ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1166C>T (p.Thr389Met) (rs149227308)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237987 SCV000295252 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 RCV000237987 SCV000503307 uncertain significance Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1 / Software predictions: Conflicting
Color Health, Inc RCV001181606 SCV001346785 uncertain significance Familial hypercholesterolemia 2020-01-15 criteria provided, single submitter clinical testing
Invitae RCV001181606 SCV001538685 uncertain significance Familial hypercholesterolemia 2020-03-14 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 389 of the LDLR protein (p.Thr389Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs149227308, ExAC 0.01%). This variant has been observed in individual(s) with clinical features of familial hypercholesterolemia (PMID: 17196209, 23375686, Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 161283). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). 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. 5
CSER _CC_NCGL, University of Washington RCV000148590 SCV000190304 uncertain significance Hypercholesterolaemia 2014-06-01 no assertion criteria provided research
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000237987 SCV000606340 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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