SCARB2 was first reported in relation to autosomal recessive Progressive Myoclonic Epilepsy (PME) in 2008 (Berkovic et al., PMID: 18308289). At least 25 variants have been reported in humans. Renal dysfunction has been reported in about 50% of patients with SCARB2-related conditions, and therefore may represent phenotypic variability associated with PME (Tian et al. 2018, PMID: 29605618). Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 6 unrelated probands in 3 publications (Berkovic et al. 2008, PMID: 18308289; Balreira et al. 2008, PMID: 18424452; Fu et al. 2014, PMID: 23659519). More evidence is available in the literature, but the maximum score for genetic evidence has been reached. The mechanism for disease is homozygous loss of function (Blanz et al. 2010, PMID: 19933215). This gene-disease association is supported by in vitro functional assays using patient cells (Blanz et al. 2010, PMID: 19933215). In summary, SCARB2 is definitively associated with autosomal recessive Progressive Myoclonic Epilepsy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
This classification was approved by the ClinGen EIEE Working Group on 8/18/20 (SOP Version 7).
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