Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000644733 | SCV000766436 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2022-08-21 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 545 of the CNTNAP2 protein (p.Ala545Val). This variant is present in population databases (rs771772546, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 536331). 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 |
RCV001552841 | SCV001773608 | uncertain significance | not provided | 2023-10-04 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 37543562, 32381728) |
Foundation for Research in Genetics and Endocrinology, |
RCV001730703 | SCV001960906 | likely pathogenic | Autism, susceptibility to, 15 | 2021-05-11 | criteria provided, single submitter | research | A heterozygous missense variation in exon 10 of the CNTNAP2 gene that results in the amino acid substitution of Valine for Alanine at codon 545 was detected. The observed variant c.1634C>T (p.Val545Ala) has not been reported in the 1000 genomes but has a minor allele frequency of 0.006% in the gnomAD databases. The in silico prediction of the variant are damaging by SIFT, LRT and MutationTaster2. The reference codon is conserved across species. Segregation analysis showed the variant to be de novo in origin. In summary, the variant meets our criteria to be classified as a likely pathogenic variant. |
Ambry Genetics | RCV002397245 | SCV002707625 | uncertain significance | Inborn genetic diseases | 2017-12-18 | criteria provided, single submitter | clinical testing | The p.A545V variant (also known as c.1634C>T), located in coding exon 10 of the CNTNAP2 gene, results from a C to T substitution at nucleotide position 1634. The alanine at codon 545 is replaced by valine, an amino acid with similar properties. This amino acid position is 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. |