ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.683A>G (p.Glu228Gly)

dbSNP: rs879254642
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Total submissions: 4
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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 RCV000417331 SCV000503222 likely pathogenic Hypercholesterolemia, familial, 1 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1 , family member = 1 with co-segregation / other mutation at same codon / Software predictions: Damaging
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000417331 SCV000583727 pathogenic Hypercholesterolemia, familial, 1 2017-03-30 criteria provided, single submitter clinical testing
Invitae RCV003766177 SCV004630979 pathogenic Familial hypercholesterolemia 2023-11-15 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 228 of the LDLR protein (p.Glu228Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of LDLR-related conditions (PMID: 31491741; Invitae). ClinVar contains an entry for this variant (Variation ID: 375796). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LDLR protein function with a positive predictive value of 95%. This variant disrupts the p.Glu228 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1301956, 2318961, 8882879, 16250003, 17094996, 21475731, 21722902, 22390909, 23375686). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000417331 SCV000606204 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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