Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001225866 | SCV001398160 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with asparagine at codon 831 of the CNTNAP2 protein (p.Thr831Asn). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and asparagine. This variant is present in population databases (rs138344590, ExAC 0.003%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
Gene |
RCV002284475 | SCV002574623 | uncertain significance | not provided | 2022-09-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002429959 | SCV002740885 | uncertain significance | Inborn genetic diseases | 2017-11-17 | criteria provided, single submitter | clinical testing | The p.T831N variant (also known as c.2492C>A), located in coding exon 16 of the CNTNAP2 gene, results from a C to A substitution at nucleotide position 2492. The threonine at codon 831 is replaced by asparagine, an amino acid with similar properties. This amino acid position is not well 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. |