Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002638254 | SCV003520336 | uncertain significance | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 | 2022-03-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 3 of the MUSK protein (p.Glu3Lys). This variant is present in population databases (rs762340994, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MUSK-related conditions. 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 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. |
| Ambry Genetics | RCV002644151 | SCV003749229 | uncertain significance | Inborn genetic diseases | 2022-11-09 | criteria provided, single submitter | clinical testing | The c.7G>A (p.E3K) alteration is located in exon 1 (coding exon 1) of the MUSK gene. This alteration results from a G to A substitution at nucleotide position 7, causing the glutamic acid (E) at amino acid position 3 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |