.Gln33Ter)

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.97C>T (p.Gln33Ter)

Other names:

Q12*; FH Turkey; FH Turkey/Milan-4; NM_000527.5(LDLR):c.97C>T; p.Gln33Ter

HGVS:

NC_000019.10:g.11100252C>T
NG_009060.1:g.15872C>T
NM_000527.5:c.97C>TMANE SELECT
NM_001195798.2:c.97C>T
NM_001195799.2:c.97C>T
NM_001195800.2:c.97C>T
NM_001195803.2:c.97C>T
NP_000518.1:p.Gln33Ter
NP_000518.1:p.Gln33Ter
NP_001182727.1:p.Gln33Ter
NP_001182728.1:p.Gln33Ter
NP_001182729.1:p.Gln33Ter
NP_001182732.1:p.Gln33Ter
LRG_274t1:c.97C>T
LRG_274:g.15872C>T
LRG_274p1:p.Gln33Ter
NC_000019.9:g.11210928C>T
NM_000527.4:c.97C>T
NM_000527.5:c.97C>T
c.97C>T
p.(Gln33*)
p.Gln33*

Protein change:

Q33*; GLN12TER

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001896; OMIM: 606945.0001

Molecular consequence:

NM_000527.5:c.97C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001195798.2:c.97C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001195799.2:c.97C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001195800.2:c.97C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001195803.2:c.97C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Gene ID:108306371

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002694005	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 21, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 1301940, 15241806, 16250003, 2088165, 23375686, 24088637 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002694005

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 21, 2022)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Screening for new mutations in the LDL receptor gene in seven French familial hypercholesterolemia families by the single strand conformation polymorphism method.

Loux N, Saint-Jore B, Collod G, Dairou F, Benlian P, Truffert J, Dastugue B, Douste-Blazy P, de Gennes JL, Junien C, et al.

Hum Mutat. 1992;1(4):325-32.

PubMed [citation]

PMID:: 1301940

Molecular characterization of familial hypercholesterolemia in Spain: identification of 39 novel and 77 recurrent mutations in LDLR.

Mozas P, Castillo S, Tejedor D, Reyes G, Alonso R, Franco M, Saenz P, Fuentes F, Almagro F, Mata P, Pocoví M.

Hum Mutat. 2004 Aug;24(2):187.

PubMed [citation]

PMID:: 15241806

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002694005.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The p.Q33* pathogenic mutation (also known as c.97C>T), located in coding exon 2 of the LDLR gene, results from a C to T substitution at nucleotide position 97. This changes the amino acid from a glutamine to a stop codon within coding exon 2. This alteration has been reported in association with familial hypercholesterolemia across various ethnicities (also reported as p.Q12X) (Hobbs HH, Annu. Rev. Genet. 1990 ; 24:133-70; Mozas P, Hum. Mutat. 2004 Aug; 24(2):187; Zakharova FM, BMC Med. Genet. 2005 Feb;6:6; Fouchier SW, Hum. Mutat. 2005 Dec; 26(6):550-6). This alteration was also reported in a homozygous state in two individuals who both had total cholesterol levels greater than 600 mg/dl (Loux N, Hum. Mutat. 1992;1(4):325-32; Meng X, Indian J Ophthalmol 2013 Dec; 61(12):770-1). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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

Last Updated: Sep 29, 2024

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