Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000805470 | SCV000945427 | uncertain significance | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 | 2018-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glutamine at codon 158 and replaces serine with arginine at codon 159 of the MUSK protein (p.Asp158_Ser159delinsGluArg). The aspartic acid residue at codon 158 is highly conserved and there is a small physicochemical difference between aspartic acid and glutamine. The serine residue at codon 159 is moderately conserved and there is a moderate physicochemical difference between serine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MUSK-related conditions. Experimental studies and prediction algorithms are not available for this complex variant, and the functional significance of the affected amino acid(s) is currently unknown. In addition, algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of both missense changes (p.Asp158Glu: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"; p.Ser159Arg: SIFT: "Tolerated";PolyPhen-2: "Not Available"; Align-GVGD: Class C0"). 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. |