Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies
Gene: CAPN3
Comment on mode of inheritance: There is sufficient evidence (~15 unrelated cases with monoallelic inheritance) for updating the MOI of this gene from 'BIALLELIC, autosomal or pseudoautosomal' to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' at the next major review.Created: 16 Apr 2023, 9:57 p.m. | Last Modified: 16 Apr 2023, 9:57 p.m.
Panel Version: 4.11
As reviewed by Dmitrijs Rots (RadboudUMC), there are at least 15 unrelated families identified with monoallelic variants (six missense variants and 2 small in-frame deletions) in CAPN3 gene reported with limb girdle muscle dystrophy (LGMD) in literature. These variants are associated with a milder LGMD phenotype than patients identified with recessive variants, and some carriers only present with isolated hyperCKaemia. In general, the autosomal dominant variants have been associated with milder and later-onset phenotypes (disease onset at young adulthood at the earliest).
Both monoallelic and biallelic variants of this gene have been associated with relevant phenotypes in OMIM, but not in Gene2Phenotype.Created: 16 Apr 2023, 9:50 p.m. | Last Modified: 16 Apr 2023, 10:01 p.m.
Panel Version: 4.11
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes
Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600; Muscular dystrophy, limb-girdle, autosomal dominant 4, OMIM:618129
Publications
Description of novel 7 families with multiple affected individuals with segregating dominant CAPN3 variants. All missense, located in a specific region of protein (on 3D model) " in proximity to the calmodulin-binding site and are predicted to interfere with proteolytic activation."Created: 28 Nov 2021, 1:59 p.m. | Last Modified: 28 Nov 2021, 1:59 p.m.
Panel Version: 2.32
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
limb girdle muscle dystrophy
Publications
Comment on phenotypes: Previously:
Muscular dystrophy, limb-girdle, type 2A, 253600;Limb-Girdle Muscular Dystrophy, Recessive; Limb-girdle muscular dystrophyCreated: 13 Jul 2021, 10:41 a.m. | Last Modified: 13 Jul 2021, 10:41 a.m.
Panel Version: 2.19
Comment on publications: Added publication to support association with this phenotype.Created: 5 Oct 2020, 9:02 a.m. | Last Modified: 5 Oct 2020, 9:02 a.m.
Panel Version: 2.7
Listed as associated with Limb Girdle Muscular Dystrophy by Gene Advisor (June 2016), Steve Abbs
Created: 27 Jul 2016, 8:20 a.m.
Mode of inheritance for gene: CAPN3 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Tag Q2_23_MOI tag was added to gene: CAPN3.
Phenotypes for gene: CAPN3 were changed from Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600; Muscular dystrophy, limb-girdle, autosomal dominant 4, OMIM:618129 to Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600; Muscular dystrophy, limb-girdle, autosomal dominant 4, OMIM:618129
Phenotypes for gene: CAPN3 were changed from Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600; Muscular dystrophy, limb-girdle, autosomal dominant 4, OMIM:618129 to Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600; Muscular dystrophy, limb-girdle, autosomal dominant 4, OMIM:618129
Phenotypes for gene: CAPN3 were changed from Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600 to Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600; Muscular dystrophy, limb-girdle, autosomal dominant 4, OMIM:618129
Publications for gene: CAPN3 were set to http://www.ncbi.nlm.nih.gov/books/NBK1408/; 32994280
Phenotypes for gene: CAPN3 were changed from Muscular dystrophy, limb-girdle, type 2A, 253600; Limb-Girdle Muscular Dystrophy, Recessive; Limb-girdle muscular dystrophy to Muscular dystrophy, limb-girdle, autosomal recessive 1, OMIM:253600
Publications for gene: CAPN3 were set to http://www.ncbi.nlm.nih.gov/books/NBK1408/
Comments from Fiona Karet included. A Green review for each gene relevant for this panel on the Gene Advisor download has been included.
This gene has been classified as Green List (High Evidence).
Publications for CAPN3 were set to http://www.ncbi.nlm.nih.gov/books/NBK1408/
CAPN3 was added to Limb girdle muscular dystrophypanel. Sources: Eligibility statement prior genetic testing
Model of inheritance for gene CAPN3 was changed to BIALLELIC, autosomal or pseudoautosomal
CAPN3 was added to Limb girdle muscular dystrophypanel. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,,Illumina TruGenome Clinical Sequencing Services
Model of inheritance for gene CAPN3 was changed to BIALLELIC, autosomal or pseudoautosomal
CAPN3 was added to Limb girdle muscular dystrophypanel. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,,Illumina TruGenome Clinical Sequencing Services
Model of inheritance for gene CAPN3 was changed to BIALLELIC, autosomal or pseudoautosomal
CAPN3 was added to Limb girdle muscular dystrophypanel. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,,Illumina TruGenome Clinical Sequencing Services
CAPN3 was added to Limb girdle muscular dystrophypanel. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,,Illumina TruGenome Clinical Sequencing Services