ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.10780T>C (p.Trp3594Arg)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Robarts Research Institute,Western University RCV000408771 SCV000484829 uncertain significance Familial hypercholesterolemia 1 criteria provided, single submitter clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000408771 SCV000588454 uncertain significance Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Invitae RCV000655122 SCV000777047 benign Familial hypercholesterolemia 2; Hypobetalipoproteinemia, familial, 1 2020-10-27 criteria provided, single submitter clinical testing
Color Health, Inc RCV000776113 SCV000910986 likely benign Familial hypercholesterolemia 2017-07-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001255528 SCV001431977 likely benign not specified 2020-08-31 criteria provided, single submitter clinical testing Variant summary: APOB c.10780T>C (p.Trp3594Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00064 in 251080 control chromosomes, predominantly at a frequency of 0.0087 within the African or African-American subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 139 fold of the estimated maximal expected allele frequency for a pathogenic variant in APOB causing Familial Hypercholesterolemia phenotype (6.3e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.10780T>C has been reported in the literature in individuals affected with Hypercholesterolemia (example: Ahmad_2012, Kusters_2013). These reports however, do not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign or uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV001255528 SCV001433395 benign not specified 2020-01-23 criteria provided, single submitter clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000408771 SCV000605955 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research

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.