ClinVar Miner

Submissions for variant NC_000019.10:g.(?_11100203)_(11102806_?)del

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000533042 SCV000627005 pathogenic Hypercholesterolemia, familial, 1 2017-08-03 criteria provided, single submitter clinical testing This variant is an in-frame deletion of the genomic region encompassing exons 2-3 of the LDLR gene. It preserves the integrity of the reading frame. Deletions encompassing exons 2-3 of the LDLR gene have been reported in several individuals affected with hypercholesterolemia and has been found to segregate with the disease in one family (PMID: 12052488, 1301956, 2318961, 2805380 ). For these reasons, this variant has been classified as Pathogenic.
Invitae RCV001858053 SCV002137396 pathogenic Familial hypercholesterolemia 2022-03-08 criteria provided, single submitter clinical testing This variant is a gross deletion of the genomic region encompassing exon(s) 2-3 of the LDLR gene. This variant would be expected to be in-frame, preserving the integrity of the reading frame. A similar copy number variant has been observed in individuals with familial hypercholesterolemia (PMID: 1301956, 2544509, 2805380, 12052488). It has also been observed to segregate with disease in related individuals. This variant affects a cysteine residue located within an LDLRA or epidermal-growth-factor (EGF)-like domains 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: 7548065, 7603991, 7979249). In addition, missense substitutions within the LDLRA and EGF-like domains affecting cysteine residues are overrepresented among patients with hypercholesterolemia (PMID: 18325082). For these reasons, this variant has been classified as 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.