Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000187211 | SCV000240793 | uncertain significance | not provided | 2012-10-18 | criteria provided, single submitter | clinical testing | p.Asn839Ser (AAT>AGT):c.2516 A>G in exon 16 of the CNTNAP2 gene (NM_014141.4). The Asn839Ser missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Asn839ser in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. Asn839Ser alters a highly conserved position in the laminin G domain of the CNTNAP2 protein. However, the amino acid substitution is conservative, as both Asparagine and Serine are uncharged, polar amino acid residues. In addition, while several in silico algorithms predict Asn839Ser may be pathogenic to the structure/function of the protein, other algorithms predict it is likely benign. Therefore, based on the currently available information, it is unclear whether Asn839Ser is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
| Invitae | RCV001211499 | SCV001383040 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2020-02-07 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CNTNAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 205267). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with serine at codon 839 of the CNTNAP2 protein (p.Asn839Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. |