ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2140G>T (p.Glu714Ter) (rs869320652)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SNPedia RCV000210844 SCV000267120 likely pathogenic Familial hypercholesterolemia 1 2016-04-03 criteria provided, single submitter literature only
LDLR-LOVD, British Heart Foundation RCV000210844 SCV000295890 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 RCV000210844 SCV000503468 pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 5 , family members = 5
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000210844 SCV000583930 pathogenic Familial hypercholesterolemia 1 2017-03-30 criteria provided, single submitter clinical testing
GeneDx RCV000523095 SCV000617496 pathogenic not provided 2017-09-01 criteria provided, single submitter clinical testing The E714X variant in the LDLR gene has been reported in association with FH (Amsellam et al., 2002; Khera et al., 2016). The E714X variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the LDLR gene have been reported in Human Gene Mutation Database in association with FH (Stenson et al., 2014). Furthermore, the E714X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Invitae RCV000210844 SCV000752420 pathogenic Familial hypercholesterolemia 1 2017-08-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu714*) in the LDLR gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with familial hypercholesterolemia (PMID: 12436241). This variant has been reported in individuals in the Universal Mutation Database (PMID: 12124988). ClinVar contains an entry for this variant (Variation ID: 225183). This variant is also known as E693X in the literature. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525). For these reasons, this variant has been classified as Pathogenic.

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