ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.*534T>C

gnomAD frequency: 0.00016  dbSNP: rs772498665
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000376981 SCV000391059 uncertain significance Limb-girdle muscular dystrophy, recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000291826 SCV000391060 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV003225940 SCV003922316 uncertain significance Autosomal recessive limb-girdle muscular dystrophy 2023-05-02 criteria provided, single submitter curation The heterozygous c.*534T>C variant in CAPN3 was identified, in the compound heterozygous state with a likely pathogenic variant, in three siblings with limb-girdle muscular dystrophy (Broad Institute Rare Genomes Project). Trio genome analysis revealed that this variant was in trans with the likely pathogenic variant. This variant has not been previously reported in individuals with autosomal recessive limb-girdle muscular dystrophy 1 but has been identified in 0.01% (5/41444) of African/African American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs374665929). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID: 315905) and has been interpreted as a variant of uncertain significance by Illumina. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the c.*534T>C variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PM3, PP1 (Richards 2015).
Breakthrough Genomics, Breakthrough Genomics RCV004693213 SCV005193733 uncertain significance not provided criteria provided, single submitter not provided

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