The relationship between NDUFV2 and Leigh syndrome spectrum was evaluated using the ClinGen Clinical Validity Framework as of November 20, 2019. The NDUFV2 gene encodes the NADH:ubiquinone oxidoreductase (complex I) flavoprotein 2, a core subunit of mitochondrial complex I. Defects of this protein lead to complex I deficiency.
The NDUFV2 gene has been reported in relation to autosomal recessive Leigh syndrome spectrum in a single publication in 2011 (PMID: 26008862). Evidence supporting this gene-disease relationship includes case-level data and experimental data.
This curation included one homozygous variant identified in one case in one publication (PMID: 26008862). No segregation data were available. Loss of function is implicated as the mechanism of disease. This gene-disease association is also supported by known protein interactions (PMID: 27509854).
In addition, variants in NDUFV2 have been associated with other phenotypes outside the scope of the Leigh syndrome spectrum gene-disease curation.
In summary, there is limited evidence to support a gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the NICHD U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel November 20, 2019 (SOP Version 7).
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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