ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1633G>A (p.Gly545Arg) (rs879254965)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000238474 SCV000295546 likely pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter research
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000238474 SCV000503378 likely pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 3(1 compound heterozygote) , family members = 2 with co-segregation/Software predictions: Conflicting
Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation RCV000238474 SCV000540831 pathogenic Familial hypercholesterolemia 1 2016-11-05 criteria provided, single submitter clinical testing
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000238474 SCV000583856 pathogenic Familial hypercholesterolemia 1 2017-03-30 criteria provided, single submitter clinical testing
Invitae RCV001321570 SCV001512406 uncertain significance Familial hypercholesterolemia 2020-07-16 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 545 of the LDLR protein (p.Gly545Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of familial hypercholesterolemia (PMID: 20809525, 26343872, Invitae). ClinVar contains an entry for this variant (Variation ID: 251942). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). This variant disrupts the p.Gly545 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been observed in individuals with LDLR-related conditions (PMID: 23535506, 26020417), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000238474 SCV000606471 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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