Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000187190 | SCV000240770 | uncertain significance | not provided | 2014-09-12 | criteria provided, single submitter | clinical testing | p.Ser570Trp (TCG>TGG): c.1709 C>G in exon 11 of the CNTNAP2 gene (NM_014141.5). The S570W variant has not been published as a mutation, nor has it been reported as a benign polymorphism 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 S570W 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 through mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense mutations in nearby residues have notbeen reported. 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 |
RCV001369580 | SCV001566022 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2020-03-20 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with tryptophan at codon 570 of the CNTNAP2 protein (p.Ser570Trp). The serine residue is moderately conserved and there is a large physicochemical difference between serine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CNTNAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 205247). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |