Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000187214 | SCV000240796 | uncertain significance | not provided | 2014-02-20 | criteria provided, single submitter | clinical testing | p.Asn878Asp (AAC>GAC): c.2632 A>G in exon 17 of the CNTNAP2 gene (NM_014141.5). The Asn878Asp variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The Asn878Asp 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 across species in the laminin G-Like 3 domain of the CNTNAP2 protein. However, 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 mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
Labcorp Genetics |
RCV001852449 | SCV002115725 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2024-05-15 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 878 of the CNTNAP2 protein (p.Asn878Asp). This variant is present in population databases (rs375538831, gnomAD 0.007%). 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: 205269). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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. |