ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1691A>G (p.Asn564Ser) (rs758194385)

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
Cardiovascular Biomarker Research Laboratory,Mayo Clinic RCV000210237 SCV000266306 likely pathogenic Familial hypercholesterolemia 1 2015-08-31 criteria provided, single submitter research MAF =<0.3%, likely pathogenic based on the integrative in-silico score, LDL-C >=160 mg/dL, previously reported as P/LP in the literature
LDLR-LOVD, British Heart Foundation RCV000210237 SCV000295582 likely pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Fundacion Hipercolesterolemia Familiar RCV000210237 SCV000607624 likely pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Invitae RCV001201346 SCV000831365 likely pathogenic Familial hypercholesterolemia 2020-05-14 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 564 of the LDLR protein (p.Asn564Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs758194385, ExAC 0.01%). This variant has been reported in several individuals affected with hypercholesterolemia (PMID: 9654205, 18718593, 20538126, 23375686, 28145427). This variant is also known as N543S in the literature. ClinVar contains an entry for this variant (Variation ID: 224616). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Brunham Lab, Centre for Heart and Lung Innovation,University of British Columbia RCV000210237 SCV001432663 pathogenic Familial hypercholesterolemia 1 2019-05-23 criteria provided, single submitter research
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000210237 SCV000606486 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research
Biochemical Molecular Genetic Laboratory,King Abdulaziz Medical City RCV000210237 SCV001190840 likely pathogenic Familial hypercholesterolemia 1 2020-02-05 no assertion criteria provided clinical testing
Natera, Inc. RCV001201346 SCV001461314 likely pathogenic Familial hypercholesterolemia 2020-09-16 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.