ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.9221A>G (p.Tyr3074Cys) (rs372902533)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000232693 SCV000284777 uncertain significance Familial hypercholesterolemia 2; Hypobetalipoproteinemia, familial, 1 2016-03-27 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 3074 of the APOB protein (p.Tyr3074Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs372902533, ExAC 0.01%) but has not been reported in the literature in individuals with a APOB-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000775208 SCV000909451 uncertain significance Familial hypercholesterolemia 2018-05-15 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant (also known as p.Tyr3047Cys in the mature protein) is a missense variant located in the beta2 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 the variant been reported in individuals affected with familial hypercholesterolemia in the literature. This variant is rare in the general population and has been identified in 6/245840 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845548 SCV000987668 uncertain significance not provided criteria provided, single submitter clinical testing

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