NM_000527.5(LDLR):c.1247G>A (p.Arg416Gln) AND not provided

Clinical significance:Pathogenic (Last evaluated: Dec 13, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000437123.1

Allele description [Variation Report for NM_000527.5(LDLR):c.1247G>A (p.Arg416Gln)]

NM_000527.5(LDLR):c.1247G>A (p.Arg416Gln)

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.1247G>A (p.Arg416Gln)
HGVS:
  • NC_000019.10:g.11113338G>A
  • NG_009060.1:g.28958G>A
  • NM_000527.4:c.1247G>A
  • NM_000527.5:c.1247G>AMANE SELECT
  • NM_001195798.2:c.1247G>A
  • NM_001195799.2:c.1124G>A
  • NM_001195800.2:c.743G>A
  • NM_001195803.2:c.866G>A
  • NP_000518.1:p.Arg416Gln
  • NP_000518.1:p.Arg416Gln
  • NP_001182727.1:p.Arg416Gln
  • NP_001182728.1:p.Arg375Gln
  • NP_001182729.1:p.Arg248Gln
  • NP_001182732.1:p.Arg289Gln
  • LRG_274t1:c.1247G>A
  • LRG_274:g.28958G>A
  • NC_000019.9:g.11224014G>A
  • NM_000527.4(LDLR):c.1247G>A
  • P01130:p.Arg416Gln
  • c.1247G>A
Protein change:
R248Q
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000379; UniProtKB: P01130#VAR_005380; dbSNP: rs773658037
NCBI 1000 Genomes Browser:
rs773658037
Molecular consequence:
  • NM_000527.4:c.1247G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000527.5:c.1247G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1247G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1124G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.743G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.866G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000520999GeneDxcriteria provided, single submitter
Pathogenic
(Dec 13, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000520999.3

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

Description

The R416Q variant in the LDLR gene has been reported previously in association with familial hypercholesterolemia (Thiart et al., 1998; Fouchier et al., 2001; Hollants et al., 2012; Huijgen et al., 2012). The R416Q variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R416Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in the same codon (R416W, R416P, R416L) have been reported in the Human Gene Mutation Database in association with familial hypercholesterolemia (Stenson et al., 2014), supporting the functional importance of this codon. We interpret R416Q as a pathogenic variant

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

Last Updated: May 23, 2021

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