ClinVar Miner

Submissions for variant NM_005506.4(SCARB2):c.277G>A (p.Glu93Lys) (rs145870223)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000188812 SCV000615018 uncertain significance not specified 2017-03-01 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000734839 SCV000863013 uncertain significance not provided 2018-08-23 criteria provided, single submitter clinical testing
GeneDx RCV000188812 SCV000242436 uncertain significance not specified 2016-09-29 criteria provided, single submitter clinical testing A variant of unknown significance has been identified in the SCARB2 gene. The E93K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The E93K 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. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense pathogenic variants in nearby residues have not been reported in the Human Gene Mutation Database in association (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000462122 SCV000545818 uncertain significance Progressive myoclonic epilepsy 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 93 of the SCARB2 protein (p.Glu93Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs145870223, ExAC 0.03%). This variant has not been reported in the literature in individuals with SCARB2-related disease. ClinVar contains an entry for this variant (Variation ID: 206724). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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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