ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.806G>A (p.Gly269Asp) (rs143992984)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cardiovascular Biomarker Research Laboratory,Mayo Clinic RCV000210247 SCV000266316 likely benign Familial hypercholesterolemia 1 2015-08-31 criteria provided, single submitter research MAF =<0.3%. "Little/No effect" on the LDL receptor activity based on experimental validation.
LDLR-LOVD, British Heart Foundation RCV000210247 SCV000294983 likely benign Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000210247 SCV000322915 likely benign Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research 0/212 non-FH alleles
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000210247 SCV000503239 likely benign Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 3 / FH-Rome-3 / Software predictions: Conflicting
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000210247 SCV000583743 likely pathogenic Familial hypercholesterolemia 1 2017-03-30 criteria provided, single submitter clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000210247 SCV000588518 likely benign Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Fundacion Hipercolesterolemia Familiar RCV000210247 SCV000607503 likely benign Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Integrated Genetics/Laboratory Corporation of America RCV000161966 SCV000697252 benign not provided 2016-03-11 criteria provided, single submitter clinical testing Variant summary: c.806G>A affects a non-conserved nucleotide, resulting in amino acid change from Gly to Asp. 2/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). Functional study showed that the LDL uptake, binding capacity of LDL, and LDLR expression of variant were similar to those observed in control cells (Etxebarria_2012), indicating the neutral effect. This variant was found in 24/131566 control chromosomes at a frequency of 0.0001824. This variant has been reported in multiple FH patients without strong evidence for causality. Among the reported patients, variant was reported to co-occur with a deleterious LDLR variant c.1045delC in cis (Mozas_2004) and there is at least one family reported with lack of co-segregation of this variant with disease (Bourbon_2008). In addition, variant has been detected in early-onset myocardial infarction case with comparable allele frequency as in controls and multiple publications listed variant as nonpathogenic/benign (Do_2015, Etxebarre_2012, and Benito-Vicente_2015). Considering all, this variant is classified as Benign.
Invitae RCV000775049 SCV000752451 likely benign Familial hypercholesterolemia 2019-12-31 criteria provided, single submitter clinical testing
Color RCV000775049 SCV000909148 likely benign Familial hypercholesterolemia 2018-07-10 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000210247 SCV001282942 uncertain significance Familial hypercholesterolemia 1 2018-03-08 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000161966 SCV000189541 not provided not provided no assertion provided in vitro
CSER _CC_NCGL, University of Washington RCV000148586 SCV000190300 uncertain significance Hypercholesterolaemia 2014-06-01 no assertion criteria provided research
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000210247 SCV000606229 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research
Iberoamerican FH Network RCV000210247 SCV000748174 likely benign Familial hypercholesterolemia 1 2016-03-01 no assertion criteria provided research

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