biostudies-literatureUnknown11(1-2)Brauers EBundesministerium für Bildung und ForschungMinisterium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-WestfalenDeutsche Gesellschaft für Muskelkranke e.V.Deutsche ForschungsgemeinschaftRWTH Aachen University<h4>Purpose</h4>In the era of next-generation sequencing, we are increasingly confronted with sequence variants of unknown significance. This phenomenon is also known for variations in Caveolin-3 and can complicate the molecular diagnosis of the disease. Here, we aimed to study the ambiguous character of the G56S Caveolin-3 variant.<h4>Experimental design</h4>A comprehensive approach combining genetic and morphological studies of muscle derived from carriers of the G56S Caveolin-3 variant were carried out and linked to biochemical assays (including phosphoblot studies and proteome profiling) and morphological investigations of cultured myoblasts.<h4>Results</h4>Muscles showed moderate chronic myopathic changes in all carriers of the variant. Myogenic RCMH cells expressing the G56S CaveolinProteomics. Clinical applicationshttps://www.ebi.ac.uk/biostudies/studies/S-EPMC5248598biostudies-literatureThe Caveolin-3 G56S sequence variant of unknown significance: Muscle biopsy findings and functional cell biological analysis.PMC524859841/12MD-Net P4DFG ZA 639/1-101GM0887Thoma SKress WWeis JBrauers EMohanadas NZahedi RPHausler MBeckmann ABauer HSenderek JKollipara LRoos AfalseThe Caveolin-3 G56S sequence variant of unknown significance: Muscle biopsy findings and functional cell biological analysis.<h4>Purpose</h4>In the era of next-generation sequencing, we are increasingly confronted with sequence variants of unknown significance. This phenomenon is also known for variations in Caveolin-3 and can complicate the molecular diagnosis of the disease. Here, we aimed to study the ambiguous character of the G56S Caveolin-3 variant.<h4>Experimental design</h4>A comprehensive approach combining genetic and morphological studies of muscle derived from carriers of the G56S Caveolin-3 variant were carried out and linked to biochemical assays (including phosphoblot studies and proteome profiling) and morphological investigations of cultured myoblasts.<h4>Results</h4>Muscles showed moderate chronic myopathic changes in all carriers of the variant. Myogenic RCMH cells expressing the G56S Caveolin2017-01-01T00:00:00Z2017 Jan2026-04-07T13:46:55.374Z2019-03-27T02:34:34ZS-EPMC52485982773925410.1002/prca.201600007