ClinVar Miner

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

dbSNP: rs143872778
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Total submissions: 8
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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 (https://doi.org/10.1016/j.gim.2021.09.012). 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

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