Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001337624 | SCV001531232 | uncertain significance | Bethlem myopathy 1A | 2023-12-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2811 of the COL6A3 protein (p.Arg2811Cys). This variant is present in population databases (rs371361651, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of congenital muscular dystrophy (PMID: 28688748). ClinVar contains an entry for this variant (Variation ID: 1034842). 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 expected to disrupt COL6A3 protein function with a positive predictive value of 80%. 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. |
| Gene |
RCV001664838 | SCV001874244 | uncertain significance | not provided | 2021-08-27 | criteria provided, single submitter | clinical testing | Reported in the compound heterozygous state in an individual with a congenital muscular dystrophy in published literature; however, specific clinical information and details about the second variant were not provided (Sframeli et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 28688748) |