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NM_000527.5(LDLR):c.693C>A (p.Cys231Ter) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 8, 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:
RCV002362558.9

Allele description [Variation Report for NM_000527.5(LDLR):c.693C>A (p.Cys231Ter)]

NM_000527.5(LDLR):c.693C>A (p.Cys231Ter)

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.693C>A (p.Cys231Ter)
Other names:
C210*; FH London 3; NP_000518.1:p.C231*
HGVS:
  • NC_000019.10:g.11105599C>A
  • NG_009060.1:g.21219C>A
  • NM_000527.5:c.693C>AMANE SELECT
  • NM_001195798.2:c.693C>A
  • NM_001195799.2:c.570C>A
  • NM_001195800.2:c.314-1793C>A
  • NM_001195803.2:c.314-966C>A
  • NP_000518.1:p.Cys231Ter
  • NP_000518.1:p.Cys231Ter
  • NP_001182727.1:p.Cys231Ter
  • NP_001182728.1:p.Cys190Ter
  • LRG_274t1:c.693C>A
  • LRG_274:g.21219C>A
  • LRG_274p1:p.Cys231Ter
  • NC_000019.9:g.11216275C>A
  • NM_000527.4:c.693C>A
  • c.693C>A
  • p.Cys231*
Protein change:
C190*; CYS210TER
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000109; OMIM: 606945.0048
Molecular consequence:
  • NM_001195800.2:c.314-1793C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195803.2:c.314-966C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.693C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001195798.2:c.693C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001195799.2:c.570C>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
SCV002664339Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Sep 8, 2022) 		germlineclinical testing

PubMed (3)
[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

Molecular characterization of Polish patients with familial hypercholesterolemia: novel and recurrent LDLR mutations.

Chmara M, Wasag B, Zuk M, Kubalska J, Wegrzyn A, Bednarska-Makaruk M, Pronicka E, Wehr H, Defesche JC, Rynkiewicz A, Limon J.

J Appl Genet. 2010;51(1):95-106. doi: 10.1007/BF03195716.

PubMed [citation]
PMID:
20145306

An APEX-based genotyping microarray for the screening of 168 mutations associated with familial hypercholesterolemia.

Dušková L, Kopečková L, Jansová E, Tichý L, Freiberger T, Zapletalová P, Soška V, Ravčuková B, Fajkusová L.

Atherosclerosis. 2011 May;216(1):139-45. doi: 10.1016/j.atherosclerosis.2011.01.023. Epub 2011 Jan 21.

PubMed [citation]
PMID:
21310417
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002664339.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The p.C231* pathogenic mutation (also known as c.693C>A), located in coding exon 4 of the LDLR gene, results from a C to A substitution at nucleotide position 693. This changes the amino acid from a cysteine to a stop codon within coding exon 4. This alteration (also described as p.C210*) has been reported in familial hypercholesterolemia cohorts (Gudnason V et al. Arterioscler. Thromb., 1993 Jan;13:56-63; Chmara M et al. J. Appl. Genet., 2010;51:95-106; Dušková L et al. Atherosclerosis, 2011 May;216:139-45). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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: Sep 29, 2024