Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001216477 | SCV001388276 | uncertain significance | Familial infantile myasthenia | 2022-08-03 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 945759). 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. 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 CHAT protein function. This variant has not been reported in the literature in individuals affected with CHAT-related conditions. This variant is present in population databases (rs754977595, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 256 of the CHAT protein (p.Thr256Ile). |