ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1118G>A (p.Gly373Asp) (rs879254797)

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Total submissions: 8
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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 RCV000237895 SCV000503300 likely pathogenic Familial hypercholesterolemia 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 3 / FH-Potenza-2 / Software predictions: Damaging
Fundacion Hipercolesterolemia Familiar RCV000237895 SCV000607560 likely pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
Iberoamerican FH Network RCV000237895 SCV000748096 likely pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
Invitae RCV000791447 SCV000825010 pathogenic Familial hypercholesterolemias 2018-12-20 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 373 of the LDLR protein (p.Gly373Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with familial hypercholesterolemia (PMID: 9974426, 25461735, 11933210, 21382890, 23375686, 15241806, 11810272). This variant is also known as p.Gly352Asp in the literature. ClinVar contains an entry for this variant (Variation ID: 251673). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Other missense substitutions at this codon (p.Gly373Val and p.Gly373Cys) have been reported in individuals affected with familial hypercholesterolemia (PMID: 16159606, 20145306). For these reasons, this variant has been classified as Pathogenic.
LDLR-LOVD, British Heart Foundation RCV000237895 SCV000295229 likely pathogenic Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000237895 SCV000606332 pathogenic Familial hypercholesterolemia no assertion criteria provided research
Laboratory of Genetics and Molecular Cardiology,University of São Paulo RCV000237895 SCV000588555 likely pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000237895 SCV000583791 pathogenic Familial hypercholesterolemia 2017-03-30 criteria provided, single submitter clinical testing

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