ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1816G>T (p.Ala606Ser) (rs72658865)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000211562 SCV000295675 uncertain significance Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000211562 SCV000322977 uncertain significance Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research 0/220 non-FH alleles
Robarts Research Institute,Western University RCV000211562 SCV000484684 uncertain significance Familial hypercholesterolemia 1 2019-08-22 criteria provided, single submitter clinical testing
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000211562 SCV000503417 uncertain significance Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 3 / previously described in association with FH/Software predictions: Conflicting
Invitae RCV000791434 SCV000627022 uncertain significance Familial hypercholesterolemia 2019-10-18 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 606 of the LDLR protein (p.Ala606Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs72658865, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in many individuals with possible or definite familial hypercholesterolemia (PMID: 9409298, 9544745, 14974088, 15199436, 16250003, 17765246, 18325082, 24956927, 27765764). This variant is also known as p.Arg585Ser in the literature. ClinVar contains an entry for this variant (Variation ID: 161264). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Color Health, Inc RCV000791434 SCV001347963 uncertain significance Familial hypercholesterolemia 2020-06-24 criteria provided, single submitter clinical testing This missense variant (also known as p.Ala585Ser in the mature protein) replaces alanine with serine at codon 606 of the LDLR protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Experimental studies have shown that this variant has neutral LDLR expression, LDLR binding and LDL uptake activity compared to wildtype, suggesting this variant may not disrupt LDLR function (PMID: 25647241, 32015373). This variant has been reported in multiple individuals affected with familial hypercholesterolemia (PMID: 9409298, 9544745, 14974088, 15199436, 16250003, 17765246, 18325082, 25647241, 27765764). This variant has been identified in 31/282830 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Brunham Lab, Centre for Heart and Lung Innovation,University of British Columbia RCV000211562 SCV001432594 uncertain significance Familial hypercholesterolemia 1 2019-06-17 criteria provided, single submitter research
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000162003 SCV000189578 not provided not provided no assertion provided in vitro
CSER _CC_NCGL, University of Washington RCV000148567 SCV000190280 likely pathogenic Hypercholesterolaemia 2014-06-01 no assertion criteria provided research
Cardiovascular Genetics Laboratory,PathWest Laboratory Medicine WA - Fiona Stanley Hospital RCV000211562 SCV000268641 uncertain significance Familial hypercholesterolemia 1 2012-08-07 no assertion criteria provided clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000211562 SCV000606521 benign Familial hypercholesterolemia 1 no assertion criteria provided research
Natera, Inc. RCV000791434 SCV001461320 uncertain significance Familial hypercholesterolemia 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.