ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.4532C>T (p.Thr1511Ile) (rs146247063)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523023 SCV000619304 uncertain significance not provided 2017-07-19 criteria provided, single submitter clinical testing The T1511I variant in the APOB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T1511I variant is observed in 3/6612 (0.045%) alleles from individuals of Finnish European background in the ExAC dataset (Lek et al., 2016). The T1511I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret T1511I as a variant of uncertain significance.
Robarts Research Institute,Western University RCV000660688 SCV000782856 uncertain significance Familial hypercholesterolemia 2018-01-02 criteria provided, single submitter clinical testing
Color RCV000771242 SCV000903342 uncertain significance Familial hypercholesterolemias 2018-06-04 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant (also known as p.Thr1484Ile in the mature protein) is located in the beta 1 domain of the APOB protein. Computational prediction tools and conservation analyses suggest that this variant may not impact 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 has been identified in 43/277142 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

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