Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000485810 | SCV000573060 | uncertain significance | not provided | 2017-02-03 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CNTNAP2 gene. The P1097S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P1097S 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. The P1097S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with CNTNAP2-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Fulgent Genetics, |
RCV000765939 | SCV000897359 | uncertain significance | Autism, susceptibility to, 15; Cortical dysplasia-focal epilepsy syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001321910 | SCV001512761 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 1097 of the CNTNAP2 protein (p.Pro1097Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs200823464, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 423369). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. |