ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.1753C>A (p.Gln585Lys) (rs140101603)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481136 SCV000569578 uncertain significance not provided 2017-03-23 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the APOB gene. The Q585K variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Q585K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Nevertheless, this substitution occurs at a position that is not conserved, and lysine is tolerated at this position in several species. Furthermore, in silico analysis predicts this variant likely does not alter the protein structure/function.
Color RCV000771614 SCV000904218 uncertain significance Familial hypercholesterolemias 2018-06-04 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant (also known as p.Gln558Lys in the mature protein) is a missense variant located in the beta alpha 1 domain of the APOB protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. This variant occurs in multiple mammalian species, suggesting that it may be functionally tolerated. 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 8/24620 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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