Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000688431 | SCV000816041 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with threonine at codon 1173 of the CNTNAP2 protein (p.Pro1173Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs772569737, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. 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. |
| Ambry Genetics | RCV002458210 | SCV002613226 | uncertain significance | Inborn genetic diseases | 2018-01-17 | criteria provided, single submitter | clinical testing | The p.P1173T variant (also known as c.3517C>A), located in coding exon 22 of the CNTNAP2 gene, results from a C to A substitution at nucleotide position 3517. The proline at codon 1173 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |