ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1221C>T (p.His407=)

gnomAD frequency: 0.00003  dbSNP: rs778424518
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel RCV000495935 SCV002817139 uncertain significance Hypercholesterolemia, familial, 1 2022-08-29 reviewed by expert panel curation The NM_000527.5(LDLR):c.1221C>T (p.His407=) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2, BP4, BP7) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines ( The supporting evidence is as follows: PM2 - This variant is absent from gnomAD (gnomAD v2.1.1). BP4 - No REVEL, splicing evaluation required. Functional data not available A) not on limits B) does not create AG Variant not predicted to alter splicing BP7 - Variant is synonymous and meets BP4.
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000495935 SCV000583808 likely pathogenic Hypercholesterolemia, familial, 1 2017-03-30 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000776579 SCV000912192 likely benign Familial hypercholesterolemia 2018-07-02 criteria provided, single submitter clinical testing
Invitae RCV000776579 SCV002413978 likely benign Familial hypercholesterolemia 2023-11-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002356810 SCV002655440 likely benign Cardiovascular phenotype 2017-08-11 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000495935 SCV000606365 benign 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.