ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.551G>C (p.Cys184Ser)

dbSNP: rs121908039
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel RCV000495884 SCV004022388 likely pathogenic Hypercholesterolemia, familial, 1 2023-03-20 reviewed by expert panel curation The NM_000527.5(LDLR):c.551G>C (p.Cys184Ser) variant is classified as Likely pathogenic for Familial Hypercholesterolemia by applying evidence codes (PM1, PM2, PP3, PP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM1 - Variant meets PM2 and alters Cys184, one of the cysteine residues listed. PM2 - This variant is absent from gnomAD (gnomAD v2.1.1). PP3 - REVEL = 0.871. It is above 0.75. PP4 - Variant meets PM2 and is identified in 1 index case who fulfills DLCN>=6 criteria for FH from Service de Biochimie et de Biologie Moléculaire, Hospices Civils de Lyon, Lyon, France, after alternative causes for high cholesterol were excluded.
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000495884 SCV000583703 pathogenic Hypercholesterolemia, familial, 1 2017-03-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588844 SCV000697239 uncertain significance not provided 2016-11-22 criteria provided, single submitter clinical testing Variant summary: The LDLR c.551G>C (p.Cys184Ser) variant involves the alteration of a conserved nucleotide. This variant is located in the Low-density lipoprotein (LDL) receptor class A repeat domain (InterPro). Although the substitution does not exhibit a shift in polarity, 5/5 in silico tools predict a damaging outcome for this variant. This variant is absent in 121044 control chromosomes. One database lists this variant in an individual without clinical information. Other variants affecting the same amino acids, p.Cys184Arg, p.Cys184Tyr, p.Cys184Trp, have been clssified as pathogenic/likely pathogenic in ClinVar. Taken together, this variant is classified as VUS-possibly pathogenic.

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.