ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1061A>G (p.Asp354Gly) (rs755449669)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237417 SCV000295191 likely pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Robarts Research Institute,Western University RCV000237417 SCV000484713 likely pathogenic Familial hypercholesterolemia 1 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation RCV000237417 SCV000540788 likely pathogenic Familial hypercholesterolemia 1 2016-11-05 criteria provided, single submitter clinical testing
Color RCV000775053 SCV000909153 likely pathogenic Familial hypercholesterolemia 2019-04-02 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000237417 SCV001429017 pathogenic Familial hypercholesterolemia 1 2019-07-17 criteria provided, single submitter clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000237417 SCV000606311 pathogenic Familial hypercholesterolemia 1 no assertion criteria provided research
Broad Institute Rare Disease Group,Broad Institute RCV000775053 SCV001422596 uncertain significance Familial hypercholesterolemia 2020-01-22 no assertion criteria provided curation The p.Asp354Gly variant in LDLR has been reported in 4 individuals with familial hypercholesterolemia (PMID: 29353225, 1301956, 20145306, 11810272), and has been identified in 0.003% (1/30616) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs755449669). This variant has also been reported in ClinVar as likely pathogenic (Variation ID: 251639). In vitro functional studies provide some evidence that the p.Asp354Gly variant may slightly impact protein function (PMID: 19040724). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_supporting, PP3, PS4_supporting, PS3_supporting (Richards 2015).

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