Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000497317 | SCV000590573 | uncertain significance | not provided | 2017-06-21 | criteria provided, single submitter | clinical testing | The G186A variant in the MUSK gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The G186A variant is observed in 3/11576 (0.026%) alleles from individuals of Latino background in the ExAC dataset (Lek et al., 2016). The G186A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G186A as a variant of uncertain significance. |
Invitae | RCV000700783 | SCV000829554 | uncertain significance | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 186 of the MUSK protein (p.Gly186Ala). This variant is present in population databases (rs373304727, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with MUSK-related conditions. ClinVar contains an entry for this variant (Variation ID: 432807). 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 MUSK protein function. 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. |
Revvity Omics, |
RCV000497317 | SCV003817126 | uncertain significance | not provided | 2021-11-24 | criteria provided, single submitter | clinical testing |