ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.710G>A (p.Arg237His) (rs148171426)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000417334 SCV000503228 likely benign 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 RCV000775604 SCV000909968 uncertain significance Familial hypercholesterolemia 2018-10-10 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant (also known as p.Arg216His in the mature protein) is a missense variant located in the sixth LDLR type A repeat of the ligand binding domain of the LDLR protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. In a cell-based high-throughput LDLR activity assay, this variant has been shown to be non-disruptive for LDLR function (PMID 25647241). To our knowledge, this variant has not been reported in individuals affected with in familial hypercholesterolemia in the literature. This variant has been identified in 14/277236 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.