Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000187210 | SCV000240792 | uncertain significance | not provided | 2012-09-14 | criteria provided, single submitter | clinical testing | p.Pro804Arg (CCA>CGA):c.2411 C>G in exon 16 of the CNTNAP2 gene (NM_014141.4). The Pro804Arg 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 Pro804Arg in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as a uncharged, non-polar Proline residue is replaced by a positively charged Arginine residue, and the loss of a bulky Proline may alter the secondary structure of the CNTNAP2 protein. However, Pro804Arg alters a position in the third Laminin G-like domain of the protein that is not conserved across species. While one in silico model predicts it may be damaging to protein structure/function, other models predict it is likely not pathogenic. Therefore, based on the currently available information, it is unclear whether Pro804Arg is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
Invitae | RCV002517856 | SCV003280194 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2022-02-23 | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 205266). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. This variant is present in population databases (rs796052376, gnomAD 0.0009%). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 804 of the CNTNAP2 protein (p.Pro804Arg). |