Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002012049 | SCV002227403 | uncertain significance | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 | 2022-06-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 582 of the MUSK protein (p.Gly582Arg). This variant is present in population databases (rs202126269, gnomAD 0.0009%). 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 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, |
RCV003130632 | SCV003811486 | uncertain significance | not provided | 2019-07-21 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004587265 | SCV005076561 | uncertain significance | not specified | 2024-04-24 | criteria provided, single submitter | clinical testing | Variant summary: MUSK c.1744G>A (p.Gly582Arg) results in a non-conservative amino acid change located in the Protein kinase domain (IPR000719) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 247162 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1744G>A has been reported in the literature in an individual affected with a Congenital myasthenic syndrome (Krenn_2023). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 36308527). ClinVar contains an entry for this variant (Variation ID: 1448049). Based on the evidence outlined above, the variant was classified as uncertain significance. |