Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001034994 | SCV001198299 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2019-03-11 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with isoleucine at codon 376 of the CNTNAP2 protein (p.Val376Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. 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. 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. |
Gene |
RCV001805979 | SCV002050665 | uncertain significance | not provided | 2021-06-28 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); 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; This variant is associated with the following publications: (PMID: 27535533) |
Ambry Genetics | RCV003372938 | SCV004095463 | uncertain significance | Inborn genetic diseases | 2023-08-28 | criteria provided, single submitter | clinical testing | The c.1126G>A (p.V376I) alteration is located in exon 8 (coding exon 8) of the CNTNAP2 gene. This alteration results from a G to A substitution at nucleotide position 1126, causing the valine (V) at amino acid position 376 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |