MYOZ2 was first reported in relation to hypertrophic cardiomyopathy (HCM) in humans in 2007 (Osio et al., PMID: 17347475). MYOZ2 encodes a protein which belongs to a family of sarcomeric proteins that bind to calcineurin and are important in calcineurin signaling. The MYOZ2 gene has been related with HCM in 7 probands across 4 publications. One missense variant with experimental evidence to support its pathogenicity was identified in a patient and was shown to segregate with 5 additional family members (Osio et al., 2007, PMID: 17347475). Five additional unique variants with little to no experimental evidence to support their pathogenicity were reported (Osio et al., 2007, PMID: 17347475; Posch et al., 2008, PMID: 18591919; Cecconi M, et al., 2016, PMID: 27600940). Another unique missense variant was identified in a proband who also harbored a variant in MYH7 and was excluded as causative (Guo et al., 2017, PMID: 28296734). The mechanism for disease is unknown.
The gene-disease relationship is supported by expression data in the heart (Frey N, et al., 2000, PMID: 11114196), a mouse model that exhibits features of hypertrophic cardiomyopathy including left ventricular hypertrophy and interstitial cardiac fibrosis (Ruggiero A, et al., 2013, PMID: 22987565), and protein interaction with ACTN2 (Frey N, et al., 2000, PMID: 11114196). In summary, the evidence to support the gene-disease association between MYOZ2 and HCM is disputed as there has been a lack of supportive evidence since the previous curation and the points were reduced due to the new SOP. More evidence is needed to either support or entirely refute the role MYOZ2 plays in this disease. This gene-disease pair was originally evaluated by the ClinGen Hypertrophic Cardiomyopathy Gene Curation Expert Panel on June 26th, 2017. It was reevaluated on October 27th, 2022. As a result of this reevaluation, the classification changed from limited to disputed.
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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