ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.28T>C (p.Trp10Arg)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237793 SCV000294417 likely pathogenic Hypercholesterolemia, familial, 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 RCV000237793 SCV000503092 likely pathogenic Hypercholesterolemia, familial, 1 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1, family members =2 with co-segregation / software predictions: conflicting
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000237793 SCV000583623 pathogenic Hypercholesterolemia, familial, 1 2017-03-30 criteria provided, single submitter clinical testing ACMG Guidelines: Likely Pathogenic (ii)
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000237793 SCV000588480 pathogenic Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research
Ambry Genetics RCV002436068 SCV002751844 likely pathogenic Cardiovascular phenotype 2019-04-30 criteria provided, single submitter clinical testing The p.W10R variant (also known as c.28T>C), located in coding exon 1 of the LDLR gene, results from a T to C substitution at nucleotide position 28. The tryptophan at codon 10 is replaced by arginine, an amino acid with dissimilar properties. This variant has been described in familial hypercholesterolemia (FH) cohorts, although clinical details were limited (Fouchier SW et al. Hum. Mutat., 2005 Dec;26:550-6; Jannes CE et al. Atherosclerosis, 2015 Jan;238:101-7). An alternate nucleotide change at this position, p.W10R c.28T>A, was reported to be de novo in a pediatric FH case, and functional activity in skin fibroblasts showed reduced LDLR activity (Cassanelli S et al. Clin. Genet., 1998 May;53:391-5). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237793 SCV000605997 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000237793 SCV000733809 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV001699170 SCV001920172 likely pathogenic not provided no assertion criteria provided clinical testing

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.