Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000485815 | SCV000566236 | uncertain significance | not provided | 2016-06-30 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CNTNAP2 gene. The K331N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The K331N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with CNTNAP2-related disorder (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV001320461 | SCV001511248 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2020-08-24 | criteria provided, single submitter | clinical testing | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CNTNAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 418866). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with asparagine at codon 331 of the CNTNAP2 protein (p.Lys331Asn). The lysine residue is weakly conserved and there is a moderate physicochemical difference between lysine and asparagine. |