ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.291C>A (p.Phe97Leu)

dbSNP: rs758058910
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Neuromuscular Diagnostic Laboratory, American University of Beirut Medical Center RCV000660877 SCV000778371 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2017-07-15 criteria provided, single submitter research c.291C>A (p.Phe97Leu) mutation was identified in a patient diagnosed with Limb girdle muscular dystrophy type 2A (LGMD2A). The diagnosis of LGMD2A was first suspected on the basis of a typical clinical localization of the muscle weakness and further confirmed by immunoblotting and molecular analysis. His family history is pertinent as his parents were first degree cousins, but none of his three younger brothers showed clinical evidence of similarly evolving dystrophic process.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004800511 SCV005423421 pathogenic Autosomal recessive limb-girdle muscular dystrophy 2024-10-04 criteria provided, single submitter clinical testing Variant summary: CAPN3 c.291C>A (p.Phe97Leu) results in a non-conservative amino acid change located in the Peptidase C2, calpain, catalytic domain (IPR001300) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 248996 control chromosomes. c.291C>A has been reported in the literature in the homozygous state in at least 2 individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive (example, El-Khoury_2019, Mojbafan_2020). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in complete loss of detectable calpain 3 protein (example, El-Khoury_2019). The following publications have been ascertained in the context of this evaluation (PMID: 30500922, 31937337). ClinVar contains an entry for this variant (Variation ID: 548137). Based on the evidence outlined above, the variant was classified as pathogenic.

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