ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.309G>A (p.Pro103=)

gnomAD frequency: 0.00001  dbSNP: rs376146681
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667856 SCV000792367 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2017-06-19 criteria provided, single submitter clinical testing
GeneDx RCV001756131 SCV001985434 uncertain significance not provided 2020-03-11 criteria provided, single submitter clinical testing Reported along with a pathogenic variant in CAPN3 in a patient with LGMD in published literature; however, segregation information was not provided (Ten Dam et al., 2019); Reported along with a second variant in CAPN3 in a patient with LGMD2A in published literature; however, segregation information was not provided (Blazquez et al., 2008); In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 18563459, 30919934)
Labcorp Genetics (formerly Invitae), Labcorp RCV000667856 SCV003442814 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2024-10-30 criteria provided, single submitter clinical testing This sequence change affects codon 103 of the CAPN3 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CAPN3 protein. This variant also falls at the last nucleotide of exon 1, which is part of the consensus splice site for this exon. This variant is present in population databases (rs376146681, gnomAD 0.007%). This variant has been observed in individuals with autosomal recessive Limb-Girdle Muscular Dystrophy (PMID: 18563459, 30919934). ClinVar contains an entry for this variant (Variation ID: 552569). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.

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