Submission Details

MYPN was originally evaluated for DCM by the ClinGen DCM GCEP on 23 July 2020. Evidence of the association of this gene with DCM was re-evaluated using SOP v10 on 5th March 2025. As a result, the classification did not change. A summary of the information contributing to the classification of this gene at the time of re-evaluation is summarized herein. MYPN was first reported in relation to autosomal dominant dilated cardiomyopathy (DCM) in 2008 (Dubosq-Bidot et al., 2008, PMID 18006477). Human genetic evidence supporting this gene-disease relationship includes case-level data. Variants (50 missense, 2 frameshift) in this gene have been reported in at least 56 probands in 21 publications. However, variants in this gene segregated with disease in only one family (3 additional family members) and a case-control study (Mazzarotto et al., 2020, PMID 31983221) found no enrichment of MYPN rare variants in two DCM cohorts compared to controls. This gene-disease assertion is supported by one animal model (mouse; Filomena et al., 2021, PMID 34558411), expression studies and protein interaction studies. MYPN has also been curated by the hereditary cardiovascular disease Gene Curation Expert Panel for hypertrophic cardiomyopathy (Disputed, June 14, 2023) and by the congenital myopathies Gene Curation Expert Panel for nemaline myopathy 11 (Definitive, June 17, 2020). In summary, there is limited evidence to support this gene-disease relationship. More evidence is needed to support the relationship of MYPN with autosomal dominant DCM. This classification was approved by the ClinGen Dilated Cardiomyopathy Working Group on 5th March 2025 (SOP Version 10).