Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003517505 | SCV004274947 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2023-07-28 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 32646536). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 169 of the CAPN3 protein (p.Arg169His). This variant is present in population databases (no rsID available, gnomAD 0.006%). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CAPN3 protein function. This variant disrupts the p.Arg169 amino acid residue in CAPN3. Other variant(s) that disrupt this residue have been observed in individuals with CAPN3-related conditions (Invitae), which suggests that this may be a clinically significant amino acid residue. 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 | RCV003460310 | SCV004213742 | likely pathogenic | Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2023-08-01 | flagged submission | clinical testing |