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In a cross-sectional sequencing study of 51 professional ballet dancers (32 participants sequenced), 60 connective tissue disorder–associated genes were screened. A single NOTCH1 variant was observed in one dancer (3.1%) with no identified pathogenic alleles or enrichment in hypermobility spectrum scores (PMID:31765226). The study did not report any segregation of NOTCH1 variants with affected relatives or syndrome-level hypermobility beyond population prevalence.
Overall, there is limited clinical validity for NOTCH1 in connective tissue disorder: only one uncorrelated variant detected in an asymptomatic individual, no familial segregation, and no functional data supporting pathogenicity in CTD. Additional case-level evidence, segregation studies, and connective tissue–specific functional assays are required to evaluate any potential role of NOTCH1 in hypermobility phenotypes.
Gene–Disease AssociationLimitedOne NOTCH1 variant identified in a single asymptomatic dancer with no phenotype correlation (PMID:31765226). Genetic EvidenceLimitedSingle variant occurrence without probands, segregation, or case-level evidence. Functional EvidenceNo reported evidenceNo functional studies address NOTCH1 variants in connective tissue disorder context. |