Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001884213 | SCV002154691 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2021-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 183 of the MKS1 protein (p.Thr183Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs775805558, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with MKS1-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 not expected to disrupt MKS1 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. |