ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.2329A>G (p.Ile777Val)

gnomAD frequency: 0.00008  dbSNP: rs149969786
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV000644992 SCV000221429 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A criteria provided, single submitter research Downgraded to VUS based on high updated frequency
Labcorp Genetics (formerly Invitae), Labcorp RCV000644992 SCV000766728 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2024-10-17 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 777 of the CAPN3 protein (p.Ile777Val). This variant is present in population databases (rs149969786, gnomAD 0.02%). This missense change has been observed in individual(s) with distal posterior limb muscle atrophy and weakness (PMID: 27671536). ClinVar contains an entry for this variant (Variation ID: 191056). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CAPN3 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl RCV000644992 SCV000800486 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2017-01-03 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000171232 SCV000860850 uncertain significance not provided 2018-04-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005055670 SCV005726765 uncertain significance not specified 2024-11-11 criteria provided, single submitter clinical testing Variant summary: CAPN3 c.2329A>G (p.Ile777Val) results in a conservative amino acid change located in the Calcium-activated neutral domain (IPR029531) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251414 control chromosomes. c.2329A>G has been reported in the literature in the homozygouse state in at least one individual affected with distal posterior limb muscle atrophy and weakness (Monies_2016). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 27671536). ClinVar contains an entry for this variant (Variation ID: 191056). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Natera, Inc. RCV000644992 SCV001456377 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2020-09-16 no assertion criteria provided clinical testing

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