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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002726343Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(May 31, 2019) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024