Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002317495 | SCV000850894 | uncertain significance | Inborn genetic diseases | 2017-05-26 | criteria provided, single submitter | clinical testing | The p.A667T variant (also known as c.1999G>A), located in coding exon 13 of the CNTNAP2 gene, results from a G to A substitution at nucleotide position 1999. The alanine at codon 667 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000793457 | SCV000932809 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2022-04-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 667 of the CNTNAP2 protein (p.Ala667Thr). This variant is present in population databases (rs374920791, gnomAD 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: 589782). 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: "Benign"; 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. |