U.S. flag

An official website of the United States government

NM_000527.5(LDLR):c.2029T>C (p.Cys677Arg) AND Homozygous familial hypercholesterolemia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 11, 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:
RCV004017508.1

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:
Homozygous familial hypercholesterolemia
Synonyms:
Familial hypercholesterolemia - homozygous
Identifiers:
MONDO: MONDO:0018328; MedGen: C0342881

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
SCV004847793Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely Pathogenic
(Oct 11, 2019) 		germlineclinical testing

PubMed (12)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in the low-density lipoprotein receptor gene in Chinese familial hypercholesterolemia patients.

Mak YT, Pang CP, Tomlinson B, Zhang J, Chan YS, Mak TW, Masarei JR.

Arterioscler Thromb Vasc Biol. 1998 Oct;18(10):1600-5.

PubMed [citation]
PMID:
9763532

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
See all PubMed Citations (12)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847793.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (12)

Description

The p.Cys677Arg variant in LDLR has been reported in at least 7 individuals with hypercholesterolemia and segregated with disease in 6 affected individuals from 1 family (Hobbs 1992, Heath 1999, Humphries 2006, Bima 2009, Hooper 2012, Martin 2016, Wang 2016). It has also been identified in 1/113610 of European chromosomes by gnomAD (http://gnomad.broadinstitute.org) and has been reported in ClinVar (Variation ID 226384). An in vitro functional study and computational prediction tools support an impact on protein function (Hobbs 1992). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant familial . ACMG/AMP Criteria applied: PM2, PS4_Moderate, PP1_Moderate, PP3, PS3_Supporting.

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

Last Updated: Sep 29, 2024