U.S. flag

An official website of the United States government

NM_000527.5(LDLR):c.1721G>A (p.Arg574His) AND LDLR-related disorder

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 13, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV003401206.5

Allele description [Variation Report for NM_000527.5(LDLR):c.1721G>A (p.Arg574His)]

NM_000527.5(LDLR):c.1721G>A (p.Arg574His)

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.1721G>A (p.Arg574His)
Other names:
NM_000527.5(LDLR):c.1721G>A
HGVS:
  • NC_000019.10:g.11116874G>A
  • NG_009060.1:g.32494G>A
  • NM_000527.5:c.1721G>AMANE SELECT
  • NM_001195798.2:c.1721G>A
  • NM_001195799.2:c.1598G>A
  • NM_001195800.2:c.1217G>A
  • NM_001195803.2:c.1340G>A
  • NP_000518.1:p.Arg574His
  • NP_000518.1:p.Arg574His
  • NP_001182727.1:p.Arg574His
  • NP_001182728.1:p.Arg533His
  • NP_001182729.1:p.Arg406His
  • NP_001182732.1:p.Arg447His
  • LRG_274t1:c.1721G>A
  • LRG_274:g.32494G>A
  • LRG_274p1:p.Arg574His
  • NC_000019.9:g.11227550G>A
  • NM_000527.4:c.1721G>A
  • P01130:p.Arg574His
  • c.1721G>A
Protein change:
R406H
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000233; UniProtKB: P01130#VAR_072852
Molecular consequence:
  • NM_000527.5:c.1721G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1721G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1598G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1217G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1340G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
LDLR-related disorder
Synonyms:
LDLR-related condition
Identifiers:

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
SCV004119517PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Likely pathogenic
(Jun 13, 2024) 		germlineclinical testing

Help

Summary from all submissions

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004119517.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The LDLR c.1721G>A variant is predicted to result in the amino acid substitution p.Arg574His. This variant has been observed in multiple individuals affected with familial hypercholesterolemia and segregated with disease in at least one family (see, for example, Pisciotta et al. 2010. PubMed ID: 20018285, Jannes et al. 2015. PubMed ID: 25461735, Bertolini et al. 2013. PubMed ID: 23375686). This variant is reported in 0.011% of alleles in individuals of Latino descent in gnomAD. This variant has been classified as likely pathogenic by the ClinGen Familial Hypercholesterolemia Expert Panel (Clinvar ID: 251996). We interpret this variant as likely pathogenic.

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

Last Updated: Oct 20, 2024