See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on variants detected in this gene.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

In individuals showing absent or severely reduced calpain-3 protein on immunoblot testing, the probability of identifying CAPN3 pathogenic variant(s) is about 84% [Fanin et al 2004].

In approximately 20%-30% of individuals with calpainopathy, only one CAPN3 pathogenic variant was found, possibly because the second pathogenic variant is located in genomic regions outside the coding exons (e.g., introns or promoter) or is a large genomic rearrangement [Fanin & Angelini 2015].

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

Large genomic rearrangements involving CAPN3 have been recognized as causative of calpainopathy [Richard et al 1999], including out-of-frame deletion of exons 2-8 [Joncourt et al 2003, Krahn et al 2007, Todorova et al 2007, Ginjaar et al 2008, Nascimbeni et al 2010], of exons 2-6 [Ginjaar et al 2008], or of the entire gene [Jaka et al 2014].