MYH2 was first reported in relation to autosomal recessive proximal myopathy and ophthalmoplegia in 2000 (Tajsharghi et al., PMID: 20418530). Evidence supporting this gene-disease relationship includes case-level data from 8 probands in 3 publications (PMIDs: 20418530, 23388406, 24193343), with ten unique variants (including missense, in-frame deletions, frameshifts, and splice sites), having a loss of function mechanism. This gene-disease association is also supported by experimental evidence, including expression evidence (PMID: 7545970) in type IIa muscle fibers and a C. elegans model (PMID: 16130113). In summary, MYH2 is definitively associated with autosomal recessive proximal myopathy and ophthalmoplegia. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. Of note, MYH2 has also been reported in relation to autosomal dominant proximal myopathy and ophthalmoplegia. Due to the proposed difference in mechanism, dominant negative, those cases were considered in a separate curation.
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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