The relationship between AARS and autosomal recessive Undetermined Early-onset Epileptic Encephalopathy was evaluated using the ClinGen Clinical Validity Framework as of 11/20/2018. Variants in AARS were first reported in humans with this disease as early as 2015 (Simons et al., PMID 25817015). At least 1 frameshift and 3 missense variants have been reported in humans. Evidence supporting this gene-disease relationship includes case-level and experimental data. Variants in this gene have been reported in at least 3 probands in 2 publications (PMID: 25817015, 28493438). Variants in this gene segregated with disease in 2 additional family members. This gene-disease association is supported by functional studies that show variants' affects on yeast growth and catalytic efficiency in patient-derived cell lines. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Epilepsy Working Group on 11/20/2018.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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