ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.377T>C (p.Leu126Pro)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Medical Molecular Genetics Department, National Research Center RCV004780044 SCV005392720 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2024-06-11 criteria provided, single submitter clinical testing By applying ACMG guidelines: According to insilico studies, the variant is classified as deleterious (PP3),our study patient’s clinical phenotype is typically correlated to the disease (PP4), it showed an extremely low frequency in gnomAD population databases (PS4) additionally, by segregation analysis: the affected proband sibling showed the same variant at the homozygous form the healthy sibling showed the wild genotype for both alleles and parents showed the heterozygous status (PP1). according to this data it is considered as likely pathogenic by ACMG guidlines.
Labcorp Genetics (formerly Invitae), Labcorp RCV004780044 SCV005777762 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2024-05-02 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 126 of the CAPN3 protein (p.Leu126Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with limb-girdle weakness (PMID: 32528171). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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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