ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1646G>A (p.Gly549Asp) (rs28941776)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000003886 SCV000503381 likely pathogenic Familial hypercholesterolemia 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 4 , family member = 1 with co-segregation / FH-Palermo, 2% LDLR activity / Software predictions: Damaging
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000161997 SCV000189572 not provided not provided no assertion provided in vitro
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000003886 SCV000733824 pathogenic Familial hypercholesterolemia no assertion criteria provided clinical testing
Fulgent Genetics,Fulgent Genetics RCV000003886 SCV000894176 pathogenic Familial hypercholesterolemia 2018-10-31 criteria provided, single submitter clinical testing
Fundacion Hipercolesterolemia Familiar RCV000003886 SCV000607619 likely pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
Iberoamerican FH Network RCV000003886 SCV000748175 likely pathogenic Familial hypercholesterolemia 2016-03-01 no assertion criteria provided research
Integrated Genetics/Laboratory Corporation of America RCV000587938 SCV000697207 pathogenic Familial hypercholesterolemias 2017-03-17 criteria provided, single submitter clinical testing
Invitae RCV000587938 SCV000544685 pathogenic Familial hypercholesterolemias 2018-08-11 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 549 of the LDLR protein (p.Gly549Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs28941776, ExAC 0.009%). This variant is clearly defined as a familial hypercholesterolemia causative allele (PMID: 23375686, 25487149). It is a common cause of familial hypercholesterolemia in individuals of Italian ancestry. This variant is also known as p.Glu528Asp in the literature. ClinVar contains an entry for this variant (Variation ID: 3698). Experimental studies have shown that this missense change inhibits the transport of the LDLR protein to the cellular surface (PMID: 25647241). For these reasons, this variant has been classified as Pathogenic.
LDLR-LOVD, British Heart Foundation RCV000003886 SCV000295560 likely pathogenic Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000003886 SCV000606474 pathogenic Familial hypercholesterolemia no assertion criteria provided research
Laboratory of Genetics and Molecular Cardiology,University of São Paulo RCV000003886 SCV000588600 likely pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation RCV000003886 SCV000540828 likely pathogenic Familial hypercholesterolemia 2016-11-05 criteria provided, single submitter clinical testing
OMIM RCV000003886 SCV000024051 pathogenic Familial hypercholesterolemia 1988-11-01 no assertion criteria provided literature only
Robarts Research Institute,Western University RCV000003886 SCV000484682 likely pathogenic Familial hypercholesterolemia criteria provided, single submitter clinical testing
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000003886 SCV000583858 pathogenic Familial hypercholesterolemia 2017-03-30 criteria provided, single submitter clinical testing

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