ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1694G>T (p.Gly565Val) (rs28942082)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000003874 SCV000295584 likely pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000003874 SCV000503387 pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 6 , family members = 2 with co-segregation / Functional test, FH-Naples-2, 2% LDLR Activity, Other mutations at same codon / Software predictions: Damaging
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000003874 SCV000583865 pathogenic Familial hypercholesterolemia 1 2017-03-30 criteria provided, single submitter clinical testing
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000003874 SCV000599379 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter curation
Invitae RCV000791454 SCV000752407 pathogenic Familial hypercholesterolemia 2018-10-08 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 565 of the LDLR protein (p.Gly565Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in both the homozygous and heterozygous state in several individuals affected with familial hypercholesterolemia (PMID: 2901412, 23375686, 12436241). This variant is also described in the literature as p.Gly544Val. ClinVar contains an entry for this variant (Variation ID: 3688). Experimental studies have shown that this missense change disrupts transport of LDL-receptor to the Golgi apparatus, resulting in a cell surface that lacks LDL-receptors (PMID: 2901412, 16740646). Variants that disrupt the p.Gly565 amino acid residue in LDLR have been observed in affected individuals (PMID: 27784735, 11313767). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000003874 SCV000024039 pathogenic Familial hypercholesterolemia 1 1988-09-15 no assertion criteria provided literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000003874 SCV000606487 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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