ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1599G>A (p.Trp533Ter) (rs879254952)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237743 SCV000295530 pathogenic Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000237743 SCV000322963 pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research 0/208 non-FH alleles
Fundacion Hipercolesterolemia Familiar RCV000237743 SCV000607615 pathogenic Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
Invitae RCV000237743 SCV000825962 pathogenic Familial hypercholesterolemia 2018-04-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp533*) in the LDLR gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with familial hypercholesterolemia (PMID: 10447263, 20828696, 29213121). ClinVar contains an entry for this variant (Variation ID: 251927). Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525). For these reasons, this variant has been classified as Pathogenic.
Color RCV000775073 SCV000909175 pathogenic Familial hypercholesterolemias 2018-08-31 criteria provided, single submitter clinical testing Pathogenic variant based on current evidence: This variant changes 1 nucleotide in exon 11 of the LDLR gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in individuals affected with familial hypercholesterolemia (PMID: 10447263, 24627126, 29213121) and has been said to segregate with disease in three individuals from a family (PMID: 24627126). This variant is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Loss of LDLR function is a known mechanism of disease. Based on available evidence, this variant is 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.