ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1765G>A (p.Asp589Asn) (rs201971888)

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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 RCV000237292 SCV000295644 uncertain significance 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 RCV000237292 SCV000503409 uncertain significance Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 2 / in association with c.769C>T, p.Arg257Trp/Software predictions: Benign
Invitae RCV000775077 SCV000544660 uncertain significance Familial hypercholesterolemia 2019-12-20 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 589 of the LDLR protein (p.Asp589Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs201971888, ExAC 0.08%). This variant has been observed in several individuals affected with familial hypercholesterolemia (PMID: 16250003, 25962062, 22353362, 20538126, 26343872, 27206935, 29399563, 28502495, 29353225). This variant is also known as p.Asp568Asn in the literature. ClinVar contains an entry for this variant (Variation ID: 252022). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. 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.
Robarts Research Institute,Western University RCV000237292 SCV000782927 uncertain significance Familial hypercholesterolemia 1 2018-01-02 criteria provided, single submitter clinical testing
Color RCV000775077 SCV000909179 uncertain significance Familial hypercholesterolemia 2019-07-09 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845536 SCV000987650 uncertain significance not provided criteria provided, single submitter clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000237292 SCV000606508 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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