ClinVar Miner

Submissions for variant NM_174936.3(PCSK9):c.286C>T (p.Arg96Cys) (rs185392267)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781705 SCV000919968 pathogenic Familial hypercholesterolemia 2018-07-30 criteria provided, single submitter clinical testing Variant summary: PCSK9 c.286C>T (p.Arg96Cys) results in a non-conservative amino acid change located in the Peptidase S8 propeptide/proteinase inhibitor I9 of 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 2.2e-05 in 277054 control chromosomes (gnomAD). c.286C>T has been reported in the literature in three members of a family with Familial Hypercholesterolemia (Hopkins_2015), and was reported along with a pathogenic APOB variant in a severly affected patient (Elbitar_2018). These data indicate that the variant is likely to be associated with disease. Functional studies proved that the p.Arg96Cys mutation leads to increased LDL receptor degradation (Elbitar_2018). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Color Health, Inc RCV000781705 SCV001339319 uncertain significance Familial hypercholesterolemia 2020-03-21 criteria provided, single submitter clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000508933 SCV000606686 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001528542 SCV001740424 uncertain significance 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.