ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1586+1G>A

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000238067 SCV000295508 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 RCV000238067 SCV000503369 likely pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 3
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000238067 SCV000588593 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Integrated Genetics/Laboratory Corporation of America RCV001290569 SCV001478645 pathogenic Familial hypercholesterolemia 2021-01-28 criteria provided, single submitter clinical testing Variant summary: LDLR c.1586+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5 prime splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251100 control chromosomes. c.1586+1G>A has been reported in the literature in multiple individuals affected with Familial Hypercholesterolemia (e.g. Bertolini_2013, Tada_2020). These data indicate that the variant is very likely to be associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000238067 SCV000606458 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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