Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002513709 | SCV003441304 | uncertain significance | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 | 2022-05-27 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with congenital myasthenic syndrome (PMID: 20371544). This variant is present in population databases (rs766640370, gnomAD 0.0009%). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 605 of the MUSK protein (p.Met605Ile). ClinVar contains an entry for this variant (Variation ID: 60521). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies have shown that this missense change affects MUSK function (PMID: 20371544). 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. |
OMIM | RCV000054417 | SCV000082894 | pathogenic | Congenital myasthenic syndrome 9 | 2010-06-15 | no assertion criteria provided | literature only |