Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000520159 | SCV000618813 | uncertain significance | not provided | 2017-06-30 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the TMEM237 gene. The H222R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The H222R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the H222R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties and this substitution occurs at a position that is not conserved. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV002525159 | SCV003477783 | uncertain significance | Joubert syndrome 14 | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 222 of the TMEM237 protein (p.His222Arg). This variant is present in population databases (rs749330370, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TMEM237-related conditions. ClinVar contains an entry for this variant (Variation ID: 450257). 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 TMEM237 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. |