Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000187194 | SCV000240774 | uncertain significance | not provided | 2021-01-06 | criteria provided, single submitter | clinical testing | Observed in an individual with persistent developmental stuttering; however, additional information regarding the phenotype of the individual and information about parental testing were not provided and the authors concluded that CNTNAP2 variants were not associated with stuttering (Han et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24807205) |
Invitae | RCV000644710 | SCV000766413 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 627 of the CNTNAP2 protein (p.Val627Ile). This variant is present in population databases (rs147447659, gnomAD 0.05%). This missense change has been observed in individual(s) with specific language impairment (PMID: 24807205). ClinVar contains an entry for this variant (Variation ID: 205251). 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: "Probably Damaging"; 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. |
Ambry Genetics | RCV002314709 | SCV000847517 | uncertain significance | Inborn genetic diseases | 2018-10-19 | criteria provided, single submitter | clinical testing | The p.V627I variant (also known as c.1879G>A), located in coding exon 12 of the CNTNAP2 gene, results from a G to A substitution at nucleotide position 1879. The valine at codon 627 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly 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 variant remains unclear. |
New York Genome Center | RCV000644710 | SCV002097714 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2020-12-29 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271451 | SCV002556117 | uncertain significance | not specified | 2022-06-23 | criteria provided, single submitter | clinical testing | Variant summary: CNTNAP2 c.1879G>A (p.Val627Ile) results in a conservative amino acid change located in the Fibrinogen, alpha/beta/gamma chain, C-terminal globular domain (IPR002181) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.2e-05 in 282700 control chromosomes (gnomAD), predominantly at a frequency of 0.00048 within the African or African-American subpopulation in the gnomAD database. c.1879G>A has been reported in the literature in at least one individual affected with stuttering (Han_2014). This report does not provide unequivocal conclusions about association of the variant with Autism, Susceptibility 15. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters have assessed the variant since 2014: all classified the variant as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |