ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1816G>T (p.Ala606Ser) (rs72658865)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER_CC_NCGL; University of Washington Medical Center 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 2012-08-07 no assertion criteria provided clinical testing
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000211562 SCV000322977 uncertain significance Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research 0/220 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 RCV000211562 SCV000503417 uncertain significance Familial hypercholesterolemia 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
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000162003 SCV000189578 not provided not provided no assertion provided in vitro
Invitae RCV000791434 SCV000627022 uncertain significance Familial hypercholesterolemias 2018-09-13 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.
LDLR-LOVD, British Heart Foundation RCV000211562 SCV000295675 uncertain significance Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000211562 SCV000606521 benign Familial hypercholesterolemia no assertion criteria provided research
Robarts Research Institute,Western University RCV000211562 SCV000484684 uncertain significance Familial hypercholesterolemia 2019-08-22 criteria provided, single submitter clinical testing

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