U.S. flag

An official website of the United States government

NM_000527.5(LDLR):c.2029T>C (p.Cys677Arg) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 15, 2021
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:
RCV002415889.2

Allele description [Variation Report for NM_000527.5(LDLR):c.2029T>C (p.Cys677Arg)]

NM_000527.5(LDLR):c.2029T>C (p.Cys677Arg)

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.2029T>C (p.Cys677Arg)
Other names:
FH New York-3; NP_000518.1:p.C677R
HGVS:
  • NC_000019.10:g.11120411T>C
  • NG_009060.1:g.36031T>C
  • NM_000527.5:c.2029T>CMANE SELECT
  • NM_001195798.2:c.2029T>C
  • NM_001195799.2:c.1906T>C
  • NM_001195800.2:c.1525T>C
  • NM_001195803.2:c.1606+178T>C
  • NP_000518.1:p.Cys677Arg
  • NP_000518.1:p.Cys677Arg
  • NP_001182727.1:p.Cys677Arg
  • NP_001182728.1:p.Cys636Arg
  • NP_001182729.1:p.Cys509Arg
  • LRG_274t1:c.2029T>C
  • LRG_274:g.36031T>C
  • LRG_274p1:p.Cys677Arg
  • NC_000019.9:g.11231087T>C
  • NM_000527.4:c.2029T>C
  • P01130:p.Cys677Arg
  • c.2029T>C
Protein change:
C509R
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001587; UniProtKB: P01130#VAR_005408; dbSNP: rs775092314
NCBI 1000 Genomes Browser:
rs775092314
Molecular consequence:
  • NM_001195803.2:c.1606+178T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.2029T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.2029T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1906T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1525T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002718691Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 15, 2021) 		germlineclinical testing

PubMed (8)
[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 genetics of the LDL receptor gene in familial hypercholesterolemia.

Hobbs HH, Brown MS, Goldstein JL.

Hum Mutat. 1992;1(6):445-66. Review.

PubMed [citation]
PMID:
1301956

Mutational analysis in UK patients with a clinical diagnosis of familial hypercholesterolaemia: relationship with plasma lipid traits, heart disease risk and utility in relative tracing.

Humphries SE, Cranston T, Allen M, Middleton-Price H, Fernandez MC, Senior V, Hawe E, Iversen A, Wray R, Crook MA, Wierzbicki AS.

J Mol Med (Berl). 2006 Mar;84(3):203-14. Epub 2005 Dec 31.

PubMed [citation]
PMID:
16389549
See all PubMed Citations (8)

Details of each submission

From Ambry Genetics, SCV002718691.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

The p.C677R pathogenic mutation (also known as c.2029T>C), located in coding exon 14 of the LDLR gene, results from a T to C substitution at nucleotide position 2029. The cysteine at codon 677 is replaced by arginine, an amino acid with highly dissimilar properties. This alteration was detected in conjunction with another alteration in the LDLR gene in an individual whose protein activity was 5-15% of normal (Hobbs HH et al. Hum Mutat. 1992;1(6):445-66). Subsequent studies observed this alteration in several individuals diagnosed with familial hypercholesterolemia (FH) (Humphries SE et al. J Mol Med. 2006; 84(3):203-14; Tosi I et al. Atherosclerosis. 2007;194(1):102-11). In a case report, this alteration was described to co-segregate with FH in multiple individuals in one family (Bima AI et al. Ann Clin Biochem. 2009;46(Pt 5):420-2). Another alteration affecting the same codon (p.C677Y c.2030G>A) has also been described in patients with FH (Salazar LA et al. Hum Mutat. 2002;19(4):462-3). Based on the supporting evidence, p.C677R 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