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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 31, 2019
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:: RCV002418069.2

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]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002726343	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (May 31, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23375686, 30592178 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002726343

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(May 31, 2019)

germline

clinical testing

PubMed (2)
[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

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

Genetic variations in familial hypercholesterolemia and cascade screening in East Asians.

Chan ML, Cheung CL, Lee AC, Yeung CY, Siu CW, Leung JY, Pang HK, Tan KC.

Mol Genet Genomic Med. 2019 Feb;7(2):e00520. doi: 10.1002/mgg3.520. Epub 2018 Dec 27.

PubMed [citation]

PMID:: 30592178
PMCID:: PMC6393658

Details of each submission

From Ambry Genetics, SCV002726343.2

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

Description

The p.S691* pathogenic mutation (also known as c.2072C>A), located in coding exon 14 of the LDLR gene, results from a C to A substitution at nucleotide position 2072. This changes the amino acid from a serine to a stop codon within coding exon 14. This mutation has been detected in familial hypercholesterolemia cohorts (Bertolini S et al. Atherosclerosis, 2013 Apr;227:342-8; Chan ML et al. Mol Genet Genomic Med, 2019 02;7:e00520). 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: May 1, 2024

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