ClinVar Miner

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

gnomAD frequency: 0.00003  dbSNP: rs778424518
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Total submissions: 6
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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 (https://doi.org/10.1101/2021.03.17.21252755). 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

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