ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.9633C>A (p.Asn3211Lys) (rs748318755)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Robarts Research Institute,Western University RCV000660709 SCV000782898 uncertain significance Familial hypercholesterolemia 2018-01-02 criteria provided, single submitter clinical testing
Color RCV000776513 SCV000912109 uncertain significance Familial hypercholesterolemias 2018-10-01 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant (also known as p.Asn3184Lys in the mature protein) is located in the beta 2 domain of the APOB protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 4/245310 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Invitae RCV000805794 SCV000945763 uncertain significance Hypercholesterolemia, autosomal dominant, type B; Hypobetalipoproteinemia, familial, 1 2018-08-28 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 3211 of the APOB protein (p.Asn3211Lys). The asparagine residue is weakly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is present in population databases (rs748318755, ExAC 0.005%). This variant has not been reported in the literature in individuals with APOB-related disease. ClinVar contains an entry for this variant (Variation ID:548072). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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