Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000413099 | SCV000490625 | uncertain significance | not specified | 2016-09-23 | criteria provided, single submitter | clinical testing | The R767H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R767H variant was not observed with any significant frequency in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The R767H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV000701606 | SCV000830416 | uncertain significance | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 | 2022-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 767 of the MUSK protein (p.Arg767His). This variant is present in population databases (rs370079610, gnomAD 0.006%). 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: 372415). 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. |
| Ambry Genetics | RCV004022154 | SCV004935701 | uncertain significance | Inborn genetic diseases | 2022-05-27 | criteria provided, single submitter | clinical testing | The c.2300G>A (p.R767H) alteration is located in exon 15 (coding exon 15) of the MUSK gene. This alteration results from a G to A substitution at nucleotide position 2300, causing the arginine (R) at amino acid position 767 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |