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NM_000527.5(LDLR):c.1747C>T (p.His583Tyr) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 1, 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:
RCV002399654.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1747C>T (p.His583Tyr)]

NM_000527.5(LDLR):c.1747C>T (p.His583Tyr)

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.1747C>T (p.His583Tyr)
Other names:
p.H583Y:CAC>TAC; NP_000518.1:p.H583Y
HGVS:
  • NC_000019.10:g.11116900C>T
  • NG_009060.1:g.32520C>T
  • NM_000527.5:c.1747C>TMANE SELECT
  • NM_001195798.2:c.1747C>T
  • NM_001195799.2:c.1624C>T
  • NM_001195800.2:c.1243C>T
  • NM_001195803.2:c.1366C>T
  • NP_000518.1:p.His583Tyr
  • NP_000518.1:p.His583Tyr
  • NP_001182727.1:p.His583Tyr
  • NP_001182728.1:p.His542Tyr
  • NP_001182729.1:p.His415Tyr
  • NP_001182732.1:p.His456Tyr
  • LRG_274t1:c.1747C>T
  • LRG_274:g.32520C>T
  • LRG_274p1:p.His583Tyr
  • NC_000019.9:g.11227576C>T
  • NM_000527.4:c.1747C>T
  • c.1747C>T
Protein change:
H415Y
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000234; dbSNP: rs730882109
NCBI 1000 Genomes Browser:
rs730882109
Molecular consequence:
  • NM_000527.5:c.1747C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1747C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1624C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1243C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1366C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

Recent activity

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  • RecName: Full=Bis(monoacylglycero)phosphate synthase CLN5; Short=BMP synthase CL...
    RecName: Full=Bis(monoacylglycero)phosphate synthase CLN5; Short=BMP synthase CLN5; AltName: Full=Ceroid-lipofuscinosis neuronal protein 5; Short=Protein CLN5; AltName: Full=Palmitoyl protein thioesterase CLN5; AltName: Full=S-depalmitoylase CLN5; Contains: RecName: Full=Bis(monoacylglycero)phosphate synthase CLN5, secreted form
    gi|187608866|sp|O75503.2|CLN5_HUMAN
    Protein

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002711608Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 1, 2021) 		germlineclinical testing

PubMed (9)
[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

Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform.

Alonso R, Defesche JC, Tejedor D, Castillo S, Stef M, Mata N, Gomez-Enterria P, Martinez-Faedo C, Forga L, Mata P.

Clin Biochem. 2009 Jun;42(9):899-903. doi: 10.1016/j.clinbiochem.2009.01.017. Epub 2009 Feb 6.

PubMed [citation]
PMID:
19318025

Common mutations of familial hypercholesterolemia patients in Taiwan: characteristics and implications of migrations from southeast China.

Chiou KR, Charng MJ.

Gene. 2012 Apr 25;498(1):100-6. doi: 10.1016/j.gene.2012.01.092. Epub 2012 Feb 14.

PubMed [citation]
PMID:
22353362
See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV002711608.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

The p.H583Y pathogenic mutation (also known as c.1747C>T and p.H562Y), located in coding exon 12 of the LDLR gene, results from a C to T substitution at nucleotide position 1747. The histidine at codon 583 is replaced by tyrosine, an amino acid with similar properties. This mutation has been described as a Chinese founder mutation and has been reported in multiple individuals, as well as affected family members, with familial hypercholesterolemia (FH). (Sun XM et al, Arterioscler. Thromb. 1994 Jan; 14(1):85-94; Yao RE et al, J. Pediatr. Endocrinol. Metab. 2012 ; 25(7-8):769-73; Chiou KR et al, Gene 2012 Apr; 498(1):100-6; Hooper AJ et al, Atherosclerosis 2012 Oct; 224(2):430-4; Fan LL et al, Appl. Biochem. Biotechnol. 2015 May; 176(1):101-9; Ma Y et al. J Clin Lipidol Oct;12:230-235.e6). This variant has also been confirmed in trans with a second LDLR mutation in an individual with homozygous FH (Chiou KR et al, Gene 2012 Apr; 498(1):100-6). Alterations at the same amino acid position, including p.H583D (Bertolini S et al, Atherosclerosis 2013 Apr; 227(2):342-8), p.H583Q (Alonso R et al, Clin. Biochem. 2009 Jun; 42(9):899-903) and p.H583R (Tichý L et al, Atherosclerosis 2012 Aug; 223(2):401-8) have also been reported in FH patients. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Jun 23, 2024