Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000313599 | SCV000340082 | likely pathogenic | not provided | 2017-05-25 | criteria provided, single submitter | clinical testing | |
| Centre for Mendelian Genomics, |
RCV001196491 | SCV001367099 | likely pathogenic | Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2018-11-14 | criteria provided, single submitter | clinical testing | This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PM2,PM3,PP3,PP4. |
| Illumina Laboratory Services, |
RCV001249768 | SCV001423802 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2020-03-24 | criteria provided, single submitter | clinical testing | The CAPN3 c.1524G>A (p.Glu508Glu) is a synonymous splice region variant. The p.Glu508Glu variant has been reported in two studies in which it was identified in at least two individuals affected with limb girdle muscular dystrophy, in one in a homozygous state and in the other in a compound heterozygous state. In both patients, immunohistochemistry of tissue from muscle biopsy showed either neglible or absent Calpain-3 protein levels compared to normal controls (Guglieri et al. 2008). In addition, Milic et al. (2007), demonstrated that protein extracted from the muscle biopsy of a patient who carriend the p.Glu508Glu variant in a compound heterozygous state, did not have any Calpain-3 protein activity. The p.Glu508Glu variant is not found in the Genome Aggregation Database, in a region of good sequence coverage, so the variant is presumed to be rare. Based on the collective evidence and application of ACMG criteria, the p.Glu508Glu variant is classified as likely pathogenic for calpainopathy. |
| Invitae | RCV001249768 | SCV002172393 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2022-03-18 | criteria provided, single submitter | clinical testing | This sequence change affects codon 508 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 11, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with limb-girdle muscle weakness and/or limb-girdle muscular dystrophy (PMID: 16141003, 17994539, 32528171). ClinVar contains an entry for this variant (Variation ID: 286592). 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 may disrupt the consensus splice site. 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. |
| Baylor Genetics | RCV001196491 | SCV004213786 | likely pathogenic | Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2023-04-18 | criteria provided, single submitter | clinical testing |