FLAD1 was first reported in relation to autosomal recessive myopathy with abnormal lipid metabolism in 2014 (Taylor RW, et al., 2014; PMID: 25058219). Twelve variants (including missense, in-frame deletions, nonsense, splicing, and frameshift) have been reported in 13 probands, and three additional family members, in seven publications (PMIDs: 30061063, 30982706, 25058219, 30311138, 27259049, 31392824, 30427553). This gene-disease association is also supported by experimental evidence including its biochemical function in catalysis of FMN into FAD (PMID: 16643857), which is altered in patient cells (PMID: 27259049), as well as an expression pattern consistent with disease (PMID: 20060505), and a C. elegans model (PMID: 22306247). In summary, FLAD1 is definitively associated with autosomal recessive myopathy with abnormal lipid metabolism. This classification was approved by the ClinGen FAO GCEP 12/16/2020 (SOP Version [7]). This gene-disease pair was originally evaluated by the FAO GCEP on 06/12/2018. It was reevaluated on 12/15/2020. Additional genetic evidence was included from new publications (PMIDs: 30061063, 30982706, 30311138, 31392824, 30427553). As a result of this reevaluation, the classification was upgraded from moderate to definitive.
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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