MYBPC3 was originally evaluated for autosomal recessive DCM by the ClinGen DCM GCEP on 16 May 2025. MYBPC3 was first reported in relation to autosomal recessive DCM in 2019 (Kolokotronis K, et al., PMID: 30924982). Human genetic evidence supporting this gene-disease relationship includes case-level data. Two probands with DCM have been reported in two publications (Kolokotronis et al, PMID: 30924982; Blagova et al, PMID: 33101033). One probands was homozygous for a small in-frame deletion and the other compound heterozygous for a whole gene MYBPC3 deletion and an MYBPC3 missense variant. This gene-disease association is supported by multiple animal models (mouse), expression studies, and rescue studies in two mouse models. MYBPC3 has not been assessed in any other autosomal recessive conditions but has been assessed separately for autosomal dominant dilated cardiomyopathy (limited, May 16, 2025), hypertrophic cardiomyopathy (definitive, October 7, 2021), arrhythmogenic right ventricular cardiomyopathy (limited, August 6, 2019), and congenital heart disease (limited, July 8, 2024). In summary, there is limited evidence to support this gene-disease relationship. More evidence is needed to support the relationship of MYBPC3 with autosomal recessive DCM. This classification was approved by the ClinGen Dilated Cardiomyopathy Working Group on 16th May 2025 (SOP Version 10).
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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