Variant Synonymizer: Platform to identify mutations defined in different ways is available now!

VarSy

Over 2,000 gene–disease validation summaries are now available—no login required!

Browse Summaries

CAPN3 – Autosomal dominant limb-girdle muscular dystrophy

A recurrent in-frame deletion in CAPN3, c.643_663del (p.Ser215_Gly221del), has been identified in three unrelated autosomal dominant limb-girdle muscular dystrophy families, with late-onset proximal weakness accompanied by myalgia, back pain, and hyperlordosis in the fourth to fifth decades ([PMID:28881388]). The variant segregates with disease in each pedigree, and no pathogenic mutations were found in other known myopathy genes. Muscle Western blot analysis demonstrated reduced calpain-3 expression in all affected individuals, supporting a haploinsufficiency mechanism ([PMID:28881388]).

Key Take-home: Screening for CAPN3 c.643_663del (p.Ser215_Gly221del) enables molecular confirmation of the autosomal dominant calpainopathy phenotype and informs clinical management.

References

  • Muscle & nerve • 2018 • Autosomal dominant calpainopathy due to heterozygous CAPN3 C.643_663del21. PMID:28881388

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

3 probands in independent AD families with segregation and initial functional data ([PMID:28881388])

Genetic Evidence

Limited

Recurrent c.643_663del in 3 unrelated families with co-segregation ([PMID:28881388])

Functional Evidence

Limited

Reduced calpain-3 expression on muscle Western blot supports haploinsufficiency ([PMID:28881388])