Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000201022 | SCV000255665 | pathogenic | not provided | 2018-08-27 | criteria provided, single submitter | clinical testing | The variant results in a shift of the reading frame, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and not found in general population data. Moderate co-segregation with disease. |
| Broad Center for Mendelian Genomics, |
RCV001004958 | SCV001164493 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2018-12-03 | criteria provided, single submitter | research | The heterozygous p.Ile162SerfsTer17 variant in CAPN3 was identified by our study in the compound heterozygous state, with another pathogenic variant, in one individual with limb-girdle muscular dystrophy (LGMD). The presence of this variant in combination with a pathogenic variant and in an individual with LGMD increases the likelihood that the p.Ile162SerfsTer17 variant is pathogenic. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 162 and leads to a premature termination codon 17 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the CAPN3 gene is an established disease mechanism in autosomal recessive LGMD. In summary, this variant meets criteria to be classified as pathogenic for LGMD in an autosomal recessive manner based on the predicted impact of the variant and the presence of another pathogenic variant in one individual with LGMD. ACMG/AMP Criteria applied: PM2, PVS1, PM3 (Richards 2015). |
| Labcorp Genetics |
RCV001004958 | SCV002237073 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2023-10-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ile162Serfs*17) in the CAPN3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CAPN3 are known to be pathogenic (PMID: 10330340, 15689361). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with limb girdle muscular dystrophy type 2 (PMID: 16650086). ClinVar contains an entry for this variant (Variation ID: 217156). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003462348 | SCV004213761 | pathogenic | Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2023-06-19 | criteria provided, single submitter | clinical testing |