ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.762G>T (p.Gln254His)

dbSNP: rs764526789
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
LDLR-LOVD, British Heart Foundation RCV000237305 SCV000294957 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
All of Us Research Program, National Institutes of Health RCV000237305 SCV004837568 uncertain significance Hypercholesterolemia, familial, 1 2023-10-06 criteria provided, single submitter clinical testing This missense variant replaces glutamine with histidine at codon 255 of the LDLR protein. This variant is also known as p.Gln233His in the mature protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with familial hypercholesterolemia (PMID: 15823276, 16250003, 23833242, 32770674). In several of these instances, this variant has been reported to occur in cis or in unknown phase with p.Cys255Gly (PMID: 15823276, 23833242, 32770674). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same codon, p.Gln254Pro, is considered to be disease-causing (ClinVar variation ID: 251437), suggesting that glutamine at this position is important for LDLR protein function. The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237305 SCV000606218 pathogenic Hypercholesterolemia, familial, 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.