OBSCN was originally evaluated for DCM by the ClinGen DCM GCEP on June 11 2020. Evidence of the association of this gene with DCM was re-evaluated using SOP v10 on February 7 2025. As a result, the classification is unchanged. A summary of the information contributing to the classification of this gene at the time of re-evaluation is summarized herein:
OBSCN was first reported in relation to autosomal dominant dilated cardiomyopathy (DCM) in 2015 (Marston et al., 2015, PMID: 26406308). Human genetic evidence supporting this gene-disease relationship includes case-level data. Several variants (including missense and frameshift variants) have been reported in humans with DCM (Marston et al., 2015, PMID: 26406308; Rowland et al., 2015, PMID: 27855815); however, all but one (missense) variant are present in control populations at a frequency higher than expected for dominant DCM. The gene-disease assertion is supported by expression studies and in vitro functional assays. Expression studies have documented low levels of Obscurin within the heart (Young et al., 2001, PMID: 11448995; Marston et al., 2015, PMID: 26406308). Yeast 2 hybrid and in vitro binding assay noted an interaction between Obscurin and the titin Z-disc (Young et al., 2001, PMID: 11448995). In summary, there is limited evidence to support this gene-disease relationship. More evidence is needed to support the relationship of OBSCN with autosomal dominant DCM. This classification was approved by the ClinGen Dilated Cardiomyopathy Working Group on February 7, 2025. (SOP Version 7).
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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