ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1836C>A (p.Ala612=)

dbSNP: rs143872778
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel RCV000508762 SCV004022370 uncertain significance Hypercholesterolemia, familial, 1 2023-03-20 reviewed by expert panel curation NM_000527.5(LDLR):c.1836C>A (p.Ala612=) variant is classified as Uncertain significance - conflicting evidence for Familial Hypercholesterolemia by applying evidence code PM2, BP4 and BP7 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines ( The supporting evidence is as follows: PM2 - PopMax MAF = 0.00015 (0.015%) in East Asian exomes and genomes (gnomAD v2.1.1). Frequency is higher in "other" population exomes and genomes but number of allele is below 10000 BP4 - No REVEL, splicing evaluation required. Functional data on splicing not available. - Variant is exonic and at least 50bp downstream from canonical acceptor site but it does not create GT. - There is a GT nearby. MES scores: variant cryptic = -16.35, wt cryptic = -12.61, canonical donor = 4.48. Ratio variant cryptic/wt cryptic: -16.35/-12.61 = 1.30 --- it is above 1.1 Ratio variant cryptic/canonical donor: -16.35/4.48 = -3.65 --- it is not above 0.9 Variant is not predicted to alter splicing. BP7 - Variant is synonymous and meets BP4.
Invitae RCV001188069 SCV000627023 likely benign Familial hypercholesterolemia 2024-01-29 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001188069 SCV001355015 likely benign Familial hypercholesterolemia 2017-07-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV002413394 SCV002716331 likely benign Cardiovascular phenotype 2022-05-16 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003330735 SCV004037851 likely benign not specified 2023-08-01 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000508762 SCV004822507 likely benign Hypercholesterolemia, familial, 1 2024-02-05 criteria provided, single submitter clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000508762 SCV000606530 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research
Natera, Inc. RCV001188069 SCV002086852 uncertain significance Familial hypercholesterolemia 2019-10-28 no assertion criteria provided clinical testing

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.