MYH2 was first reported in relation to autosomal dominant proximal myopathy and ophthalmoplegia in 2000 (Martinsson et al., PMID: 11114175). Evidence supporting this gene-disease relationship includes case-level data from 5 probands in 5 publications (PMIDs: 11114175, 23489661, 25529940, 36380287, 36774715), with four unique variants (3 missense and 1 splice site) predominantly found in the filament assembly region except for Glu706Lys in the SH1 helix domain. A dominant negative mechanism has been suggested however has not been established. This gene-disease association is also supported by experimental evidence, including expression evidence (PMID: 7545970) in type IIa muscle fibers, functional alteration in patient cells (PMID: 17005402), and a C. elegans model (PMID: 16130113). In summary, there is moderate 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.
Of note, MYH2 has also been reported in relation to autosomal recessive proximal myopathy and ophthalmoplegia. Due to the proposed difference in mechanism, loss of function, 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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