ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.2282C>T (p.Thr761Met) (rs138477254)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER_CC_NCGL; University of Washington Medical Center RCV000148565 SCV000190278 likely benign Hypercholesterolaemia 2014-06-01 no assertion criteria provided research
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000237277 SCV000503476 uncertain significance Familial hypercholesterolemia 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 2/Software predictions: Conflicting
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000162013 SCV000189589 not provided not provided no assertion provided in vitro
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000237277 SCV000733832 likely benign Familial hypercholesterolemia no assertion criteria provided clinical testing
Fundacion Hipercolesterolemia Familiar RCV000237277 SCV000607689 uncertain significance Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
Iberoamerican FH Network RCV000237277 SCV000748062 uncertain significance Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
Integrated Genetics/Laboratory Corporation of America RCV000780383 SCV000917589 uncertain significance not specified 2018-10-01 criteria provided, single submitter clinical testing Variant summary: LDLR c.2282C>T (p.Thr761Met) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.5e-05 in 246126 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in LDLR Familial Hypercholesterolemia (4.5e-05 vs 0.0013), allowing no conclusion about variant significance. The variant, c.2282C>T, has been reported in the literature in individuals affected with Familial Hypercholesterolemia and myocardial infarction (Thormaehlen_2015, Fouchier_2005, Brusgaard_2006, Amendola_2015). These reports do not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Thormaehlen_2015). Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (VUS x4, pathogenic x1). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
LDLR-LOVD, British Heart Foundation RCV000237277 SCV000295930 uncertain significance Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000237277 SCV000606626 benign Familial hypercholesterolemia no assertion criteria provided research
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000237277 SCV000583940 pathogenic Familial hypercholesterolemia 2017-03-30 criteria provided, single submitter 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.