Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000524008 | SCV000621013 | likely pathogenic | not provided | 2023-08-02 | criteria provided, single submitter | clinical testing | Reported previously in the compound heterozygous state and as a variant of uncertain significance in a fetus with fetal akinesia sequence (Vora et al., 2017); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25537362, 31974414, 28518170) |
Invitae | RCV001858023 | SCV002225729 | uncertain significance | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 | 2022-07-04 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 803 of the MUSK protein (p.Tyr803Cys). This variant is present in population databases (rs376837791, gnomAD 0.01%). This missense change has been observed in individual(s) with fetal akinesia deformation sequence (PMID: 28518170). ClinVar contains an entry for this variant (Variation ID: 452225). 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. |