ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2297C>T (p.Thr766Ile)

dbSNP: rs879255173
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
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel RCV000237943 SCV005688689 uncertain significance Hypercholesterolemia, familial, 1 2024-10-28 reviewed by expert panel curation The NM_000527.5(LDLR):c.2297C>T (p.Thr766Ile) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2 and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 28 October 2024. The supporting evidence is as follows: PM2: PopMax MAF = 0.00001098 (0.001098%) in South Asian exomes (gnomAD v4.1.0). PP4: Variant meets PM2 and is identified in one index case who fulfils DLCN criteria for probable FH after alternative causes of high cholesterol excluded, reported in PMID 16250003 (Fouchier et al., 2005), The Netherlands.
LDLR-LOVD, British Heart Foundation RCV000237943 SCV000295937 uncertain significance Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Fulgent Genetics, Fulgent Genetics RCV000237943 SCV002780233 uncertain significance Hypercholesterolemia, familial, 1 2021-07-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV004992129 SCV005609300 uncertain significance Cardiovascular phenotype 2024-07-09 criteria provided, single submitter clinical testing The p.T766I variant (also known as c.2297C>T), located in coding exon 15 of the LDLR gene, results from a C to T substitution at nucleotide position 2297. The threonine at codon 766 is replaced by isoleucine, an amino acid with similar properties. This alteration has been reported in a familial hypercholesterolemia cohort (Fouchier SW et al. Hum Mutat, 2005 Dec;26:550-6). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237943 SCV000606628 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.