ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1135T>C (p.Cys379Arg)

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
LDLR-LOVD, British Heart Foundation RCV000237249 SCV000295242 likely pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Invitae RCV000791396 SCV000544680 pathogenic Familial hypercholesterolemia 2020-03-14 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 379 of the LDLR protein (p.Cys379Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant has been reported in the homozygous and heterozygous state in individuals affected with hypercholesterolemia and segregates with the disease in families (PMID: 25682026, 23375686, 11317362, 15241806, 9852677). This variant is also known as FH Naples-1 and C358R in the literature. Experimental studies have shown that this missense change reduces LDLR receptor activity (PMID: 1301956). Accordingly, lymphocytes collected from individuals carrying this variant show a reduction in the ability to bind LDL (PMID: 21865347). This variant affects a cysteine residue located within an epidermal-growth-factor (EGF)–like domain of the LDLR protein. Cysteine residues in these domains have been shown to be involved in the formation of disulfide bridges, which are critical for protein structure and stability (PMID: 3495735, 4750422). In addition, missense substitutions within the LDLR EGF-like domains affecting cysteine residues are overrepresented among patients with hypercholesterolemia (PMID: 18325082). For these reasons, this variant has been classified as Pathogenic.
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000237249 SCV000588556 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Fundacion Hipercolesterolemia Familiar RCV000237249 SCV000607564 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000237249 SCV001433520 pathogenic Familial hypercholesterolemia 1 2020-01-14 criteria provided, single submitter clinical testing
Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II RCV000237249 SCV001653624 pathogenic Familial hypercholesterolemia 1 2021-05-24 criteria provided, single submitter clinical testing Reduced activity, in stimulated T-lymphocytes and EBV-transformed B-lymphocytes.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000237249 SCV000606334 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.